Journal articles on the topic 'Kappa free light chains'
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1
Schwenkenbecher, Philipp, Franz Konen, Ulrich Wurster, Konstantin Jendretzky, Stefan Gingele, Kurt-Wolfram Sühs, Refik Pul, Torsten Witte, Martin Stangel, and Thomas Skripuletz. "The Persisting Significance of Oligoclonal Bands in the Dawning Era of Kappa Free Light Chains for the Diagnosis of Multiple Sclerosis." International Journal of Molecular Sciences 19, no. 12 (November 29, 2018): 3796. http://dx.doi.org/10.3390/ijms19123796.
Abstract:
The latest revision of the McDonald criteria of 2017 considers the evidence of an intrathecal immunoglobulin (IgG) synthesis as a diagnostic criterion for dissemination in time in multiple sclerosis. While the detection of oligoclonal bands is considered as the gold standard, determination of kappa free light chains might be a promising tool as a less technically demanding and cost saving method. However, data on the direct comparison between kappa free light chains and oligoclonal bands are limited and no study to date has used the highly sensitive method of polyacrylamide gels with consecutive silver staining for the demonstration of oligoclonal bands. Furthermore, the impact of the revised McDonald criteria of 2017 on the role of kappa free light chains as a biomarker has not been investigated. Nephelometry was used to determine kappa free light chains in cerebrospinal fluid (CSF) and serum from 149 patients with their first demyelinating event between 2010 and 2015. Clinical data, kappa free light chains, and oligoclonal band status were compared at the time of initial diagnosis and after follow-up to identify converters from clinically isolated syndrome to multiple sclerosis. An elevated kappa free light chain index (>5.9) was found in 79/83 patients (95%) with multiple sclerosis diagnosed at baseline, slightly less frequent than oligoclonal bands (98.8%). 18/25 (72%) patients who converted from clinically isolated syndrome to multiple sclerosis showed an elevated kappa free light chain index compared to 20/25 (80%) patients with positive oligoclonal bands. In patients with stable clinically isolated syndrome 7/41 (17%) displayed an elevated kappa free light chain index against 11/41 (27%) oligoclonal band positive patients. Only two patients with stable clinically isolated syndrome showed an elevated kappa free light chain index but were oligoclonal bands negative. In conclusion, determination of the kappa free light chain index is a promising diagnostic approach to assess intrathecal immunoglobulin synthesis in multiple sclerosis. Nevertheless, oligoclonal bands are highly prevalent in multiple sclerosis and can detect an intrathecal synthesis of IgG even when the kappa free light chain index is below the threshold. We consider sequential use of both methods as reasonable.
2
Dul, J. L., S. Aviel, J. Melnick, and Y. Argon. "Ig light chains are secreted predominantly as monomers." Journal of Immunology 157, no. 7 (October 1, 1996): 2969–75. http://dx.doi.org/10.4049/jimmunol.157.7.2969.
Abstract:
Abstract Ig light (L) chains are secreted not only as part of assembled Ab molecules, but also as free L chains, the latter process being involved in the pathology of several diseases. The secretion competence of free L chains distinguishes them from free subunits of other oligomeric proteins, which are usually retained intracellularly. We used several techniques to test the idea that secretion of free L chains is dependent on dimerization. Coexpression of pairs of L chains, differing in only one amino acid, which alters the secretory phenotype, shows that these L chains behave independently: the wild-type chains are secreted, whereas the mutants are retained intracellularly. A survey of kappa- or lambda-producing cell lines by nonreducing gel electrophoresis shows that a negligible fraction of these L chains exists as disulfide-bonded dimers. Moreover, chemical cross-linking and density gradient centrifugation demonstrate that there is no significant pool of noncovalent L chain dimers. Noncovalent heterodimers can be detected readily between a kappa-chain and a chimera consisting of a heavy chain variable domain linked to the kappa-chain constant domain. This confirms that noncovalent L chain homodimers would have been detected if they were present. These findings about the association state of free L chains are independent of the host cell, as they are observed in both myeloma cells and COS fibroblasts. We conclude that L chain dimerization is a rare event that neither facilitates secretion nor is required for it.
3
Ambrosino, D. M., M. V. Kanchana, N. R. Delaney, and R. W. Finberg. "Human B cells secrete predominantly lambda L chains in the absence of H chain expression." Journal of Immunology 146, no. 2 (January 15, 1991): 599–602. http://dx.doi.org/10.4049/jimmunol.146.2.599.
Abstract:
Abstract Ig H and L chains are independently assembled in B cells and then secreted together as a functional protein. H chains cannot be secreted without assembly to L chains; however, L chains can be secreted in the absence of H chains by both mice and human cells. To examine the influence of H chain expression on human L chain isotype selection (kappa or lambda), we compared the kappa/lambda ratio of L chains unassociated with H chains (free L chains) to the kappa/lambda ratio of L chains associated with H chains. Culture supernatants of human splenocytes were assayed for kappa and lambda L chains. Free L chains were the predominant form of L chains detected in unstimulated cultures, accounting for 68 to 70% of the total. This was in contrast to the minor proportion that free L chains represented (less than 20%) in cultures stimulated with PWM or LPS (p less than 0.01). Furthermore, the kappa/lambda ratio of light chains detected in unstimulated cultures was 0.5 as compared to 1.3 for PWM stimulated cultures (p = 0.0001). To demonstrate that the decreased kappa/lambda ratio of L chains in the supernatants of cultures of unstimulated B cells was due to free L chains, we measured the kappa/lambda ratio of IgG and IgM-associated L chains. In both the stimulated and unstimulated cultures, the kappa/lambda ratio of L chains associated with H chains was greater than the ratio determined for free L chains. Free L chains were shown to be predominantly lambda as compared to the predominantly kappa phenotype of L chains associated with H chains. Thus absence of H chain expression affects selection of L chain isotypes secreted by human B cells.
4
Richter, Alex G., Stephen Harding, Aarnoud Huissoon, Mark Drayson, and Guy Pratt. "Multiple Myeloma with Monoclonal Free IgG3 Heavy Chains and Free Kappa Light Chains." Acta Haematologica 123, no. 3 (2010): 158–61. http://dx.doi.org/10.1159/000292899.
5
Arneth, Borros, and Jörg Kraus. "The Use of Kappa Free Light Chains to Diagnose Multiple Sclerosis." Medicina 58, no. 11 (October 24, 2022): 1512. http://dx.doi.org/10.3390/medicina58111512.
Abstract:
Background: The positive implications of using free light chains in diagnosing multiple sclerosis have increasingly gained considerable interest in medical research and the scientific community. It is often presumed that free light chains, particularly kappa and lambda free light chains, are of practical use and are associated with a higher probability of obtaining positive results compared to oligoclonal bands. The primary purpose of the current paper was to conduct a systematic review to assess the up-to-date methods for diagnosing multiple sclerosis using kappa and lambda free light chains. Method: An organized literature search was performed across four electronic sources, including Google Scholar, Web of Science, Embase, and MEDLINE. The sources analyzed in this systematic review and meta-analysis comprise randomized clinical trials, prospective cohort studies, retrospective studies, controlled clinical trials, and systematic reviews. Results: The review contains 116 reports that includes 1204 participants. The final selection includes a vast array of preexisting literature concerning the study topic: 35 randomized clinical trials, 21 prospective cohort studies, 19 retrospective studies, 22 controlled clinical trials, and 13 systematic reviews. Discussion: The incorporated literature sources provided integral insights into the benefits of free light chain diagnostics for multiple sclerosis. It was also evident that the use of free light chains in the diagnosis of clinically isolated syndrome (CIS) and multiple sclerosis is relatively fast and inexpensive in comparison to other conventional state-of-the-art diagnostic methods, e.g., using oligoclonal bands (OCBs).
6
Ramsden, DB. "Multiple sclerosis: assay of free immunoglobulin light chains." Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 54, no. 1 (September 28, 2016): 5–13. http://dx.doi.org/10.1177/0004563216652175.
Abstract:
Over the past five years, a number of papers have appeared describing the assay of free immunoglobulin light chains in cerebrospinal fluid to assist in the diagnosis of multiple sclerosis. The assay of kappa free immunoglobulin chains is being advocated as a technically simpler and cheaper quantitative alternative to the qualitative detection of oligoclonal bands. This article reviews the analytical and clinical characteristics of these immunoglobulin free light chain assays and places them in their historical context and possible future developments.
7
Vinayek, Namita, Goetz H. Kloecker, and Beth C. Riley. "Multiple Myeloma with Secretory and Non-Secretory Biclonal Gammopathy." Blood 118, no. 21 (November 18, 2011): 5092. http://dx.doi.org/10.1182/blood.v118.21.5092.5092.
Abstract:
Abstract Abstract 5092 Multiple myeloma (MM) accounts for 10 % of hematological malignancies. MM with biclonal gammopathy are rare and seen in 1 % of all MM cases. In 99% of the MM cases, paraproteins are secreted in the serum and/or urine, in the remaining 1% the paraproteins are synthesized but not secreted. Only 2 % of patients are younger than 40 years of age. We report a 36 year old African American female who presented with diffuse lytic lesions. Serum electrophoresis (SPEP) revealed IgG kappa M protein of 3.8 g/dl and a IgG Kappa M spike of 2.6 mg/dl. Free light chains (SFLC) revealed elevated free kappa chains of 500 mg/dl, elevated free lambda chains of 928 mg/dl and K/L ratio of 0.55. Urine protein UPEP showed an M spike of IgG kappa and free kappa light chains. The B2 microglobulin was 26.8 mg/dl. Patient's recent T10 Bone biopsy done at outside hospital had a near complete replacement of the marrow by plasma cells which were biclonal plasma cells by IHC, one kappa restricted and one lambda restricted. Since the IFE showed only a single IgG kappa M protein spike, the lambda plasma clone was apparently non-secretory. Treatment was started with cyclophosphamide, bortezomib and dexamethasone. After 22 days of treatment, the M protein has decreased 1.39 mg/dl. A repeat SFLC also shows further decline in free kappa light chains. As the IFE showed one gamma M spike and bone biopsy had two clonal plasma cells it was concluded that one of the neoplasms is nonsecretory. Although the elevated lambda free light chain in the serum is now does point towards a second plasma cell neoplasm. Biclonal gammopathy is rare and accounts for 1% of all MM cases. To our knowledge, this is the first reported case of a biclonal, secretory and nonsecretory, gammopathy Disclosures: No relevant conflicts of interest to declare.
