Bibliografías temáticas / Kappa free light chains

Literatura académica sobre el tema "Kappa free light chains"

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Artículos de revistas sobre el tema "Kappa free light chains":

1

Schwenkenbecher, Philipp, Franz Konen, Ulrich Wurster, Konstantin Jendretzky, Stefan Gingele, Kurt-Wolfram Sühs, Refik Pul, Torsten Witte, Martin Stangel y 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, n.º 12 (29 de noviembre de 2018): 3796. http://dx.doi.org/10.3390/ijms19123796.

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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 y Y. Argon. "Ig light chains are secreted predominantly as monomers." Journal of Immunology 157, n.º 7 (1 de octubre de 1996): 2969–75. http://dx.doi.org/10.4049/jimmunol.157.7.2969.

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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 y R. W. Finberg. "Human B cells secrete predominantly lambda L chains in the absence of H chain expression." Journal of Immunology 146, n.º 2 (15 de enero de 1991): 599–602. http://dx.doi.org/10.4049/jimmunol.146.2.599.

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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 y Guy Pratt. "Multiple Myeloma with Monoclonal Free IgG3 Heavy Chains and Free Kappa Light Chains". Acta Haematologica 123, n.º 3 (2010): 158–61. http://dx.doi.org/10.1159/000292899.

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5

Arneth, Borros y Jörg Kraus. "The Use of Kappa Free Light Chains to Diagnose Multiple Sclerosis". Medicina 58, n.º 11 (24 de octubre de 2022): 1512. http://dx.doi.org/10.3390/medicina58111512.

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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).
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Ramsden, DB. "Multiple sclerosis: assay of free immunoglobulin light chains". Annals of Clinical Biochemistry: International Journal of Laboratory Medicine 54, n.º 1 (28 de septiembre de 2016): 5–13. http://dx.doi.org/10.1177/0004563216652175.

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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.
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Vinayek, Namita, Goetz H. Kloecker y Beth C. Riley. "Multiple Myeloma with Secretory and Non-Secretory Biclonal Gammopathy". Blood 118, n.º 21 (18 de noviembre de 2011): 5092. http://dx.doi.org/10.1182/blood.v118.21.5092.5092.

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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.
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Abbi, Kamal Kant Singh, Guido J. Tricot, Margarida Silverman, Kalyan Nadiminti y Matthew Krasowski. "Potential Pitfalls of Serum Free Light Chain Analysis to Assess Treatment Response for Multiple Myeloma". Blood 126, n.º 23 (3 de diciembre de 2015): 5308. http://dx.doi.org/10.1182/blood.v126.23.5308.5308.

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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.
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Rudick, Richard A., Adam Pallant, Jean M. Bidlack y Robert M. Herndon. "Free kappa light chains in multiple sclerosis spinal fluid". Annals of Neurology 20, n.º 1 (julio de 1986): 63–69. http://dx.doi.org/10.1002/ana.410200111.

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Pratt, G., A. Richter, A. Huisoon, M. Drayson y S. Harding. "A177 Multiple Myeloma with Monoclonal Free IgG3 Heavy Chains and Free Kappa Light Chains". Clinical Lymphoma and Myeloma 9 (febrero de 2009): S30—S31. http://dx.doi.org/10.1016/s1557-9190(11)70494-2.

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Artículos de revistas

Tesis sobre el tema "Kappa free light chains":

1

Vecchio, Domizia. "Kappa free light chains as a biomarker in multiple sclerosis". Doctoral thesis, Università del Piemonte Orientale, 2021. http://hdl.handle.net/11579/128428.

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Introduction. Mulple Sclerosis (MS) cerebrospinal fluid (CSF) hallmarks are increased intrathecal immunoglobulins (Ig) and free light chains of kappa subtype (KFLC). Aims . To evaluate KFLC towards MS diagnosis and prognosis. Methods. We enrolled subjects who underwent CSF study in their diagnosc work up at the Novara University Hospital. KFLC were measured in CSF and serum by nephelometry to calculate kappa index:(CSF KFLC/serum KFLC)/(CSF albumin/serum albumin). Results. First, CSF KFLC were significantly higher in MS versus not-MS, and we defined a cut-off of 5 for kappa index in a ROC analysis. Moreover, oligoclonal bands (OB: gold-standard method to detect intrathecal synthesis) and kappa index had similar accuracy in diagnosing MS. We introduced in clinical pracce the sequenal use of kappa index (first test) and OB (confirmave procedure) as quick, accurate, less expensive and not-related operators’ interpretaon. Secondly, we compared the efficiency of KFLC to IgG (or Link) index (as the rao of CSF/serum IgG and albumin, historically used as quantave marker of MS intrathecal synthesis), and using KFLC through different interpretaon approaches. Despite OB were confirmed to be a gold-standard, the KFLC, calculated as kappa index, confirmed their accuracy in MS diagnosis. Thirdly, concerning the prognosc value of intrathecal synthesis, we evaluated the role of KFLC in predicng MS early progression. Kappa index resulted in a significant predictor for disability being higher in paents who developed greater MS severity score (a measure of disability over me) at last follow up. We then evaluate the prognosc value of KFLC in radiologically and clinically isolated syndromes (RIS-CIS). RIS-CIS paents who converted to MS showed greater kappa index and CSF KFLC/IgG, being this laer (not including serum) more significant. Conclusions : A “kappa- oriented” response characterizes MS and has a prognosc impact in the early disease course.
2

Levraut, Michaël. "Évaluations des chaînes légères libres sériques et intrathécales comme biomarqueur diagnostique et pronostique dans la sclérose en plaques". Electronic Thesis or Diss., Université Côte d'Azur, 2023. http://www.theses.fr/2023COAZ6055.