8
Abbi, Kamal Kant Singh, Guido J. Tricot, Margarida Silverman, Kalyan Nadiminti, and Matthew Krasowski. "Potential Pitfalls of Serum Free Light Chain Analysis to Assess Treatment Response for Multiple Myeloma." Blood 126, no. 23 (December 3, 2015): 5308. http://dx.doi.org/10.1182/blood.v126.23.5308.5308.
Abstract:
Abstract Background The serum free light chain (FLC test) allows measurement of low concentrations of FLC. Post-transplantation, especially after tandem autologous transplants and consolidation therapy, the immune system is often extremely suppressed and its recovery is disorganized. Patients and Methods This study was limited to patients with multiple myeloma, plasma cell leukemia and amyloidosis, who received autologous transplantation and consolidation therapy at the University of Iowa Hospitals and clinics. Most of these patients had already received some form of induction therapy with IMIDs or proteasome inhibitors or in combination. They then proceeded with a cycle of D-PACE followed by one or two autologous transplants. The preparative regimen for virtually all patients was VDT-MEL. Post-transplantation, most of the patients received consolidation therapy with VTD the first year and either VCD or Revlimid/dexamethasone for second year. Thereafter, all myeloma therapy was halted. Serum free light chains were measured with polyclonal FLC antisera according to Freelite, Binding site, UK. The kappa/ lambda ratio was calculated. Results In total 142 patients were evaluated; 12 % (17/142) of patients were found to have abnormal light chains ratio but no other evidence of active disease, including negative serum M-protein, serum IFE, urine M-protein and urine IFE. In addition, bone marrows showed no evidence of clonal plasma cells by both 10-color flow cytometry and FISH analysis of CD138 selected plasma cells; both methods have a sensitivity of ≥ 10-4. The κ/λ ratio was abnormal due to increase/decrease in the same light chain as the M- protein in 11/17 patients; 6/17 patients had abnormal κ/λ ratio due to increase in the opposite light chain as the M- protein (Table 1) Table 1. Patient with abnormal light chains due changes in Involved light chain levels Age Gender M protein/Light chain Transplant M protein Abnormal light chain Immunofixation Elevated or decreased Duration of abnormal ratio 64 Male IgG Kappa Tandem 0.0 Kappa Negative Elevated 2 weeks 58 Female IgA Kappa Tandem 0.0 Kappa Negative Elevated 4 weeks 46 Female Kappa Tandem 0.0 Kappa Negative Elevated 4 weeks 58 Male IgG Kappa Tandem 0.0 Kappa Negative Elevated 20 weeks 55 Male IgG Kappa Tandem 0.0 Kappa Negative Elevated 4 weeks 60 Male IgG Kappa Tandem 0.0 Kappa Negative Elevated One week 60 Female IgA Kappa Single 0.0 Kappa Negative Elevated 8 weeks 68 Female IgG Kappa Single 0.0 Kappa Negative Elevated 26 weeks 42 Male kappa Tandem 0.0 Kappa Negative Elevated One week 67 Male Kappa Single 0.0 Kappa Negative Decreased 3 weeks 68 Male IgG Kappa Single 0.0 Kappa Negative Elevated 8 weeks Patient with abnormal light chain ratio due to changes in the opposite light chain levels 53 Female IgG Lambda Tandem 0.0 Kappa Negative Elevated 2 weeks 62 Female IgA lambda Tandem 0.0 Kappa Negative Elevated 6 weeks 50 Male Lambda Single 0.0 Kappa Negative Elevated One week 60 Male IgG Lambda Tandem 0.0 Kappa Negative Elevated 100 weeks 68 Female IgA Lambda Single 0.0 Kappa Negative Elevated 8 weeks 68 Male lambda Single 0.0 Kappa Negative Elevated 4 weeks Conclusions According to the IMWG uniform response criteria, patients achieving CR for whom the involved FLC reduced sufficiently to normalize the FLC ratio (range, 0.26 to 1.65) in the absence of monoclonal BMPCs as assessed by immunohistochemistry or immunofluorescence are considered to have achieved stringent CR. However, patients can be in stringent complete remission with abnormal k/l ratios if 1) the ratio is abnormal because the non-involved free light chain is elevated while the involved free light chain is normal; 2) the ratio is abnormal because involved light chain is elevated, with no other evidence of disease, including multicolor flow cytometry and FISH analysis on selected plasma cells of the bone marrow and imaging by MRI and/or PET-CT scan. This occurred in > 10% of patients. It should be noted that the FLC causing the abnormal k/l ratio was always kappa. The IMWG criteria should be adjusted these potential pitfalls. Disclosures No relevant conflicts of interest to declare.
9
Rudick, Richard A., Adam Pallant, Jean M. Bidlack, and Robert M. Herndon. "Free kappa light chains in multiple sclerosis spinal fluid." Annals of Neurology 20, no. 1 (July 1986): 63–69. http://dx.doi.org/10.1002/ana.410200111.
10
Pratt, G., A. Richter, A. Huisoon, M. Drayson, and S. Harding. "A177 Multiple Myeloma with Monoclonal Free IgG3 Heavy Chains and Free Kappa Light Chains." Clinical Lymphoma and Myeloma 9 (February 2009): S30—S31. http://dx.doi.org/10.1016/s1557-9190(11)70494-2.
11
Lee, Won S., and Gurmukh Singh. "Serum Free Light Chain Assay in Monoclonal Gammopathic Manifestations." Laboratory Medicine 50, no. 4 (April 8, 2019): 381–89. http://dx.doi.org/10.1093/labmed/lmz007.
Abstract:
Abstract Background Serum free light chain assay is used in the diagnosis and monitoring of monoclonal gammopathic manifestations. For the kappa (κ)/lambda (λ) ratio, there is a 36% false-positive rate in patients without monoclonal gammopathic manifestations and a 30% false-negative rate in patients with monoclonal gammopathic manifestations. This study was undertaken to address the higher false-negative rate in λ chain–associated monoclonal lesions. Methods Results of serum protein electrophoresis, serum immunofixation electrophoresis, and serum free light chain assays were reviewed retrospectively. The results for serum free light chains in cases of intact immunoglobulin monoclonal gammopathic manifestations only were analyzed. Results Concentrations of involved serum free light chains were significantly higher in κ chain–associated lesions than in λ chain–associated lesions. The concentration of uninvolved light chains was significantly higher in λ chain–associated lesions. Conclusions κ light chains are present in significantly greater abundance than are λ chains in their respective monoclonal lesions. Moreover, κ and λ light-chain levels are not comparable for similar quantitative levels of monoclonal immunoglobulins. The findings warrant a reconsideration of the role of serum free light chain concentrations and involved to uninvolved serum free light chain ratio in designation of myeloma-defining conditions and other diagnostic criteria based on serum free light chain assay.
12
Richter, Alex G., Stephen Harding, Steve Rimmer, Guy Pratt, Aarnoud Huissoon, and Mark Drayson. "Biclonal Multiple Myeloma with Monoclonal Free IgG3 Heavy Chain and kappa Free Light Chains." Blood 110, no. 11 (November 16, 2007): 4768. http://dx.doi.org/10.1182/blood.v110.11.4768.4768.
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Abstract Background: Heavy chain disease (HCD) is a rare lymphoproliferative disorder characterized by a monoclonal heavy chain (HC) unattached to a light chain (LC). IgGHCD or γHCD typically presents as a lymphoproliferative disorder with lymphadenopathy and hepatosplenomegaly. Myeloma has been described associated with γHCD but only with a second intact Ig paraprotein. This report describes a unique presentation of multiple myeloma with monoclonal free γ3HC and kappa free light chains. Case: A 34 year old gentleman presented with mild persistent neutropenia following two episodes of pneumonia, 18 months previously. He admitted to persistent night sweats but no other significant history. Baseline investigations revealed a mild anaemia, neutropenia and a large IgG paraprotein with no associated light chain. Bone marrow aspirate and trephine confirmed myeloma. The patient was treated with cyclophosphamide, thalidomide and dexamethasone and has had a very good partial remission. He is awaiting a sibling allogeneic peripheral blood stem cell transplant. Investigations and results: Serum Electrophoresis confirmed a large IgG paraprotein (23g/l) with no associated light chain in the serum and identified as γ3 subclass by radial immunodiffusion. Western blot showed the γ3HC was truncated with a large deletion. Markedly elevated free kappa (κ) LC (503.58 mg/l [3.30–19.4]) were found in the serum with gross skewing of the kappa/lambda ratio. Urine electrophoresis revealed separate γHC and κ LC paraproteins. Western blot of the fractionated urine protein demonstrated different sized κLC aggregates. Flow cytometry of the marrow aspirate revealed an unusual staining pattern; CD5,19,38,45+ve and CD20,22,23,34,56,138 –ve plasma cells. Cytoplasmic staining revealed 2 distinct populations of plasma cells, the first producing γ3HC and the second only free κLC. Cytogenetics and FISH analysis for 14q, p53 and c-myc abnormalities were normal. Discussion: This is the first description of a Biclonal Myeloma with separate plasma cell populations producing γ3HC and κLC paraproteins. The biclonality confirms the free HC occurs as a result of abnormal synthesis not cleavage. The clinical and immunological findings are clearly different to typical findings in both γ3HCD and Myeloma. HCD has an appalling prognosis and this case is likely to have been ‘smouldering’ for 18 months, evidenced by the 2 pneumonias and persistent night sweats. There is no lymphadenopathy or organomegaly associated with γ3HCD. The immunophenotype of the malignant plasma cells is unique. Other atypical features include frank proteinuria, with a HC in the urine, but normal renal function and no radiological or biochemical evidence of bone involvement. We propose that this unique biclonal myeloma has distinct immunological and clinical features.
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Mehta, P. D., S. D. Cook, P. K. Coyle, R. A. Troiano, C. S. Constantinescu, and A. M. Rostami. "Free light chains in multiple sclerosis urine." Multiple Sclerosis Journal 4, no. 3 (June 1998): 254–56. http://dx.doi.org/10.1177/135245859800400331.
Abstract:
We measured free kappa (k) and lambda (l) light chains in urine from patients with definite multiple sclerosis (MS), other neurologic diseases (OND), and normal controls by using an enzyme linked immunosorbent assay. Both k and l light chains were higher in MS than OND or controls. In seven of eight relapsing-remitting (R-R) MS patients serial studies showed that urinary k chains were elevated during periods of worsening, and decreased during clinical recovery. In contrast, the levels of k chains did not correlate with clinical activity in 10 progressive (P) MS patients. Further correlation of urinary light chains with neurologic evaluations in R-R and P MS patients over a longer period are needed to determine their clinical and biological relevance.
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Kaplan, Batia, Esther Ganelin-Cohen, Sizilia Golderman, and Avi Livneh. "Diagnostic utility of kappa free light chains in multiple sclerosis." Expert Review of Molecular Diagnostics 19, no. 4 (February 27, 2019): 277–79. http://dx.doi.org/10.1080/14737159.2019.1586535.
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Markowitz, Glen S., Raymond S. Flis, Neeraja Kambham, and Vivette D. D'Agati. "Fanconi syndrome with free kappa light chains in the urine." American Journal of Kidney Diseases 35, no. 4 (April 2000): 777–81. http://dx.doi.org/10.1016/s0272-6386(00)70032-1.
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Yap, Clementine YF, Pey Wah Wong, and Tar Choon Aw. "Free Kappa and Lambda Light Chains in Plasma Cell Dyscrasias." Proceedings of Singapore Healthcare 20, no. 1 (March 2011): 64–66. http://dx.doi.org/10.1177/201010581102000111.
17
Singh, Gurmukh. "Concentrations of Serum Free Light Chains in Kappa and Lambda Lesions in Light-Chain Myelomas." Laboratory Medicine 50, no. 2 (November 13, 2018): 189–93. http://dx.doi.org/10.1093/labmed/lmy067.
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Augustson, Bradley M., Steven D. Reid, Graham P. Mead, Mark T. Drayson, J. Anthony Child, and Arthur R. Bradwell. "Serum Free Light Chain Levels in Asymptomatic Myeloma." Blood 104, no. 11 (November 16, 2004): 4880. http://dx.doi.org/10.1182/blood.v104.11.4880.4880.
Abstract:
Abstract Introduction: Patients with asymptomatic myeloma fulfil two of the diagnostic criteria for myeloma having more than 10% bone marrow plasma cells and an M protein of greater than 30g/l, but they are asymptomatic with no evidence of end organ or tissue damage. The median time to disease progression is 12–32 months. These patients do not require treatment but do require monitoring for progression to symptomatic myeloma. Predicting progression of asymptomatic myeloma would be of clinical benefit to optimise monitoring and initiate treatment prior to substantial end organ damage. However monoclonal spike, plasma cell labelling index, bone marrow plasmacytosis, immunoparesis and the presence of Bence Jones protein have limited value in predicting progression. Abnormal levels of serum free light chains are present in 95% of all multiple myeloma patients and have clinical benefit in diagnosis and monitoring of disease. In monoclonal gammopathy of undetermined significance (MGUS) 60% of patients have abnormal serum free light chain ratios and are an independent risk factor for progression to myeloma. The aim of this study was to examine the serum of asymptomatic patients for serum free light chains at diagnosis and to determine if they are predictive of disease progression. Methods: Archived presentation sera were studied from forty three asymptomatic myeloma patients who had been registered into United Kingdom Medical Research Council trials (1980 – 2002). Archived presentation sera were assayed for serum free light chains using the serum free light chain assay on an Olympus AU400 analyzer. Times to progression for those with abnormal versus normal serum free light chain ratios were compared. Times to progression were examined by Kaplan-Meier survival curves and log-rank sum statistical analysis. Results: Abnormal serum free light ratios were present in 36/43 (84%) of asymptomatic myeloma patients at the time of diagnosis and the remaining 7 patients had normal ratios. The median follow-up time for all 43 patients was 2807 days. Six patients with a normal kappa/lambda ratio had a median time to progression of 1323 days. In contrast, 26 patients with abnormal serum free kappa/lambda ratios had a median time to progression of 713 days. Ten patients who had an abnormal kappa/lambda ratio had not progressed at the time of follow-up. Although the median time to progression of patients with normal serum free light chain ratios was greater than those with abnormal ratios, this did not reach statistical significance (p<0.13). Conclusions: In summary, 84% of asymptomatic myeloma patients have an abnormal kappa/lambda ratio at diagnosis, in comparison with 95% of multiple myeloma and 60 % of (MGUS) patients. Furthermore, our data suggest that those with normal serum free light chain ratio may progress more slowly than those with abnormal ratios. Due to the small number of patients in this study, this did not reach statistical significance. In the spectrum of malignancy from MGUS to asymptomatic and symptomatic myeloma serum free light chain levels have an increasing frequency of abnormality and are associated with increased risk of progression to symptomatic myeloma.
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Levinson, Stanley S. "kappa/lambda index for confirming urinary free light chain in amyloidosis AL and other plasma cell dyscrasias." Clinical Chemistry 37, no. 6 (June 1, 1991): 1122–26. http://dx.doi.org/10.1093/clinchem/37.6.1122.
Abstract:
Abstract Primary systemic amyloidosis (AL), a disease involving the deposition of immunoglobulin light chains in tissue, is caused by a plasma cell dyscrasia. In the case of amyloidosis reported here, no monoclonal component was seen upon routine protein electrophoresis of serum or urine nor was a bone marrow analysis positive for AL. Immunofixation electrophoresis did not show a typical paraprotein band but did show, in the gamma region, two large diffuse bands and a lower concentration of oligoclonal-type bands, all of which stained for free lambda but not for free kappa chain. The ratio of kappa to lambda chains in urine was 0.178, much less than the ratio in serum (1.3). Six other urine samples from a group of patients with documented Bence Jones proteinuria also exhibited kappa/lambda ratios that differed manyfold from the ratios in their corresponding serum samples. On the other hand, the kappa/lambda ratios from seven controls (seven patients with generalized proteinuria unrelated to plasma cell dyscrasia) were similar in serum and urine. This difference between the kappa/lambda ratios from serum and urine can be expressed as a kappa/lambda index. The index was significantly different (P less than 0.01) between the two patient groups compared here, and was useful in confirming the presence of Bence Jones protein in this case with a difficult-to-interpret electrophoretic pattern. Although the kappa/lambda ratio has been widely used for confirmation and identification of monoclonal components in serum, its use in clinical laboratories has not been widely extended to urine. Comparison of serum and urine kappa/lambda ratios as a kappa/lambda index may help reduce the need for more complex immunoelectrophoresis techniques in identifying free light chains in urine.
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Šegulja, Dragana, Danica Matišić, Karmela Barišić, and Dunja Rogić. "Verification study of free light chains assays on reagent-optimized analysers." Biochemia medica 29, no. 3 (October 15, 2019): 579–86. http://dx.doi.org/10.11613/bm.2019.030709.
Abstract:
Introduction: Our aim was to compare analytical specifications of two assays (monoclonal vs. polyclonal) for free light chains (FLCs) quantification optimized for two different analytical platforms, nephelometer ProSpec (Siemens, Erlangen, Germany) and turbidimetric analyser Optilite (The Binding Site, Birmingham, UK). Materials and methods: The evaluation included verification of the precision, repeatability and reproducibility, estimation of accuracy and method comparison study with 37 serum samples of haematological patients. Kappa and lambda FLC were measured in each sample by both methods and kappa/lambda ratio was calculated. Results: Results show satisfactory precision of both methods with coefficients of variation for ProSpec of CVwr = 2.20% and CVbr = 3.44%, and for Optilite CVwr = 2.82% and CVbr = 4.15%. Estimated bias for FLC lambda was higher on the ProSpec analyser, but bias for FLC kappa was higher on the Optilite analyser. Correlation coefficients were 0.98; P < 0.001 for FLC kappa and 0.97; P < 0.001 for FLC lambda. Considering normal/pathological FLC ratio moderate agreement within assays was detected (κ = 0.621). When the results were categorized according to criteria for progressive disease, 4/37 (0.10) cases were differently classified. Lambda FLC values by Optilite in three samples with monoclonal FLC lambda were more than twelve times higher than by ProSpec. A 25% difference in FLC ratio was detected in 16/37 (0.43) and 50% difference in 13/37 (0.35) patients. Conclusions: All manufacturers’ precision claims could not be achieved in the verification study. The comparison of results to biological variations data showed that coefficients of variations are acceptable for both assays. The assays should not be used interchangeably in haematological patients.
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Singh, Gurmukh. "Serum and Urine Protein Electrophoresis and Serum-Free Light Chain Assays in the Diagnosis and Monitoring of Monoclonal Gammopathies." Journal of Applied Laboratory Medicine 5, no. 6 (November 1, 2020): 1358–71. http://dx.doi.org/10.1093/jalm/jfaa153.
Abstract:
Abstract Background Laboratory methods for diagnosis and monitoring of monoclonal gammopathies have evolved to include serum and urine protein electrophoresis, immunofixation electrophoresis, capillary zone electrophoresis, and immunosubtraction, serum-free light chain assay, mass spectrometry, and newly described QUIET. Content This review presents a critical appraisal of the test methods and reporting practices for the findings generated by the tests for monoclonal gammopathies. Recommendations for desirable practices to optimize test selection and provide value-added reports are presented. The shortcomings of the serum-free light chain assay are highlighted, and new assays for measuring monoclonal serum free light chains are addressed. Summary The various assays for screening, diagnosis, and monitoring of monoclonal gammopathies should be used in an algorithmic approach to avoid unnecessary testing. Reporting of the test results should be tailored to the clinical context of each individual patient to add value. Caution is urged in the interpretation of results of serum-free light chain assay, kappa/lambda ratio, and myeloma defining conditions. The distortions in serum-free light chain assay and development of oligoclonal bands in patients‘ status post hematopoietic stem cell transplants is emphasized and the need to note the location of original monoclonal Ig is stressed. The need for developing criteria that consider the differences in the biology of kappa and lambda light chain associated lesions is stressed. A new method of measuring monoclonal serum-free light chains is introduced. Reference is also made to a newly defined entity of light chain predominant intact immunoglobulin monoclonal gammopathy. The utility of urine testing in the diagnosis and monitoring of light chain only lesions is emphasized.