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La sclérose en plaques (SEP) est la maladie inflammatoire du système nerveux central (SNC) la plus fréquente et est la première cause de handicap d'origine non traumatique dans les populations d'adultes jeunes. Le pronostic neurologique des patients atteints de SEP s'est amélioré ces 20 dernières années grâce à l'avènement des thérapeutiques immuno-actives et les révisions successives des critères diagnostiques, se voulant de plus en plus sensibles. Cependant, ce gain de sensibilité entraîne une diminution de spécificité, avec un risque d'erreurs diagnostiques plus fréquentes. Nous manquons donc d'outils sensible et spécifique d'aide au diagnostic des patients suspects de SEP.Compte tenu des processus immuno-pathologiques impliqués dans la maladie, l'objectif de cette thèse est d'évaluer les performances diagnostiques et pronostiques de différents biomarqueurs dans le liquide céphalo-rachidien (LCR): Différentes cytokines intrathécales (IL-1β, récepteur soluble de l'IL-2 (sIL-2R), IL-6, et IL-10), et les chaînes légères libres (CLL) kappa, en les comparant aux bandes oligoclonales (BOC), actuel biomarqueur du LCR de référence dans la SEP.Nous avons mis en place une cohorte prospective (CyBIRD, NCT05056740) incluant tout patient majeur adressé au CRC-SEP du CHU de Nice pour une suspicion clinique et/ou radiologique de SEP. Sur les 176 patients inclus, l'index kappa et la fraction intrathécale (FI) de CLL kappa favorisaient le diagnostic de SEP (AUC 0.90 et 0.89 respectivement) et les concentrations d'IL-6 et de sIL-2R dans le LCR favorisaient le diagnostic de maladie inflammatoire du SNC non SEP (AUC 0.87 et 0.77 respectivement). Après avoir déterminer les seuils optimaux de chaque biomarqueur, un index kappa positif semblait plus performant que les BOC pour le diagnostic de SEP (AUC 0.82 vs 0.74).Afin de confirmer ces résultats, nous avons mené une seconde étude rétrospective multicentrique française à l'aide du soutien de la Société Francophone de la SEP. Grâce à la collaboration de 13 CRC-SEP français, 1621 patients ont été inclus. Nos résultats montraient que l'index kappa (AUC 0.94) et la FI kappa (AUC 0.94) avaient une capacité diagnostique respectivement équivalente (p=.123), et supérieure à celle de la valeur brute des CLL kappa dans le LCR (AUC 0.91, p<.0001). Un index kappa positif (seuil de 8.9) était plus sensible (88% vs 82%) et aussi spécifique (89% vs 90%) que les BOC. Enfin, la valeur de l'index kappa n'était pas influencée par les caractéristiques cliniques de la maladie, les différentes techniques de dosage des CLL, ou encore la prise de corticoïdes, renforçant son intérêt à la phase diagnostique.Pour terminer, nous avons évalué si la valeur de l'index kappa au diagnostic prédisait l'évolution clinique et radiologique des patients ayant un premier événement clinique suspect de SEP (SCI) ou un syndrome radiologique isolé (SRI). L'étude de 182 patients (146 SCI et 36 SRI) a montré que l'index kappa permettait de prédire l'apparition d'une nouvelle lésion radiologique au cours du temps chez les patients SCI (AUC variant de 0.86 à 0.96 à 12 et 48 mois, Hazard ratio 1.06 [1.04; 1.07], p<.0001) et chez les patients SRI (AUC variant de 0.84 à 0.64 à 12 et 24 mois, Hazard ratio 1.08 [1.03; 1.13], p=.002) mais aussi l'apparition d'une seconde poussée clinique chez les patients SCI (AUC variant de 0.75 à 0.87 à 12 et 48 mois, Hazard ratio 1.04 [1.01; 1.07], p=.007).L'ensemble de nos résultats suggèrent que la mise en évidence d'une synthèse intrathécale de CLL kappa, via le calcul de l'index ou de la FI kappa, est un outil sensible et spécifique pour le diagnostic de SEP. Il permet d'estimer le risque d'évolution clinique et radiologique dès les phases les plus précoces de la maladie. Ces résultats apportent un argument fort pour l'intégration de ce biomarqueur dans les prochaines révisions des critères diagnostiques de la maladie
Multiple sclerosis (MS) is one of the most common central nervous system (CNS) inflammatory and demyelinating disease worldwide, and is the main cause of non-traumatic disability in young adults. Multiple sclerosis prognosis improved during the past 20-years because of treatments development and efficacy and the successive revisions of MS diagnostic criteria that allow to diagnose MS sooner, thanks to their high sensitivity. Nonetheless, the gain in sensitivity in MS diagnostic criteria leads to a loss of specificity increasing the risk of misdiagnosis. We lack sensitive and specific biomarkers that could help clinicians to diagnose MS accurately. Given the pathological processes leading to CNS inflammation in MS, we aimed to evaluate the diagnostic performances of four cytokines implicated in different inflammatory mechanisms (IL-1β, soluble IL-2 receptor (sIL-2R), IL-6, et IL-10) and kappa free light chains (kappa FLC). The performances of all these biomarkers were compared to those of oligoclonal bands (OCB).In Nice University Hospital MS tertiary center, we set up a monocentric prospective cohort (CyBIRD cohort, NCT05056740) that included all adult patients referred for a clinical or MRI suspicion of MS. Of the 176 included patients, both the kappa FLC index and the kappa FLC intrathecal fraction (IF) were able to differentiate MS and non-MS patients (AUC of 0.90 and 0.89 respectively). Cerebrospinal fluid (CSF) IL-6 and sIL-2R concentrations favored non-MS inflammatory CNS disorders (AUC of 0.87 and 0.77 respectively). According to our optimal threshold, a positive kappa FLC index performed better than OB for MS diagnosis (AUC 0.82 vs 0.74).To confirm our results, we conducted, on behalf of the French MS Society, a multicenter retrospective study where 1,621 patients were included. Based on this cohort, the kappa FLC index (AUC 0.94) and the kappa FLC IF (0.94) had similar diagnostic performances (p=.123), higher than the CSF kappa FLC concentration ones (AUC 0.91, p<.0001). A positive kappa FLC index (threshold of 8.9) was more sensitive (88% vs 82%) and as specific as OB (89% vs 90%). We also found that the kappa FLC index value was not influenced by baseline MS clinical characteristics, by samples or analyzers differences, nor by steroid exposure at sampling reinforcing its interest as diagnostic biomarker.Finally, we evaluated whether the baseline value of the kappa FLC index was able to predict clinical relapses or new MRI lesions during follow-up, in patients presenting with clinically or radiologically isolated syndromes (CIS and RIS). Based on the retrospective study of 182 patients (146 CIS and 36 RIS), the kappa FLC index was able to predict new MRI lesions in CIS (AUC of 0.86 and 0.96 at 12 and 48 months respectively - Hazard ratio of 1.06 [1.04; 1.07], p<.0001), and in RIS (AUC of 0.84 and 0.64 at 12 and 24 months respectively - Hazard ratio of 1.08 [1.03; 1.13], p=.002), but also clinical relapse in CIS (AUC of 0.75 and 0.87 at 12 and 48 months respectively - Hazard ratio of 1.04 [1.01; 1.07], p=.007).Our results suggest that a kappa FLC CSF-restricted synthesis (kappa FLC index or IF) is sensitive and specific for MS diagnosis, and may predict clinical and MRI disease course in the earliest phases of the disease. Therefore we suggest adding kappa FLC biomarkers (whether it is kappa FLC index or IF) in the further revisions of MS diagnostic criteria
3