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Saadeh, Ruba S., Sandra C. Bryant, Andrew McKeon, Brian Weinshenker, David L. Murray, Sean J. Pittock, and Maria Alice V. Willrich. "CSF Kappa Free Light Chains: Cutoff Validation for Diagnosing Multiple Sclerosis." Mayo Clinic Proceedings 97, no. 4 (April 2022): 738–51. http://dx.doi.org/10.1016/j.mayocp.2021.09.014.
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Süße, Marie, Fritz Feistner, Matthias Grothe, Matthias Nauck, Alexander Dressel, and Malte Johannes Hannich. "Free light chains kappa can differentiate between myelitis and noninflammatory myelopathy." Neurology - Neuroimmunology Neuroinflammation 7, no. 6 (September 18, 2020): e892. http://dx.doi.org/10.1212/nxi.0000000000000892.
Abstract:
ObjectiveTo test the hypothesis that the intrathecal synthesis of free light chain kappa (FLC-k) can be used as a CSF biomarker to differentiate patients with myelitis due to multiple sclerosis (MS), myelitis due to neuromyelitis optica spectrum disease (NMOSD), and noninflammatory myelopathy, we analyzed FLC-k in 26 patients with MS myelitis, 9 patients with NMOSD myelitis, and 14 patients with myelopathy.MethodsThis is a retrospective monocentric cohort study. FLC-k were analyzed using the nephelometric Siemens FLC-k kit in paired samples of CSF and sera. Intrathecal fraction (IF) of FLC-k was plotted in a FLC-k quotient diagram.ResultsNinety-six percent of patients with MS myelitis had an intrathecal synthesis of FLC-k in comparison with 55.6% for NMOSD and 14.3% of patients with noninflammatory myelopathy. The locally synthesized absolute amount of FLC-k was significantly higher in patients with myelitis due to MS than in patients with NMOSD (p = 0.038) or noninflammatory myelopathy (p < 0.0001). The sensitivity of FLC-k synthesis to detect inflammation in patients with myelitis is 85.7%. Using a receiver operating characteristic analysis, FLC-k IF >78% can discriminate patients with myelitis due to MS and NMOSD with a sensitivity of 88.5% and a specificity of 88.9%ConclusionsWith the hyperbolic reference range in quotient diagrams for FLC-k, it is possible to distinguish inflammatory myelitis from noninflammatory myelopathies. An FLC-k IF >78% can be a hint to suspect myelitis due to MS rather than NMOSD.
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Bayart, J. L., N. Muls, and V. van Pesch. "Free Kappa light chains in neuroinflammatory disorders: Complement rather than substitute?" Acta Neurologica Scandinavica 138, no. 4 (June 13, 2018): 352–58. http://dx.doi.org/10.1111/ane.12969.
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Čabarkapa, Velibor, Zoran Stošić, Mirjana Đerić, Ljiljana Vučurević-Ristić, and Mirjana Drljača. "The Importance of Free Light Chains of Immunoglobulins Determination in Serum." Journal of Medical Biochemistry 26, no. 4 (December 1, 2007): 269–73. http://dx.doi.org/10.2478/v10011-007-0032-6.
Abstract:
The Importance of Free Light Chains of Immunoglobulins Determination in SerumFor many years, Bence Jones proteinuria has been an important diagnostic marker for multiple myeloma. Relatively new serum tests for free kappa and free lambda light chains of immunoglobulins reflect the production of free light chains more accurately than urine tests. In this study, we examined the value of serum free light chains measurement in the diagnosis of some neoplastic diseases and the discrepance between the findings of serum protein electrophoresis and serum free light chains. Thirty one patients (f=19, m=12) were included in the study, most of them with blood malignant diseases. The results show that in six patients with normal gamma and beta electrophoresis fractions there are abnormal levels of free light chains and/or an abnormal κ/LD ratio. In 20 patients we found an abnormal κ/LD ratio, and in 21 patients we found an abnormal κ or LD level, or both. The obtained results show the important role of serum free light chains determination in identifying patients with monoclonal gammopathies.
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Treger, Rebecca, Kathleen Hutchinson, Andrew Bryan, and Chihiro Morishima. "Lambda monoclonal free light chain abnormalities detected by a serum immunofixation electrophoresis assay are underrepresented by quantitative serum free light chain results." American Journal of Clinical Pathology 156, Supplement_1 (October 1, 2021): S13—S14. http://dx.doi.org/10.1093/ajcp/aqab189.023.
Abstract:
Abstract Protein and immunofixation (IFIX) electrophoresis are used to diagnose and monitor monoclonal gammopathies. While IFIX detects clonal production of intact immunoglobulins and free light chains (FLC), the latter can also be quantified using a serum free light chain (SFLC) assay, in which polyclonal antisera detects epitopes specific for free kappa (KFLC) or lambda light chains (LFLC). An abnormal KFLC: LFLC ratio (KLR) serves as a surrogate for clonality. While the SFLC assay is highly sensitive, normal LFLC (<2.63mg/dL) and KLR results (>0.26 & <1.65) were found in samples with distinct lambda monoclonal free light chains visualized by IFIX (X-LMFLC). To investigate this discordance, contemporaneous SFLC or KLR values were evaluated for their ability to accurately classify monoclonal FLCs identified by IFIX. We performed a retrospective analysis of serum and urine IFIX (Sebia Hydrasys) and SFLC (Freelite®, Binding Site) results from our institution between July 2010 through December 2020, using R 4.0.2 and Tidyverse packages. From among 9,594 encounters in which a single monoclonal component was initially identified by IFIX, 157 X-LMFLC and 131 X-KMFLC samples were analyzed. Elevated LFLC with normal KFLC was identified in 105/157 X-LMFLC samples (67%), while both LFLC and KFLC were elevated in 42/157 samples (27%). Concordance between X-KMFLC and KFLC was markedly higher, where 122/131 samples (93%) displayed elevated kappa FLC (>1.94mg/dL) with normal LFLC, and only 7/131 X-KMFLC samples (5%) possessed both elevated KFLC and LFLC. The use of KLR to identify pathogenic monoclonal free light chains improved lambda concordance to 85%; however, 19/157 (12%) of X-LMFLC samples still exhibited normal KLR. High concordance of 98% was again observed for X-KMFLC with abnormal KLR. When samples were segregated according to normal or impaired renal function (eGFR > or ≤60mL/min/1.73m², respectively), this disparate identification of X-LMFLC and X-KMFLC by the SFLC assay persisted, suggesting that renal dysfunction (as measured by eGFR) does not underlie this phenomenon. Lastly, we corroborated the above findings in a larger sample population by examining patients with urine Bence Jones FLC identified by IFIX who had free or intact monoclonal components in serum (N=724), grouped by lambda or kappa light chain involvement. The cause(s) of the discrepant performance by the Freelite® SFLC assay, relative to the Sebia Hydrasys IFIX assay, for identifying lambda FLC components is currently unclear. Possible contributory factors include assay reference range cutoffs, other patient disease parameters, and differences in assay-specific polyclonal antisera. Future analyses of these factors will help to further characterize SFLC assay performance and elucidate how interpretation of composite serum FLC test results can be improved to better guide patient management.
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Levinson, S. S., and D. F. Keren. "Free light chains of immunoglobulins: clinical laboratory analysis." Clinical Chemistry 40, no. 10 (October 1, 1994): 1869–78. http://dx.doi.org/10.1093/clinchem/40.10.1869.
Abstract:
Abstract The increased sensitivity of immunofixation electrophoresis (IFE) over prior electrophoretic methods has led to renewed interest in the study of free light chains. Here, we discuss problems associated with the identification of monoclonal free light chains (Bence Jones proteins) in urine. Besides reviewing the nature of the sample specimens and the assays themselves, we discuss the physiology, biochemistry, genetics, and immunological properties of these molecules. Direct measurement of kappa/lambda ratios may ultimately be useful, but all commercial methods available now lack sufficient sensitivity. IFE is the preferred method because of its sensitivity and ease of interpretation. There are, however, difficulties associated with the interpretation of urinary IFE patterns, because the technique does not include an intrinsic mechanism for antibody-antigen titration and because of its great sensitivity in the absence of quantification. Problems of interpretation are discussed.
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Sidana, Surbhi, Lisa Rybicki, Frederic J. Reu, and Thomas Daly. "High Serum Free Kappa Chains Are Frequently Missed By Serum Immunofixation." Blood 124, no. 21 (December 6, 2014): 5708. http://dx.doi.org/10.1182/blood.v124.21.5708.5708.
Abstract:
Abstract Background: Serum free light chains (sFLC) and immunofixation (IFE) analysis are used to detect monoclonal proteins. We noticed that some multiple myeloma (MM) patients (pts) had negative IFE results despite very high sFLC levels. This analysis was done to determine the frequency of this finding in a large cohort. Methods: Following IRB approval, samples with simultaneous sIFE and sFLCs ordered from 1/2013 to 9/2013 were identified by querying our lab electronic database. Freelite (R) Human Kappa & Lambda Free kit (The Binding Site, Birmingham, UK) was used for sFLC and SPIFE® ImmunoFix-15 gels (Helena Laboratories, Beaumont, TX) for IFE. Clinical review was performed for a subset of patients with discrepant results between the two assays. Results: 4404 samples from 2200 pts were identified with simultaneous sFLC and sIFE results. Overall 348 of 4404 (7.9%) samples had an abnormal sFLC ratio but a negative sIFE. Of 205 pts (457 samples) with involved serum free kappa above the expected IFE threshold (200 mg/L), 42 pts (103 samples) had negative sIFEs (20.5% pts; 22.5% samples) despite median free kappa of 556.6 mg/L (range 208.1 to 4954.4). This was much less common for involved free lambda. Only 4 of 107 pts with free lambda above 200mg/L had negative sIFEs (3.7%). Information of the nature of the plasma cell disorder was available on 40 of the 42 patients with free kappa > 200mg/L and negative IFE. In this group, 62.5% (n=25) had symptomatic MM, 12.5% (n=5) had asymptomatic MM, 5% (n=2) had light chain amyloidosis, 5% (n=2) had both amyloidosis and MM, and 15% (n=6) had MGUS or a not yet fully worked up plasma cell disorder. Conclusions: Serum IFE, with a commonly used kit, missed about 20% of patients with free kappa above the expected IFE threshold, while free lambda was detected more reliably. Results suggest current criteria for complete remission which rely on immunofixation and bone marrow plasma cell infiltration may need to be revised for kappa light chain myeloma. Disclosures No relevant conflicts of interest to declare.
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Einarsson Long, Thorir, Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Ingigerdur Sverrisdottir, Elias Eythorsson, Olafur Indridason, Runolfur Palsson, et al. "Revised Definition of Free Light Chains in Serum and Light Chain Monoclonal Gammopathy of Undetermined Significance: Results of the Istopmm Study." Blood 142, Supplement 1 (November 28, 2023): 535. http://dx.doi.org/10.1182/blood-2023-188547.
Abstract:
Background: Serum free light chain (FLC) measurement, consisting of serum free kappa, serum free lambda, and a calculated FLC ratio (kappa/lambda), plays a pivotal role in the diagnosis, risk stratification and management of plasma cell disorders. Light chain monoclonal gammopathy of undetermined significance (LC-MGUS), is defined as abnormal FLC ratio with elevation of the involved FLC without evidence of heavy chain M protein or end-organ damage attributed to the plasma cell disorder. Several years ago, reference intervals for serum kappa (3.3-19.4 mg/L) and lambda (5.7-26.3 mg/L) FLC and FLC ratio (0.26-1.65) were defined in a small retrospective cohort (N = 282) of healthy individuals. Limitation of these reference intervals include inaccurate distributions among individuals with impaired kidney function. Recently, we addressed this matter in a large population-based study focusing on individuals with estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m 2, the results of which led to redefined reference intervals for patients with chronic kidney disease (Long et al, Blood Cancer J. 2022). Here, using a large cohort (N=41,882) of screened individuals, we aimed to determine FLC reference intervals in individuals with normal kidney function (eGFR ≥ 60 mL/min/1.73m 2). Methods: Data were collected from the ongoing Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study, which focuses on population-based screening for MGUS. A total of 75,422 individuals aged ≥ 40 years (representing 51% of this age group in the Icelandic population) were screened for MGUS by serum protein electrophoresis, immunofixation, and serum FLC assay (Freelite®), and two-thirds of MGUS cases were randomized to active follow-up. Participants' eGFR was calculated using serum creatinine (CKD-EPI) closest to the time of screening. Participants with heavy chain M protein, known lymphoproliferative disorder, unknown eGFR or eGFR < 60 mL/min/1.73m 2, were excluded. The 0.5 and 99.5 percentiles of kappa FLC, lambda FLC, and the FLC ratio distributions were assessed for the whole group, and subgroups of age, sex, and different levels of eGFR. A nonparametric bootstrapping method was used to calculate the 95% confidence intervals. Partitioning was determined based on the proportion of subgroups (age, sex and eGFR) outside the whole group reference interval. Results: After application of the exclusion criteria, 41,882 participants were included for further analysis. The median (interquartile range, IQR) serum free kappa was 14.3 (11.6-17.8) mg/L, serum free lambda 14.2 (11.6-17.5) mg/L, and the FLC ratio was 1.02 (0.85-1.21). The median (IQR) age was 60 (52-68) years, eGFR 84 (74-94) mL/min/1.73 m 2, and 43% were male. A strong correlation was found between age and serum kappa FLC (ρ = 0.27, p < 0.001), lambda FLC (ρ = 0.14, p < 0.001), and the FLC ratio (ρ = 0.16, p < 0.001). Use of standard reference intervals yielded abnormal results for 17.5%, 3.9%, and 4.5% of serum kappa, lambda, and FLC ratio determinations, respectively, and a prevalence of LC-MGUS of 2.0% (96% kappa and 4% lambda). Based on these findings, we established new reference intervals for serum kappa and lambda FLC and FLC ratio, partitioned by age < 70 years and ≥ 70 years (Table). Utilizing the new reference intervals the crude prevalence of LC-MGUS was 0.3% (54% kappa and 46% lambda), yielding a relative decrease of 83%. Among the group of individuals diagnosed with LC-MGUS based on standard reference intervals who did not meet the diagnostic criteria using our revised reference intervals - none had progressed to a lymphoproliferative disorder after a median follow-up time of 42 months. Conclusion: Based on prospective screening of more than 40,000 individuals and after 3.5 years of follow-up, we show that standard reference intervals for serum FLC and FLC ratio appear inaccurate for persons with preserved kidney function. We propose a revision of the reference intervals for serum FLC and FLC ratio, and a new definition of LC MGUS (Figure). Implementation of new reference intervals will decrease the rate of false positive diagnosis of LC-MGUS in individuals with preserved kidney function by more than 80%. This, in turn, will reduce the unnecessary psychological and financial burden driven by clinical evaluation and lifelong monitoring of these individuals.
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Zeldenrust, Steven R., Ellen W. Blanco, and Karl A. Nath. "Amyloidogenic lambda Light Chain Renal Toxicity: Oxidative Stress Implicated." Blood 110, no. 11 (November 16, 2007): 3531. http://dx.doi.org/10.1182/blood.v110.11.3531.3531.
Abstract:
Abstract The kidney is the most common organ involved in systemic light-chain amyloidosis (AL), seen in up to 40% of patients. Renal involvement can result in proteinuria and/or renal insufficiency. The mechanism of renal injury in amyloidosis remains unclear. We present data supporting a central role for oxidative stress in amyloid-induced renal damage. Soluble free light chains(LCs) were isolated from plasma of AL and myeloma patients obtained at the time of stem cell collection. LCs were purified by liquid-phase iso-electric fractionation of pooled plasma samples from each patient. Purified LC were incubated with cultured rat renal epithelial cells, both wild-type and heme oxygenase-1 (HO-1) over-expressing, for 16 hours. Macrophage chemoattractant protein-1 (MCP-1) induction was measured in the media by ELISA. LC from myeloma patients were used as negative controls. Significant induction of MCP-1, a sensitive indicator of oxidative stress, was seen in 4/5 patients with lambda light-chain amyloidosis and 0/4 kappa light-chain amyloidosis patients. Induction of MCP-1 was seen in only 1/8 myeloma patients tested (4 lambda and 4 kappa). Induction of MCP-1 was reduced in the presence of HO-1 overexpression, implicating oxidative stress as a critical pathway of toxicity of amyloidogenic lambda light chains in this system. These results suggest that lambda and kappa light chains may cause renal injury through distinct pathways in the kidney.
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Bradwell, Arthur R., Jean Garbincius, and Earle W. Holmes. "Serum Free Kappa to Free Lambda Ratios as an Adjunct to Serum Protein Electrophoresis for the Detection of Monoclonal Proteins in the Serum." Blood 104, no. 11 (November 16, 2004): 4856. http://dx.doi.org/10.1182/blood.v104.11.4856.4856.
Abstract:
Abstract Serum free light chain measurements have been shown to be useful in the diagnosis and monitoring of patients with monoclonal gammopathies. The present study was undertaken to evaluate the effect of adding the measurement of serum free light chain kappa to lambda ratios to the serum protein electrophoresis evaluation that we typically use as an initial screen for the detection of monoclonal proteins. We retrospectively tested 347 consecutive samples from individuals who had no previous history of plasma cell dyscrasia and had not previously had a serum or urine electrophoresis or immunofixation electrophoresis test at our institution. The quantitative serum protein electrophoresis test that was ordered was performed using Hydragel Beta 1- Beta 2 gels and Hydrasis instrument (Sebia, Inc., Norcross, GA). The protein content of the electrophoresis zones were quantitated by scanning densitometry and the electrophoresis pattern of each sample was qualitatively examined for abnormal bands and suspicious findings by a single, experienced observer. Serum free light chain concentrations and the serum free light chain kappa to lambda ratios were determined using the Freelite Human Kappa and Lambda Kits (The Binding Site Ltd, Birmingham, UK) and the Immage analyzer (Beckman Coulter Inc., Brea, CA). The serum free light chain kappa to lambda ratios were outside the reference interval (0.25 to1.65) in 23 of the samples. Ten abnormal ratios were observed among a group of 57 samples that had either positive or suspicious qualitative evaluations for the presence of a restriction or that demonstrated hypo-gammaglobulinemia. Both abnormalities led to recommendations for follow-up testing, which confirmed the presence of a monoclonal protein in 21 of the samples. Six abnormal ratios were observed among a group of 159 specimens that had quantitative abnormalities in albumin or one or more of globulin fractions (hypo-gammaglobulinemia excepted) and normal qualitative evaluations. Seven abnormal ratios were observed among a group of 131 samples that had normal quantitative results and normal qualitative evaluations. Follow-up testing is not usually recommended for serum protein electrophoresis results like those in the latter two groups. We found that the addition of the serum free light chain kappa to lambda ratio to the serum protein electrophoresis test increased the number of abnormal screens that would have required further clinical and/or laboratory evaluation by 23%(i.e. from 57 to 70). Given the high specificity of the serum free light chain kappa to lambda ratio for monoclonal light chains, the additional 13 abnormal samples identified by this test are expected to have a high likelihood of harboring a monoclonal protein that would have otherwise eluded detection. Pending a definitive prospective study, we estimate that the addition of a serum free light chain kappa to lambda ratio to the serum protein electrophoresis screen would increase the rate of detection of serum monoclonal proteins by as much as 1.6-fold.
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Moesbauer, Ulrike, Heike Schieder, Helmut Renges, Francis Ayuk, Axel Zander, and Nicolaus Kröger. "Serum Free Light Chain [FLC] Assay in Multiple Myeloma Patients Who Achieved Negative Immunofixation after Allogeneic Stem Cell Transplantation." Blood 106, no. 11 (November 16, 2005): 2023. http://dx.doi.org/10.1182/blood.v106.11.2023.2023.