Basnayake, Kolitha Indika. "The biology of immunoglobulin free light chains in kidney disease : a study of Monoclonal and Polyclonal light chains". Thesis, University of Birmingham, 2012. http://etheses.bham.ac.uk//id/eprint/2862/.

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Monoclonal immunoglobulin free light chains (FLCs) cause a range of disorders in the kidney. In multiple myeloma, FLCs can activate the proximal tubule to release MCP-1, an important cytokine in renal fibrosis. Distal tubular cast formation can also occur when FLCs co-precipitate with uromodulin. However a pathogenic role for the elevated polyclonal FLC concentrations seen in chronic kidney disease has not been assessed to date. This thesis explores the biology of monoclonal FLCs as well as polyclonal FLCs. Detailed histological analyses demonstrated that in multiple myeloma, interstitial fibrosis can progress rapidly in situ and indicated that intratubular cast numbers might be linked to potential for renal recovery. The functional basis of this fibrosis was explored by in vitro studies, which showed that upon endocytosis of FLCs, oxidative stress activated redox signalling, resulting in MCP-1 production. Further in situ analyses showed that in chronic kidney disease, polyclonal FLCs co-localised with uromodulin in distal tubular casts. Relationships between these casts and markers of progression of chronic kidney disease were demonstrated. In vitro analyses then showed that polyclonal FLCs bind to uromodulin and promote aggregation. These findings: (i) further delineate the pathways for proximal tubular injury in myeloma and (ii) indicate a potential pathogenic role for polyclonal FLCs in the distal nephron.
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Housden, Nicholas George. "Characterisation of pre-equilibrium and equilibrium binding interactions between Peptostreptococcal protein L and human kappa light chains". Thesis, University of Southampton, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273801.

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Rimsza, Lisa, William Day, Sarah McGinn, Anne Pedata, Yasodha Natkunam, Roger Warnke, James Cook, Teresa Marafioti y Thomas Grogan. "Kappa and lambda light chain mRNA in situ hybridization compared to flow cytometry and immunohistochemistry in B cell lymphomas". BioMed Central, 2014. http://hdl.handle.net/10150/610134.