Abstract:
Abstract The quantitative assay for free light chains [FLC] has been reported to be sensitive and specific for detecting and monitoring free light chain diseases such as multiple myeloma. To evaluate the sensitivity of FLC for monitoring patients in complete remission for early detection of relapse, the measurement of more than 250 serum free light chains were performed with the commercial available Freelite TM kit [Binding Site] in 26 patients who achieved complete remission with negative immunofixation after dose reduced allogeneic stem cell transplantation. The patient groups were divided in those who remained immunofixation negative [n=12, group 1] during follow-up of at least 1 year and those who had been immunofixation negative but became positive during follow-up [n=9, group 2] and those who had achieved near complete remission with positive immunofixation but then became immunofixation negative during follow-up [n=5, group 3]. In group 1 the measuring of 105 FLC concentration and kappa/lambda ratio was performed in 12 patients. In 10 patients [83 %] free light concentration of kappa or lambda remained within the normal range during follow-up of more than 1 year. In 2 patients [17 %] kappa or lambda FLC concentration was above the normal range, but remained stable without any signs of increasing amount. Group 2 consisted of 9 patients who had been immunofixation negative but became positive during follow-up. In all patients an increase of the corresponding free light chain could be observed in serum. In 4 patients a very close monitoring of immunofixation and free light assay was performed and an at least 25 % increase of the free light concentration in serum was observed at a median of 97 days before immunfixation became positive. In group 3 five patients who had been immunofixation positive became negative during follow-up. In all of the patients the free light concentration was within the range at time of negative immunofixation. The corresponding free light concentration dropped down and reached normal level at a median of 38 days before the patients had achieved negativity of immunofixation. These results suggest that serum free light chain assay allows monitoring of patients with complete remission and might detect early relapse before immunofixation becomes positive. Thus, an early increase of free light chain assay in immunofixation negative patients after allogeneic transplantation might be an useful guide for adoptive immunotherapy strategies to prevent clinical relapse.
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Long, Thorir E., Olafur S. Indridason, Runolfur Palsson, Stephen Harding, Ola Landgren, and Sigurdur Y. Kristinsson. "The Effect of Kidney Function on Reference Intervals of Serum-Free Light Chains and Free Light Chain Kappa/Lambda Ratio." Journal of the American Society of Nephrology 32, no. 10S (October 2021): 743. http://dx.doi.org/10.1681/asn.20213210s1743b.
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Rudick, RA, SV Medendorp, M. Namey, S. Boyle, and J. Fischer. "Multiple sclerosis progression in a natural history study: Predictive value of cerebrospinal fluid free kappa light chains." Multiple Sclerosis Journal 1, no. 3 (November 1995): 150–55. http://dx.doi.org/10.1177/135245859500100303.
Abstract:
Objectives: To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures. Background: CSF immune abnormalities are common in MS but have not been linked to disease progression. Design Methods: Thirty-six patients with definite (n=28), probable (n=2), or possible (n=6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length offollow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models. Results: By 36 months, 33% (95% Cl-10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% Cl=27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p=0.04) and 9HT (Hazard Ratio 10.77, p=0.04). Conclusions: In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.
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Hess, P. P., W. Mastropaolo, G. D. Thompson, and S. S. Levinson. "Interference of polyclonal free light chains with identification of Bence Jones proteins." Clinical Chemistry 39, no. 8 (August 1, 1993): 1734–38. http://dx.doi.org/10.1093/clinchem/39.8.1734.
Abstract:
Abstract We present a case in which kappa free light chains caused difficulty in interpreting classical urinary immunoelectrophoresis, but immunofixation electrophoresis (IFE) demonstrated the presence of a lambda-Bence Jones protein. Analysis of the urine by Ouchterlony double diffusion and IFE after gel-filtration chromatography showed that the difficulty was caused by the presence of large amounts of polyclonal free light chains. The workup also demonstrated that although IFE is the more sensitive and specific technique, IFE performed on concentrated urinary samples is especially subject to misinterpretation unless densely staining patterns are diluted and reassayed. This process of sample dilution provides a means for titrating antigen and antibody concentrations such that condition-specific patterns become visible on the gel. This workup also shows that, at some dilutions, polyclonal free light chains may migrate in the same manner as an oligoclonal band in a so-called ladder configuration. These bands were observed from both monomeric and dimeric fractions isolated by gel chromatography, consistent with reports that this pattern is largely linked to the isoelectric points of the molecules. We speculate that, in rare instances, the distinction between polyclonal and monoclonal kappa free light chains migrating as a ladder-banding pattern may be equivocal.
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Ganta, Nagapratap, Varsha Gupta, Fnu Anamika, Akshit Chitkara, Sheilabi Seeburun, and Ruchi Bhatt. "Lymphoplasmacytic Lymphoma: An Atypical Presentation with IgG Monoclonal Gammopathy." Blood 142, Supplement 1 (November 28, 2023): 4425. http://dx.doi.org/10.1182/blood-2023-191167.
Abstract:
Introduction Lymphocytic lymphoma (LPL) is a rare type of low-grade mature B-cell non-Hodgkin lymphoma, characterized by a monoclonal population of B lymphocytes, lymphoplasmacytic cells, and plasma cells. In around 95% of LPL cases, the serum immunoglobulin M (IgM) paraprotein is increased, which is correlated to Waldenstrom's Macroglobulinemia (WM), a clinicopathological disease. Only around 5% of LPL cases are associated with the serum paraproteins immunoglobulin G (IgG) or immunoglobulin A (IgA), or light chains alone, or are not linked to a paraprotein. Non-IgM LPLs have a wide range of clinical and pathological features, and MYD88 L265P mutations can occur, though at a lower frequency than WM. Hence, MYD88 testing is advised for prospective therapeutic purposes. Case Presentation A 69-year-old male was referred to a hematologist for uncontrolled epistaxis and periorbital edema. On initial workup, he had high total protein, elevated globulin, hypoalbuminemia, anemia, and proteinuria. Further investigation revealed a high IgG level with low IgM, IgA, and complement levels. Serum Protein Electrophoresis (SPEP): Increased total protein, decreased alpha two and beta globulins with a large monoclonal protein peak migrating in the gamma region, which accounts for 4.77 g/dl of the total 5.38g/dl gamma. Elevated Kappa Quantitative Free Light Chains of 355.39 (3.30 - 19.40mg/L), Decreased Lambda Quantitative Free Light Chains of 1.51 (5.71 - 26.30mg/L), Elevated Kappa Lambda Free Light Chains Ratio of 235.36 (0.26 - 1.65). Serum ImmunoFixation Electrophoresis demonstrated IgG-type kappa monoclonal protein with an additional faint band in IgG kappa. X-Ray skeletal survey showed a possible small lytic area in the inferior aspect of the C2 vertebral body, prompting him to have a cervical spine MRI which revealed no lytic lesions but an 18 mm vertebral body hemangioma inside T2. Molecular testing was positive for MYD88 Mutation c.794T>C (p. L265P) and negative for CXCR4 mutation. Plasma cell myeloma prognostic panel and chromosome analysis were normal. Flow cytometry of bone marrow aspirate showed a kappa light chain restricted plasma cell population (1.6% of total cells) with the following immunophenotype: positive for CD138, CD38, CD45, and negative for CD19, CD20, CD56, CD 117, and lambda light chains. The B-cell population showed kappa light chain restriction with the following immunophenotype: positive for CD19, CD20, and kappa light chains and negative for CD5, CD10, CD11c, CD23, and lambda light chains (Image 2). PET-CT of the whole body was negative for the extension of the disease. Transfusion with the two least incompatible PRBCs had little effect. However, plasmapheresis significantly improved his hemoglobin level by less than 7g/dl. A bone marrow biopsy revealed he had LPL with IgG Monoclonal Gammopathy (Image 1). He received one cycle of CyBorD (Cyclophosphamide, Bortezomib, Dexamethasone), followed by seven cycles of KCD (Carfilzomib, Cyclophosphamide, Dexamethasone) and Rituximab. The patient was diagnosed with low-grade B cell lymphoma with plasmocytic differentiation/lymphoplasmacytic lymphoma, with MYD88 mutation c.794T>C (p. L265P) positivity and CXCR4 mutation negativity. After plasmapheresis, the IgG level dropped to 1958. Follow-up SPEP revealed decreased alpha2 and beta globulins, decreased free lambda light chains, and increased K/L ratio. The patient was treated with Acalabrutinib, and his anemia, epistaxis, and coagulopathy resolved. Repeat PET-CT scan revealed no evidence of illness progression. Discussion LPL is not always linked with IgM monoclonal gammopathy; it can also be associated with IgG or IgA monoclonal gammopathy, light chains alone, or no monoclonal paraprotein. Non-IgM LPL has a high prevalence of extramedullary involvement, a lower rate of MYD88 mutation, and few hyper viscosity symptoms. The MYD88 mutation does not allow WM and Non-IgM LPL to be distinguished from other lymphoproliferative disorders with similar clinical and immunophenotypic features. The case described is unique as the patient has high levels of IgG (11,200) at presentation. In contrast to our patient, who has LPL with IgG Monoclonal gammopathy, approximately 95 percent of LPL patients have IgM Monoclonal gammopathy, which corresponds with WM. As a result, clinicians should be on the lookout for LPL that lacks an IgM Monoclonal Paraprotein.
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Nakaki, T., R. J. Deans, and A. S. Lee. "Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1)." Molecular and Cellular Biology 9, no. 5 (May 1989): 2233–38. http://dx.doi.org/10.1128/mcb.9.5.2233-2238.1989.
Abstract:
The 78,000-dalton glucose-regulated protein (GRP78) is a stress-inducible protein localized in the endoplasmic reticulum. It has been identified as the immunoglobulin heavy-chain-binding protein. We report here a high level of GRP78 expression in a B-cell myeloma line, NS-1, which produces only kappa light-chain proteins but is unable to secrete them. GRP78 transcription was enhanced in NS-1 cells, resulting in higher levels of GRP78 mRNA and protein than in non-immunoglobulin-producing cells. Furthermore, the nonsecreted light chains in NS-1 cells were found in specific association with GRP78. We hypothesize that in nonsecreting lymphoid cells, the presence of free, unassembled light chains in the endoplasmic reticulum could result in increased transcription of the GRP78 gene and that GRP78 can also bind to immunoglobulin light chains.
38
Nakaki, T., R. J. Deans, and A. S. Lee. "Enhanced transcription of the 78,000-dalton glucose-regulated protein (GRP78) gene and association of GRP78 with immunoglobulin light chains in a nonsecreting B-cell myeloma line (NS-1)." Molecular and Cellular Biology 9, no. 5 (May 1989): 2233–38. http://dx.doi.org/10.1128/mcb.9.5.2233.
Abstract:
The 78,000-dalton glucose-regulated protein (GRP78) is a stress-inducible protein localized in the endoplasmic reticulum. It has been identified as the immunoglobulin heavy-chain-binding protein. We report here a high level of GRP78 expression in a B-cell myeloma line, NS-1, which produces only kappa light-chain proteins but is unable to secrete them. GRP78 transcription was enhanced in NS-1 cells, resulting in higher levels of GRP78 mRNA and protein than in non-immunoglobulin-producing cells. Furthermore, the nonsecreted light chains in NS-1 cells were found in specific association with GRP78. We hypothesize that in nonsecreting lymphoid cells, the presence of free, unassembled light chains in the endoplasmic reticulum could result in increased transcription of the GRP78 gene and that GRP78 can also bind to immunoglobulin light chains.
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Berek, Klaus, Gabriel Bsteh, Michael Auer, Franziska Di Pauli, Astrid Grams, Dejan Milosavljevic, Paulina Poskaite, et al. "Kappa-Free Light Chains in CSF Predict Early Multiple Sclerosis Disease Activity." Neurology - Neuroimmunology Neuroinflammation 8, no. 4 (May 28, 2021): e1005. http://dx.doi.org/10.1212/nxi.0000000000001005.
Abstract:
ObjectiveTo investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.MethodsPatients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.ResultsA total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.ConclusionHigh κ-FLC index predicts early MS disease activity.Classification of EvidenceThis study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.
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Presslauer, Stefan, Dejan Milosavljevic, Wolfgang Huebl, Silvia Parigger, Gabriele Schneider-Koch, and Thomas Bruecke. "Kappa Free Light Chains: Diagnostic and Prognostic Relevance in MS and CIS." PLoS ONE 9, no. 2 (February 25, 2014): e89945. http://dx.doi.org/10.1371/journal.pone.0089945.
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Vecchio, D., I. Crespi, E. Virgilio, P. Naldi, M. P. Campisi, R. Serino, U. Dianzani, G. Bellomo, R. Cantello, and C. Comi. "Kappa free light chains could predict early disease course in multiple sclerosis." Multiple Sclerosis and Related Disorders 30 (May 2019): 81–84. http://dx.doi.org/10.1016/j.msard.2019.02.001.
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Fong, S., P. P. Chen, T. A. Gilbertson, R. I. Fox, J. H. Vaughan, and D. A. Carson. "Structural similarities in the kappa light chains of human rheumatoid factor paraproteins and serum immunoglobulins bearing a cross-reactive idiotype." Journal of Immunology 135, no. 3 (September 1, 1985): 1955–60. http://dx.doi.org/10.4049/jimmunol.135.3.1955.
Abstract:
Abstract The monoclonal antibody (MoAb) 17.109 recognizes a cross-reactive idiotype (CRI) associated with the light chains of Waldenstrom's macroglobulins with rheumatoid factor (RF) activity. The MoAb also reacts with a proportion of IgM-RF molecules from the sera of rheumatoid arthritis and primary Sjogren's syndrome patients, and from the sera of seropositive normal human subjects. In the present experiments, we used affinity chromatography to purify the 17.109 CRI-positive immunoglobulin from serum and have analyzed the isolated material by Western blotting. The purified 17.109 CRI-positive material from the sera of rheumatoid arthritis patients, Sjogren's syndrome patients, and normal subjects contained exclusively kappa light chains, and had demonstrated RF activity. In every case the 17.109 CRI-positive isolates reacted with antibodies against synthetic peptides corresponding to both the conserved second and third complementarity-determining regions (CDR) of the monoclonal kappa IgM-RF paraprotein Sie. The binding was inhibited specifically by the free peptides in solution. The antipeptide antibodies did not react appreciably with unfractionated human immunoglobulin. The data establish that the 17.109 CRI-positive immunoglobulin from diverse human sera have similar or identical second and third light chain CDR. These results suggest i) that the MoAb 17.109 identifies the protein product of a single or a very few V kappa genes, ii) that the ability to make kappa light chains with the 17.109-associated variable region is widespread in the human population, and iii) that the 17.109-defined kappa variable region segment is associated with IgM-RF autoantibodies.
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Sarris, Katerina, Dimitrios Maltezas, Efstathios Koulieris, Vassiliki Bartzis, Tatiana Tzenou, Sotirios Sachanas, Eftychia Nikolaou, et al. "Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia." Advances in Hematology 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/359071.
Abstract:
Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients.Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients’ series.Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients’ followup was 32 months (range 4–228).Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P=0.0005andP=0.000003, resp.) and overall survival (P=0.05andP=0.003, resp.). They also correlated withβ2-microglobulin (P=0.009andP=0.03, resp.), serum albumin (P=0.009for summated sFLC), hemoglobin (P<0.001), abnormal LDH (P=0.037andP=0.001, resp.), Binet stage (P<0.05) and with the presence of beta symptoms (P=0.004for summated sFLC).Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.
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Shammo, Jamile M., Agne Paner, MV Ramana Reddy, Rachel L. Mitchell, and Parameswaran Venugopal. "A Striking Reduction of Monoclonal Protein in a Patient with Concurrent Plasma Cell Dyscrasia and CMML-2, after Treatment with Rigosertib (01910.Na)." Blood 126, no. 23 (December 3, 2015): 5362. http://dx.doi.org/10.1182/blood.v126.23.5362.5362.
Abstract:
Abstract Rigosertib (ON 01910.Na) is a member of a broader class of unsaturated sulfone kinase inhibitors capable of inducing profound mitotic spindle abnormalities, abnormal centrosome localization, G2-M cell cycle phase arrest and mitotic catastrophe, culminating in apoptosis. Rigosertib is a Ras mimetic that interferes with phosphoinositide 3-kinase (PI-3K)/Akt, reactive oxygen species and Ras/Raf/polo-like kinase (PLK) signaling pathways. Although broadly cytotoxic against malignant cells, it is remarkably non-toxic for non-neoplastic cells. For this reason, this is a particularly attractive compound to test against neoplastic diseases of the bone marrow such as MDS and acute leukemia. This is a report of an unexpected reduction in monoclonal IgG, during a subject participation in a Phase III, randomized study of rigosertib, in patients with MDS who have either failed to respond, or progressed after receiving hypomethylating agents (ONTIME Trial). A 75-year-old man with CMML-2 had a CBC on day 1 of the trial that demonstrated leukocytosis, with absolute monocytosis, 7% blasts in the peripheral blood, Hgb of 9.4 gm/dl, and platelets of 7 K. He was transfusion dependent for both pRBCs and platelets. His chemistry panel demonstrated a high total protein of 9.9 (NL: 6.0 - 8.2 G/DL) with low albumin at 2.4 (NL: 3.5 - 5.0 G/DL); therefore, an SPEP/IPEP was performed, reporting the presence of monoclonal IgG kappa. Quantitative immunoglobulins showed an elevated IgG of 3594 mg/dl (NL: 596 - 1584 MG/DL). Serum free light chains were remarkable for an elevated Kappa fraction at 38.94 (NL: 0.33 - 1.94 MG/DL). On day 1 of cycle 5 of rigosertib, he was started on pulse decadron for 2 months, after which his disease progressed to AML, and he died shortly thereafter. Neither his bone marrow biopsies, nor his hematological parameters demonstrated a response to treatment with rigosertib. In contrast and interestingly, his total protein, serum kappa light chain load, and total IgG, all were drastically reduced shortly after initiation of rigosertib, as can be seen in the graph below depicting a substantial drop in his kappa light chain as well as the kappa/light chain ratio. Importantly, reduction in the monoclonal protein was noted prior to initiation of pulse decadron. Even though his initial bone marrow biopsy did not note a monoclonal plasma cell population, a subsequent bone marrow reported a low-level involvement with a plasma cell dyscrasia, with kappa light chain restriction. His final bone marrow biopsy confirmed progression to AML, but the previously seen plasma cell dyscrasia was no longer present. Conclusion: We are not aware of prior reports describing a similar effect of rigosertib on M-proteins. However, in vitro studies with rigosertib have demonstrated antitumor effects and induction of apoptosis in myeloma cell lines1. This observation merits further exploration of this agent in multiple myeloma. References: 1. Reddy MV, et al. Discovery of a Clinical Stage Multi-Kinase Inhibitor Sodium (E)-2-{2-Methoxy-5-[(2',4',6'-trimethoxystyrylsulfonyl)methyl]phenylamino}acetate (ON01910.Na): Synthesis, Structure-Activity Relationship, and Biological Activity. J Med Chem, 2011, 54(18):6254-76. Figure 1. Decrease in serum free kappa light chains following initiation of rigosertib. Figure 1. Decrease in serum free kappa light chains following initiation of rigosertib. Figure 2. Decrease in kappa/lambda ratio following initiation of rigosertib. Figure 2. Decrease in kappa/lambda ratio following initiation of rigosertib. Disclosures Shammo: Onconova: Research Funding.
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Lee, Won Sok, and Gurmukh Singh. "Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies." Journal of Clinical Medicine Research 10, no. 7 (2018): 562–69. http://dx.doi.org/10.14740/jocmr3383w.
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Giussani, Marta, Chiara Maura Ciniselli, Alessandra Macciotta, Rossella Panella, Paolo Verderio, Chiara Bonini, and Daniele Morelli. "κ and λ urine free light chains: a new method for quantification." Tumori Journal 106, no. 6 (January 20, 2020): 457–63. http://dx.doi.org/10.1177/0300891619898533.