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BACKGROUND:Detection of B cell clonality is useful for assisting in the diagnosis of B cell lymphomas. Clonality assessment can be accomplished through evaluation of KAPPA and LAMBDA light chain expression. Currently, only slide based methods are available for the majority of patient biopsies and do not detect light chain protein or mRNA in many B-cell lymphomas. Herein we evaluated a new method, known as colorimetric in situ hybridization (CISH), with improved sensitivity and multiplexing capacity, for its usefulness in clonality detection in mature B cell malignancies.METHODS:The KAPPA and LAMBDA ISH was performed on a Ventana Benchmark XT utilizing two color chromogenetic detection. The probes comprised 2 haptenated riboprobes each approximately 500 base pairs long directed against the conserved regions of either KAPPA or LAMBDA mRNA. The dual colors consisted of silver deposition (black) for KAPPA light chain and a novel (pink) chromogen for LAMBDA light chain. Following optimization, CISH allowed visualization of mRNA in benign B cells in reactive tissues including germinal center, mantle zone, and post-germinal center cells. We then identified 79 cases of B cell lymphoma with formalin-fixed paraffin-embedded (FFPE) biopsies including: follicular (36 cases), mantle cell (6 cases), marginal zone (12 cases), lymphoplasmacytic (6 cases), small lymphocytic (4 cases), and diffuse large B cell (15 cases), which were selected on the basis of either prior flow cytometry or immunohistochemistry (IHC) results to serve as the predicate, "gold standard," comparator.RESULTS:39/79 (49.4%) cases were classified as KAPPA and 29/79 (36.7%) as LAMBDA light chain restricted
while 9/79 (11.3%) cases were classified as indeterminate. Of the 70 cases with KAPPA or LAMBDA light chain restricted CISH, 69/70 (98.6%) were concordant with the reference method, while 1/70 (1.4%) was discordant.CONCLUSIONS:Optimized CISH detected lower levels of mRNA than can be visualized with current slide based methods, making clonality assessment in FFPE biopsies possible for mature B cell neoplasms. In this preliminary study, CISH was highly accurate compared to flow cytometry or IHC. CISH offers the possibility of wider applicability of light chain ISH and is likely to become a useful diagnostic tool.Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1430491067123856
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Germishuys, Jurie J. "Free light chains in patients with HIV: establishing local reference ranges and their association with stage of disease, chronic antigen stimulation and the effect of Haart". Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/20173.

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Thesis (MMedSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: Background: Serum free light chains (FLC) are associated with imbalances in heavy and light chain production. Abnormal FLC ratios have been associated with risk of progression in certain diseases. Automated assays are available for their determination and they are used in the followup and management of patients with monoclonal gammopathies. Acceptable imprecision, specificity, accuracy and reproducibility between reagent batches is required to prevent under- or overestimation. Method validation is a standard process in every good laboratory to judge the acceptability of a new method. Reference intervals have been established in an older population, but it was considered important to verify these in our population. HIV is associated with B-cell dysfunction. As B-cell abnormalities are associated with disorders leading to monoclonal gammopathies, we postulated that the FLC levels and FLC ratio would be abnormal in HIV infected individuals. Methods and materials: Controls and pooled patient samples were used for the method validation study which included imprecision studies, linearity, recovery and interference studies, and method comparison studies, the latter compared our method to the same method used in another laboratory. For the reference interval study, blood was obtained from 120 healthy subjects. The following blood tests were performed: total protein, IgG, IgA, IgM, creatinine, protein electrophoresis, kappa FLC and lambda FLC. Using the kappa and lambda FLC results, a FLC ratio was determined. Three hundred and sixty-nine HIV positive subjects were then studied. The same tests were performed, as well as CD4+ counts and viral loads on the majority of them. Results: For the method validation study, precision, linearity and recovery was acceptable. Minimal interference was observed with haemolysis, lipaemia, bilirubin and rheumatoid factor. Our method showed comparable performance with the established method. For the reference interval study, all the creatinine values were normal, as were serum protein values. The serum protein electrophoreses were independently reviewed by 3 pathologists. Most were normal, with a few polyclonal increases seen, but no definite monoclonal bands. The 95% reference intervals for FLC’s as well as the FLC ratio were not statistically significantly different to the manufacturer’s recommendations. When examining the HIV positive study population, we found that FLC and FLC ratio were influenced by markers of HIV disease severity, such as CD4+ count, IgG, viral load, use of antiretroviral treatment and abnormal serum protein electrophoreses. Conclusion: The validation study of FLC showed excellent precision, acceptable bias, good linearity, good recovery and minimal interference, allowing routine introduction of the test. The 95% reference intervals obtained for our population were slightly higher than those recommended by the manufacturer. However, as most of the values fell within the manufacturer’s limits, we could accept the manufacturer’s recommended cut-offs. We found that FLC levels were definitely influenced by markers of HIV disease severity in our population and we postulate that they may be of use for follow-up of patients with HIV.
AFRIKAANSE OPSOMMING: Agtergrond: Serum vry ligte kettings (VLK) word geassosieer met ‘n wanbalans van ligte en swaar ketting produksie. Abnormale VLK ratios is geassosieer met ‘n risiko van verloop in sekere siektes. Geoutomatiseerde laboratorium toetse vir VLK is beskikbaar vir hul bepaling en word gebruik om pasiënte met monoklonale gammopatieë op te volg en te behandel. Aanvaarbare impresisie, spesifisiteit, akkuraatheid en herhaalbaarheid tussen reagens besendings is belangrik om onder- of oorbepaling te verhoed. Metode validasie is ’n standaard proses in elke goeie laboratorium om die aanvaarbaarheid van ’n nuwe metode te bepaal. Verwysingswaardes is al bepaal in ’n ouer populasie. Ons het besluit om die verwysingswaardes in ons populasie te bepaal. Mens-immuungebrekvirus (MIV) word geassosieer met B-sel disfunksie. Omdat B-sel abnormaliteite geassosieer word met afwykings wat tot monoklonale gammopatieë lei, het ons gepostuleer dat die VLK vlakke en VLK ratio abnormaal sal wees in MIV geïnfekteerde persone. Metodes en Materiale: Kontroles en pasiënt monsters is gebruik vir die metode validasie studie wat impresisie studies, lineariteit, herwinning, inmenging en metode korrelasie studies ingesluit het. In laasgenoemde geval is ons metode met dieselfde metode van ’n ander laboratorium vergelyk. Vir die verwysingswaardes studie is 120 gesonde persone se bloed gebruik. Die volgende toetse is bepaal: totale proteïen, IgG, IgA, IgM, kreatinien, proteïen elektroferese, kappa en lambda VLK. Die VLK ratio is bepaal deur die kappa en lambda resultate te gebruik. Driehonderd nege en sestig MIV-positiewe pasiente is gebruik vir die studie. Dieselfde toetse was gedoen, asook CD4+ tellings en virale ladings op die meerderheid van pasiente. Resultate: Vir die metode validasie studie, was presisie, lineariteit en herwinning aanvaarbaar. Minimale inmenging van hemolise, lipemie, bilirubien en rumatoïede factor is waargeneem. Ons metode het goed gekorreleer met die bepaalde metode. Die serum kreatinien en serum totale proteïen waardes was normaal tydens die verwysingswaardes studie. Die serum proteïen elektroferese was onafhanklik beoordeel deur 3 patoloë. Die meeste was normaal met enkele poliklonale verhogings, maar geen definitiewe monoklonale bande nie. Die 95% verwysings intervalle vir VLK en VLK ratio het nie statisties betekenisvol verskil van die vervaardiger se aanbevelings nie. In die studie van die MIV-positiewe studie populasie, het ons gevind dat VLK en VLK ratio beïnvloed word deur merkers van ernstige MIV siekte, soos CD4+ telling, IgG, virale lading, die gebruik van antiretrovale medikasie en abnormale serum proteïen elektroferese. Gevolgtrekking: Die validasie studie van VLK het uitstekende presisie, aanvaarbare partydigheid, goeie lineariteit, goeie herwinning en minimale inmenging gewys, wat die roetine instelling van die toets toegelaat het. Die 95% verwysingsintervalle wat vir ons populasie bepaal is, was effens hoër as die vervaardiger se aanbeveling. Die meeste van die waardes het egter binne die vervaardiger se limiete geval, dus kon ons die vervaardiger se afsnypunte aanvaar. Ons het gevind dat VLK vlakke definitief beïnvloed word deur merkers van die ernstigheidsgraad van MIV siekte in ons populasie en ons postuleer dat VLK van waarde kan wees met die opvolg van MIV pasiente.
NHLS
Harry Crossley for funding obtained
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Frölich, Britta. "Bedeutung freier Leichtketten im Urin bei Patienten mit chronisch entzündlicher rheumatischer Erkrankung". Doctoral thesis, 2018. http://hdl.handle.net/11858/00-1735-0000-002E-E429-9.

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Libros sobre el tema "Kappa free light chains":

1

Bradwell, A. R. Serum free light chain analysis: (plus Hevylite). 5a ed. Birmingham: Binding Site Ltd., 2008.

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2

Kuypers, Dirk R. J. y Morie A. Gertz. Light-chain deposition disease. Editado por Giuseppe Remuzzi. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0154_update_001.

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Light-chain deposition disease (LCDD) is characterized by extracellular tissue deposition of non-amyloid monoclonal immunoglobulin light chains (predominantly kappa light chains) in various organs including kidneys, heart, and liver. It is a rare cause of renal insufficiency. In two-thirds of cases it is associated with multiple myeloma, while in the remainder their monoclonal B cell proliferation does not meet the criteria for that diagnosis.Renal involvement occurs almost invariably and dominates the clinical course of the disease: greater than 90% of patients with LCDD have renal functional impairment; acute or rapidly progressive kidney failure usually develops over a period of months. Nephrotic-range proteinuria is present in 40–50% of patients while approximately 20% of patients develop nephrotic syndrome. Arterial hypertension and microscopic haematuria can be present. Extrarenal symptoms are related to affected organs with cardiomyopathy, cachexia, haemorrhages, infections, and MM progression as main causes of death.The diagnosis of LCDD is often delayed and whilst bone marrow examination will often identify associated MM, renal biopsy frequently provides the final diagnostic proof. Abnormal light chains can be detected and quantified by serum or urine protein electrophoresis and immunofixation. Quantification of urine and serum free kappa/lambda light chains has proven a useful screening tool and might also plays a role in therapeutic monitoring.Treatment consists of chemotherapy directed against the monoclonal immunoglobulin-producing plasma cells.
3

Anderson, Michael Thomas. Studies of the regulation of the immunoglobulin kappa light chain intron enhancer. 1990.

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4

A.R., MB ChB, FRCP, FRCPath Bradwell. Serum free light chain analysis. The Binding Site, 2006.

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5

Eastmead, Stephen P. Enzyme immunoassay of human free immunoglobin light chains. 1985.

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6

Chou, Calvin L. Molecular analysis of the myeloma W3129 and derived mutants: Insertion of a novel sequence and subsequent partial deletion affect immunoglobulin kappa light chain expression. 1992.

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7

Gallaher, Katie y José de la Cruz. Butterflies Set Free: Breaking the Chains of 21st-Century Slavery by Bringing It into the Light. Independently Published, 2022.

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8

Kastritis, Efstathios y Meletios A. Dimopoulos. The patient with myeloma. Editado por Giuseppe Remuzzi. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199592548.003.0153_update_001.