Abstract:
Background: Immunofixation electrophoresis of urinary proteins, coupled with densitometric analysis, is the gold standard method for determining urinary monoclonal free light chains (FLCs), i.e. Bence Jones protein. Recently, immunochemical methods have been developed for Bence Jones protein quantification, but no such method has been widely adopted. This study evaluated a new antibody-based immunoturbidimetry method for urinary FLC quantification, using immunofixation electrophoresis as reference. Methods: κ and λ FLCs were measured in urine specimens from 95 (training cohort) and 103 (testing cohort) patients by both immunofixation electrophoresis and immunoturbidimetry. Results: There was almost perfect concordance in the training cohort between the new immunoturbidimetry assay and immunofixation electrophoresis and substantial agreement, with Cohen kappa of 0.85 and 0.75, for κ and λ FLC determination, respectively. Results were confirmed in the testing cohort, where Cohen kappa was 0.86 for κ and 0.94 for λ FLCs. The κ FLC assay had 88% sensitivity and 98%–100% specificity; the λ FLC assay had 94% and 96% sensitivity and 91% and 99% specificity in the training and testing cohorts, respectively. Conclusions: The new immunochemical method has a satisfactory performance and almost perfect agreement with immunofixation electrophoresis and gives the advantage of FLC quantification.
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Lee, Won, and Gurmukh Singh. "Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Underproduction and Underdetection of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies." American Journal of Clinical Pathology 150, suppl_1 (September 21, 2018): S145—S146. http://dx.doi.org/10.1093/ajcp/aqy112.346.
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Vavrova, Jaroslava, Bedrich Friedecky, Milos Tichy, Magdalena Holeckova, Vladimir Maisnar, and Roman Hajek. "The Evaluation of Light Chains USING ELISA Method." Blood 112, no. 11 (November 16, 2008): 5147. http://dx.doi.org/10.1182/blood.v112.11.5147.5147.
Abstract:
Abstract Introduction: Free light chain assay (FLC) has moved into clinical practice based on the building evidence of its utility in multiple myeloma (MM) and other monoclonal gammopathies. The purpose of the study is to verify the effectiveness of the basic parameters relevant to serum free light chain analysis using ELISA method and to compare it with the well-established FreeLite assay. Methodology and sample collection: ELISA method was tested using diagnostic kit developed by Biovendor (Czech Republic). Immunoturbidimetric measurement using the FreeLite kit (The Binding Site), adapted on the Modular P (Roche), and was used as a reference method. Regression analysis, developed by Passing and Bablok, expressed by equation Y = −9,84 + 1,53 X allowed to compare the two methods. In total, the results of serum FLC determination in 40 donors and in 202 patients with monoclonal gammopathies were compared. Results: Reference intervals were tentatively determined based on an analysis of male and female blood donor samples. The ratio kappa/lambda was from 0.24 to 1.17 by use of ELISA method and from 0.53 to 1.92 by reference immunoturbidimetric method. Intermediate measurement precision was obtained as follows: (intermediate) kappa using ELISA 6,6–11,0 %, using immunoturbidimetric method 5,6–6,9 %; lambda using ELISA 7,3–8,6 %, using immunoturbidimetric method 6,1–9,2 %. Regression coefficient was R = 0, 73. We were observing the influence of sample dilution on the results and we confirmed the necessity to verify the degree of dilution in each pathologically changed sample. The main factors of a successful free light chain determination are: validity of the reference intervals, difference in diagnostic classification when using different methods. Considering the necessary dilution, every patient sample requires a special and individual attention. In many patients, an applicable result can be obtained only having repeated the measurements at different dilution levels; therefore, it is not possible to predict the number of examinations one kit can serve to. Conclusion: The determination of serum free light chains cannot be considered as a routine procedure for the time being. This analysis requires careful sample preparation and high professional level of laboratory personal. Both methods used to determine serum FLC are suitable for laboratory practice; the comparability of their predictive value in clinical practice requires a further testing.
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Чурко, А. А., and А. Ш. Румянцев. "Free Light Chains of Immunoglobulins as a Biomarker of Glomerulopathies." Juvenis Scientia, no. 3 (June 30, 2023): 42–50. http://dx.doi.org/10.32415/jscientia_2023_9_3_42-50.
Abstract:
Введение. Повышение уровня легких цепи иммуноглобулинов в сыворотке крови может рассматриваться в качестве биомаркеров активности основного заболевания и возможной мишени для новых методов лечения. Целью нашего исследования было определение уровня пСЛЦ при различных пролиферативных и непролиферативных гломерулопатиях Пациенты и методы. Обследованы 97 пациентов с хронической болезнью почек, среди них 51 мужчина и 46 женщин, средний возраст 47,5±14,6 лет. У всех обследуемых диагноз гломерулопатии был подтвержден морфологически. Уровень пСЛЦ сыворотки крови определяли методом «Freelite» («Binding Site Ltd», Великобритания). Результаты. Пролиферативные гломерулопатии были выявлены у 46 пациентов, непролиферативные — у 51. Уровень СЛЦ-каппа в сыворотке крови составил в первой группе 38,8 (18,7–61,0) мг/л, во второй — 21,7 (13,6–33,1) мг/л, р=0,003. Уровень СЛЦ-лямбда в сыворотке крови составил в первой группе 34,68 (23,1–56,4) мг/л, во второй — 25,4 (19,5–31,9) мг/л, р=0,005. В целом референсные значения для СЛЦ-каппа и СЛЦ-лямбда были превышены соответственно у 65% и 54% пациентов. Независимо от формы гломерулопатии статистически значимых взаимосвязей между пСЛЦ и традиционными показателями системного воспаления (СОЭ, С-реактивный белок) и долей полностью склерозированных клубочков выявлено не было. Заключение. Уровень пСЛЦ в сыворотке крови в основном отражает активность локального тканевого иммунного воспаления, которое поддерживается активацией В-лимфоцитов. Introduction. Light chains of immunoglobulins are not only structural elements of immunoglobulins of all classes, but can become independent units of immuno-mediated inflammatory reactions. Serum polyclonal free light chains (pFLC) are also found in a certain amount in practically healthy people. It has been shown that an increase in their serum levels can be considered as biomarkers of the activity of the underlying disease and a possible target for new treatment methods. There has been no extensive study of the role of pFLC in the pathogenesis of diseases unrelated to plasma cell diseases. The aim of our study was to determine the level of pFLC in various proliferative and non-proliferative glomerulopathies. Patients and methods. 97 patients with chronic kidney disease (CKD) were examined, among them 51 men and 46 women, average age 47.5±14.6 years. The diagnosis of glomerulopathy was confirmed morphologically in all the subjects. The serum level of pFLC was determined by the “Freelite” method (“Binding Site Ltd”, UK). The glomerular filtration rate (eGFR) was calculated using the “2021 CKD-EPI Creatinine” formula. Results. Proliferative glomerulopathies were detected in 46 patients, non-proliferative — in 51. The level of pFLC-kappa in the blood serum in the first group was 38.8 (18.7–61.0) mg/l, in the second — 21.7 (13.6–33.1) mg/l, p=0.003. The level of pFLC-lambda in the blood serum in the first group was 34.68 (23.1–56.4) mg/l, in the second — 25.4 (19.5–31.9) mg/l, p=0.005. In general, the reference values for pFLC-kappa (19.4 mg/L) and pFLC-lambda (26.3 mg/L) were exceeded in 65% (n=63) and 54% (n=52) patients, respectively. Regardless of the form of glomerulopathy, the presence of significant relationships between pFLC and the detection of signs of systemic inflammation (ESR, C-reactive protein) was not revealed. Also, no statistically significant relationship was found between serum pFLC and the proportion of completely sclerotic glomeruli. For eGFR, the statistical relationship became significant only when the eGFR was less than 60 ml/min/1.73 m2. Conclusion. The level of pFLC in the blood serum mainly reflects the activity of local tissue immune inflammation, which is supported by the activation of B-lymphocytes. In CKD C3 and more severe stages, eGFR should be taken into account when assessing the significance of an increase in serum levels of pFLC-kappa and lambda.
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Duell, Frida, Björn Evertsson, Faiez Al Nimer, Åsa Sandin, Daniel Olsson, Tomas Olsson, Mohsen Khademi, Max Albert Hietala, Fredrik Piehl, and Magnus Hansson. "Diagnostic accuracy of intrathecal kappa free light chains compared with OCBs in MS." Neurology - Neuroimmunology Neuroinflammation 7, no. 4 (June 11, 2020): e775. http://dx.doi.org/10.1212/nxi.0000000000000775.
Abstract:
ObjectiveTo determine what kappa free light chain (KFLC) metric has the highest capacity to separate healthy patients from patients with MS, we evaluated the sensitivity, specificity, and the overall diagnostic accuracy of 4 different KFLC metrics. To assess the usefulness of KFLC in the diagnostics of MS, we compared the different KFLC metrics with oligoclonal bands (OCBs), the current gold standard biochemical method to demonstrate intrathecal antibody production.MethodsCSF and plasma were collected from patients with confirmed or suspected MS, other neurological diseases, as well as symptomatic and healthy controls between May 2017 and May 2018 (n = 335) at the Department of Neurology, Karolinska University Hospital, as part of routine diagnostic workup. KFLC analysis and isoelectric focusing for the detection of oligoclonal bands (OCB) were determined and correlated with diagnosis. Receiver operating characteristic (ROC) curve analysis was used to determine accuracy.ResultsOCBs yielded a sensitivity of 87% and a specificity of 100%. All KFLC metrics showed a high sensitivity (89%–95%) and specificity (95%–100%). Using the optimal cutoff according to the Youden Index resulted for the KFLC intrathecal fraction in a cutoff of −0.41 with a sensitivity of 95% and a specificity of 97% and for CSF KFLC/CSF albumin with a cutoff of 1.93 × 10−3 with a sensitivity of 94% and specificity of 100%.ConclusionAll evaluated KFLC metrics have excellent accuracy, and both KFLC intrathecal fraction and CSF KFLC/CSF albumin are at least as good as OCB in separating patients with MS from a control group.Classification of evidenceThis study provides Class III evidence that CSF KFLC accurately distinguishes patients with MS from healthy controls.