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Renal impairment is a common feature of multiple myeloma and often the presenting symptom of a patient with symptomatic myeloma. ‘Myeloma kidney’ results from the excess of immunoglobulin light chains which form aggregates and casts that result in tubular obstruction; however, light chains may cause renal damage with a variety of mechanisms, which often may coexist in the same patient. The presence of significant renal dysfunction in a patient with myeloma is associated with a risk for significant complications, including early death. Myeloma kidney is usually associated with high tumour burden and high rates of paraprotein production.Patients with renal impairment should be managed immediately with appropriate antimyeloma therapy and supported vigorously. New drugs such as bortezomib are probably the most effective therapies for patients with renal dysfunction and may improve renal function in a significant proportion of patients with myeloma-related renal impairment, especially with dexamethasone at high doses. Other drugs such as thalidomide or lenalidomide may also be helpful in certain patients. Direct removal of the toxic free light chains may improve outcomes in some patients, but randomized studies are still ongoing. The role of plasmapheresis has not been established.Autologous stem cell transplantation, with appropriate dose adjustments for high-dose melphalan should be offered in eligible patients, even those on dialysis, although this procedure may be associated with a higher risk of toxicity in patients with more severe renal dysfunction. Renal transplantation may be an option for selected patients who have responded well to therapy.

Capítulos de libros sobre el tema "Kappa free light chains":

1

Cohen, Gerald y Walter H. Hörl. "Free Immunoglobulin Light Chains". En Uremic Toxins, 279–91. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2012. http://dx.doi.org/10.1002/9781118424032.ch18.

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Fouquet, Guillemette, Stéphanie Poulain, Suzanna Schraen, Efstathios Koulieris, Elisabeth Bertrand, Stéphanie Guidez, Cécile Tomowiak et al. "Laboratory Investigations and Findings: Hematological Abnormalities, Biochemical Investigations, Free Light and Heavy Chains". En Waldenström’s Macroglobulinemia, 239–61. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-22584-5_17.

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Sindic, C. J. M. "The detection of IgA, IgM and free light chains abnormalities in cerebrospinal fluid". En Cerebrospinal Fluid Analysis in Multiple Sclerosis, 41–50. Milano: Springer Milan, 1996. http://dx.doi.org/10.1007/978-88-470-2205-8_4.

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Mayo, Mary M. y Gretchen Schaef Johns. "Serum Free Light Chains in the Diagnosis and Monitoring of Patients with Plasma Cell Dyscrasias". En Contributions to Nephrology, 44–65. Basel: KARGER, 2006. http://dx.doi.org/10.1159/000096760.

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Paternoster, Gianluca, Paolo Fabbrini y Imma Attolico. "Extracorporeal Removal of Serum-Free Light Chains in Patients with Multiple Myeloma-Associated Acute Kidney Injury". En Reducing Mortality in Acute Kidney Injury, 143–48. Cham: Springer International Publishing, 2016. http://dx.doi.org/10.1007/978-3-319-33429-5_17.

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Toft, K. G., O. K. Olstad, K. Sletten y P. Westermark. "Comparative Studies of Two AL Chains of Kappa-III Light Chain Origin with and without Attached Carbohydrate (AL So124 and AL 700)". En Amyloid and Amyloidosis 1990, 169–72. Dordrecht: Springer Netherlands, 1991. http://dx.doi.org/10.1007/978-94-011-3284-8_42.

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Rudick, Richard A. "Free Light Chains of Immunoglobulins in Multiple Sclerosis: A Putative Index of the Intrathecal Humoral Immune Response". En Cellular and Humoral Immunological Components of Cerebrospinal Fluid in Multiple Sclerosis, 187–200. Boston, MA: Springer US, 1987. http://dx.doi.org/10.1007/978-1-4899-5348-3_23.

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Hegen, Harald y Florian Deisenhammer. "Oligoclonal Bands: Isoelectric Focusing and Immunoblotting, and Determination of κ Free Light Chains in the Cerebrospinal Fluid". En Neuromethods, 29–54. New York, NY: Springer US, 2021. http://dx.doi.org/10.1007/978-1-0716-1319-1_3.

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Willrich, Maria Alice V. y Ruba S. Saadeh. "New-Onset Gait Difficulty With Kappa Free Light Chains in Cerebrospinal Fluid". En Mayo Clinic Cases in Neuroimmunology, editado por Andrew McKeon, B. Mark Keegan y W. Oliver Tobin, 42–43. Oxford University Press, 2021. http://dx.doi.org/10.1093/med/9780197583425.003.0013.

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A 49-year-old woman sought care for a 9-month history of gait difficulty. She was dragging her right foot when walking and could not walk more than 3 blocks because of right leg weakness. Physical examination showed right-sided weakness of hip flexion and foot dorsiflexion and symmetrical hyperreflexia at the knees and ankles. Magnetic resonance imaging of the brain showed multiple foci of T2 hyperintensity throughout the white matter in both cerebral and cerebellar hemispheres, predominantly in a periventricular distribution. Several small enhancing lesions and mild generalized cerebral volume loss were seen. The appearance and distribution were consistent with a demyelinating process such as multiple sclerosis. Magnetic resonance imaging of the cervical and thoracic spine showed multiple small T2 hyperintensities, including 1 enhancing lesion in the cervical spinal cord. Oligoclonal bands were positive, with 11 unique bands in the cerebrospinal fluid. The concentration of cerebrospinal fluid kappa free light chains was increased, at 0.314 mg/dL. The patient was diagnosed with relapsing-remitting multiple sclerosis. A 5-day course of intravenous corticosteroids was started, after which she noted clinical improvement. At her last follow-up 2 years after initial evaluation, the patient has been stable with no new clinical multiple sclerosis episodes and stable magnetic resonance imaging disease burden with no new lesions. The diagnosis of multiple sclerosis incorporates clinical, imaging, and laboratory evidence. The 2017 revised McDonald criteria state that a finding of cerebrospinal fluid -specific oligoclonal bands can replace the criterion for dissemination in time to make a diagnosis of definitive multiple sclerosis. The standard test for oligoclonal bands is performed using isoelectric focusing electrophoresis and takes more than 3 hours to complete. The case patient had 11 unique cerebrospinal fluid bands. The number of bands is not correlated with disease severity or prognosis.
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van Steijn, J., J. Bijzet, H. de Wit, B. P. C. Hazenberg, I. I. van Gameren, K. van de Belt y E. Vellenga. "Serum Levels of Free Kappa and Lambda Light Chains in Patients with Systemic AL, AA, and ATTR Amyloidosis". En Amyloid and Amyloidosis, 105–6. CRC Press, 2004. http://dx.doi.org/10.1201/9781420037494-37.

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Actas de conferencias sobre el tema "Kappa free light chains":

1

Tent, Michiel. "Cerebrospinal fluid kappa-free light chains for MS diagnosis". En ECTRIMS Congress 2022, editado por Hans-Peter Hartung. Baarn, the Netherlands: Medicom Medical Publishers, 2022. http://dx.doi.org/10.55788/5ddc21fc.

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Senne, Carlos, Carlos Giaffer, Marcio Vega, Daiane Salomão y Renan Domingues. "Kappa index and oligoclonal bands detection in cerebrospinal fluid samples of patients with suspected multiple sclerosis". En XIV Congresso Paulista de Neurologia. Zeppelini Editorial e Comunicação, 2023. http://dx.doi.org/10.5327/1516-3180.141s1.741.

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Introduction: The evaluation of the intrathecal production of immunoglobulin G (IgG) can be useful in the evaluation of multiple sclerosis (MS) suspected cases and the most important test to verify it is the detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) and serum. Recent studies have reported that measuring CSF IgG free light chains (FLC), especially the Kappa Index, is comparable with OCBs as markers of IgG synthesis. It is still unknown if diagnostic sensitivity be increased by performing these two methods in parallel. Objectives: The aim of this study was to evaluate the results of the Kappa index and the oligoclonal bands (BOCs) in samples from patients with suspected MS. Methods: Patients with suspected MS underwent CSF analysis. Intrathecal synthesis of IgG was evaluated with BOCs, IgG index, Reiber nomogram, and kappa index. Results: One hundred and seventy-one serum and CSF samples were included, 76 of them had positive CSF BOC. Among the BOC+ cases, 48 (63.2%) were also positive with the Reiber nomogram, 53 (69.7%) were also positive with the IgG index, and 74 (97.4%) were also positive with the kappa index. Among the patients without BOCs, 5 (5.2%) cases had a positive Reiber, eight had a positive IgG index (8.4%), and eight (8.4%) had a positive kappa index. Conclusion: The Kappa index was the method with the highest association with BOCs, confirming that this method is at least as sensitive as the detection of BOCs. Positive kappa results found among cases without BOCs may be false positives but may also indicate false negative results with BOC. Therefore, it is possible that kappa index can help to diagnose cases of MS without detection of BOCs.
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Rodriguez Cambron, A. B., J. Jimenez Jimenez, M. A. Blazquez Cañamero, M. J. García De Yébenes, F. Rey Pazos, C. Macía Villa, F. M. Alcalde Villar et al. "FRI0344 Serum free light chains as a flare biomarker in systemic lupus erythematosus". En Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.5374.

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Belghali, S., S. Lataoui, S. Ferchichi, K. Baccouche, N. Elamri, K. Limam, H. Zeglaoui y E. Bouajina. "FRI0165 Serum free light chains of immunoglobulins in rheumatoid arthritis: correlation with interstitial lung disease". En Annual European Congress of Rheumatology, 14–17 June, 2017. BMJ Publishing Group Ltd and European League Against Rheumatism, 2017. http://dx.doi.org/10.1136/annrheumdis-2017-eular.6364.

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Amin, S., E. J. Atkinson, S. J. Achenbach, A. Dispenzieri, R. A. Kyle y S. V. Rajkumar. "THU0470 Non-clonal elevation of serum immunoglobulin free light chains is predictive of hip fracture in both women and men". En Annual European Congress of Rheumatology, EULAR 2018, Amsterdam, 13–16 June 2018. BMJ Publishing Group Ltd and European League Against Rheumatism, 2018. http://dx.doi.org/10.1136/annrheumdis-2018-eular.6041.

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6

Kos, M., K. Geibler, K. Ratheiser, I. Pabinger, Ch Korninger y K. Lechner. "ACQUIRED FACTOR X DEFICIENCY IN MULTIPLE MYELOMA:A COMPLETE RESPONSE TO CHEMOTHERAPY." En XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643292.

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A 64 year old women without any previous history of bleeding diathesis presented with bone pain and gastrointestinal bleeding. An isolated severe factor X deficiency (factor X activity 0.5%, factor X antigen less than 12.5%) was found. No inhibitor that inactivated factor X in vitro or interfered with factor X assay could be demonstrated. Substitution therapy with a prothrombin complex preparation containing factor X (PPSB Biotest) was given. Factor X recovery in the first 2 days was lower than expected (below 20%) and half life of factor X was shortened (150 minutes). Subsequently, a diagnosis of multiple myeloma (light chain myeloma, type kappa) was made. Amyloidosis was excluded by electronmicroscopic examination of rectum biopsies. Chemotherapy according to the M2 protocol (Case et al) was initiated. Factor X recovery improved dramatically within 2 weeks and there was a continuous increase of factor X activity and antigen during chemotherapy. After 6 courses a complete haematological remission (less than 5% plasma cells in the bone marrow, disappearance of light chains) was obtained and factor X activity and antigen returned to normal.Isolated factor X deficiency is a wellknown complication of amyloidosis. To our knowledge, this is the first case of factor X deficiency in multiple myeloma without amyloidosis. The complete normalization of factor X after successful chemotherapy indicates that plasma cell proliferation may have been the cause of the factor X deficiency. Binding of factor X to plasma cells containing light chains could be a possible explanation, and we are currently examining this hypothesis.
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Hu, Wei, Ola Landgren, Bryan Bassig, Mark Purdue, Eric Engels, Qing Lan y Nathaniel Rothman. "Abstract 5074: Elevated serum free light chains and risk of non-Hodgkin lymphoma and the subtype follicular lymphoma in a prospective cohort study". En Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA. American Association for Cancer Research, 2014. http://dx.doi.org/10.1158/1538-7445.am2014-5074.

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Ishiguro, H., S. Higashiyama, C. Namikawa, I. Ohkubo y M. Sasaki. "MAPPING OF FUNCTIONAL DOMAINS OF HUMAN HIGH MOLECULAR WEIGHT (HMW) AND LOW MOLECULAR WEIGHT (LMW) KININOGENS BY USING MURINE MONOCLONAL ANTIBODIES (MAbs)". En XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642849.

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It has been widely known that HMW and LMW kininogens are the large potential sources of kinin in human blood, and that HMW kininogen also functions as a cofactor in the contact activation of blood coagulation. Recently, it has been demonstrated that the heavy chains of kininogens strongly inhibited a number of cysteine proteinases such as calpains, cathepsins, papain and ficin. We made an attempt at mapping of functional domains on the molecules of both kininogens by using MAbs.Thirty four MAbs raised against human HMW and LMW kininogens were screened by ELISA. By using HMW kininogen, kinin-free HMW kininogen, kinin and fragment 1.2 (fr 1.2)-free HMW kininogen, LMW kininogen, kinin-free LMW kininogen, heavy chain of LMW kininogen and light chains of both kininogens, the MAbs were characterized and.classified into four groups; [1] 20 MAbs reacted with heavy chain, a common region of HMW and LMW kininogens. These MAbs possessed the specificity for domain 1 (2 MAbs), domain 2 (2 MAbs), domain 3 (7 MAbs), and both domains 2 and 3 (7 MAbs) of the heavy chain; [2] 7 MAbs recognized the fr 1.2, a unique histidine-rich region; [3] 5 MAbs reacted with the light chain of HMW kininogen; [4] 2 MAbs recognized the light chain of LMW kininogen.Two MAbs, designated HKG H7 and H12, effectively inhibited the cysteine proteinase inhibitor activity of HMW and LMW kininogens and the others did not affect it. Further, the MAbs, which recognized the fr 1.2 or light chain of HMW kininogen, suppressed the clotting activity. Especially, 2 MAbs, named HKG L2 and L5, effectively suppressed the clotting activity of HMW kininogen. The former, which neutralized about 70% of the clotting activity, reacted specifically with fr 1.2 region of HMW kininogen, and the latter, which neutralized more than 90% of it, recognized the light chain of HMW kininogen. In the results of competition ELISA, fr 1.2 specific MAbs could be classified into 5 kinds of MAbs for recognition sites, and the light chain (HMW kininogen)-specific MAbs also could be classified into 3 kinds of MAbs. Further, 2 light chain (LMW kininogen)-specific MAbs were thought to recognize an identical antigenic site.
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Hatami-Marbini, Hamed y Ebitimi Etebu. "Influence of Ionic Concentration on Swelling Behavior and Shear Properties of the Bovine Cornea". En ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80896.

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The mechanical properties and structure of connective tissues such as the cornea and the cartilage are derived from the functions and properties of their extracellular matrix, a polyelectrolyte gel composed of collagenous fibers embedded in an aqueous matrix. The collagen fibers in the extracellular matrix of the corneal stroma are arranged in regular lattice structures, which is necessary for corneal transparency and transmitting the incident light to the back of the eye. This regular pseudo hexagonal arrangement is attributed to the interaction of collagen fibers with the proteoglycans as these regularities are lost in knock-out mice [i]. Proteoglycans (PGs) are heavily glycosylated glycoproteins. They consist of a core protein to which is glycosaminoglycan chains are covalently attached. The main PG in the corneal stroma is the proteoglycan decorin. Decorin is the simplest small leucine-rich PG and only has a single glycosaminoglycan side chain. It has a horse shape core protein and binds collagen fibrils at regular sites. Chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) are among the prevalent glycosaminoglycans found in the cornea. Under physiological conditions, these linear carbohydrate polymers are ionized and carry negative charges due to the presence of negatively charged carboxylate and sulfate groups. Therefore, a hydrated gel is formed in the empty space between collagen fibrils by attracting water. The interaction of negatively charged glycosaminoglycans with themselves and their interaction with the free ions contribute to the corneal swelling pressure and subsequently to its compressive stiffness. From structural view point, the corneal stroma is a composite polyelectrolyte system in which the observed regular spacings of the collagens are suggested to exist because of the structural interaction of collagens, negatively charged glycosaminoglycans, and the free ions in the interfibrillar space.

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