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1

Avet-Loiseau, Hervé, Richard Garand, Laurence Lodé, Jean-Luc Harousseau, and Régis Bataille. "Translocation t(11;14)(q13;q32) is the hallmark of IgM, IgE, and nonsecretory multiple myeloma variants." Blood 101, no. 4 (February 15, 2003): 1570–71. http://dx.doi.org/10.1182/blood-2002-08-2436.

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In an attempt to address the issue of cytogenetic features of multiple myeloma (MM) variants, we have analyzed a series of 8 IgM, 9 IgD, 2 IgE, and 14 nonsecretory (NS) MM cases using fluorescence in situ hybridization. A very high incidence (83%) of t(11;14)(q13;q32) was detected in the IgM (7 of 8), IgE (2 of 2), and NS (11 of 14) MM cases, but not in the IgD cases (2 of 9). Of note, no t(4;14) was observed in this cohort of patients. This increased incidence of t(11;14) was associated with 2 dominant features in these variants, namely, a “lymphoplasmacytic” presentation mainly in IgM MM and a lower secreting capacity in the others, 2 features previously associated with t(11;14). Of major interest, t(11;14) was never observed in Waldenström macroglobulinemia or in IgG/IgA “lymphoplasmacytic” lymphomas. Thus, for unknown reasons, t(11;14) is the hallmark of IgM, IgE, and NS MM, (but not IgD MM), with a 5-fold increase of its incidence compared to that of IgG and IgA MM.
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2

Kolopp-Sarda, M. N., and G. C. Faure. "Pourquoi les immunoglobulines s’appellent-elles IgG, IgA, IgM, IgD et IgE ?" Revue Francophone des Laboratoires 2016, no. 484 (July 2016): 57–58. http://dx.doi.org/10.1016/s1773-035x(16)30250-7.

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3

Sharma, R., and Z. Woldehiwet. "Class-specific antibodies to bovine respiratory syncytial virus in experimentally infected lambs." Epidemiology and Infection 108, no. 1 (February 1992): 135–45. http://dx.doi.org/10.1017/s095026880004958x.

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SUMMARYEnzyme-linked immunoabsorbent assay (ELISA) was used to titrate virus-specific IgG, IgM and IgA levels in nasal secretions, lung lavage fluids and serum samples sequentially obtained from lambs experimentally infected with bovine respiratory syncytial virus (RSV). Virus-specific IgG and IgM responses were measured by the indirect double antibody sandwich ELISA using anti-bovine RSV monoclonal antibody, as capture antibody, and peroxidase-conjugated anti-sheep IgG and anti-sheep IgM. Virus-specific IgA antibodies were measured by antibody capture assay using anti-sheep IgA (α–chain specific) and anti-bovine RSV monoclonal antibodies.Bovine RSV-specific IgM and IgA antibodies were detected in the serum samples within 6 days post-inoculation (p.i.). Virus-specific IgC antibodies appeared in serum samples 4 days later. In nasal secretions, IgA antibodies appeared 7 days p.i. but IgM antibodies were not detected until 12–16 days p.i. In serum samples, IgM titres were predominant for the first 2 weeks p.i. IgC titres becoming predominant thereafter. In nasal secretions and lung lavage fluids, IgA titres were significantly higher than IgM or IgG titres up to 21 days p.i. (0·01).
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4

Singh, Desh D., L. K. Dwivedi, Sarika Amdekar, and Vinod Singh. "The Immunoglobulin profiling of Schistosoma mansoni infected patients from Central India." South Asian Journal of Experimental Biology 1, no. 5 (December 6, 2011): 32–35. http://dx.doi.org/10.38150/sajeb.1(5).p32-35.

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Schistosoma mansoni ‐schistosomicimmune response in them. Also, an attempt was made to correlate the observedIg level with the brutality of infection. Consequently, total 138(46.9%) out of 294 volunteers were reported to have ova of Schistosomamansoni in their urine samples. Among which, 84 (28.6%) volunteers with<50 ova in per 10 ml of urine showed light infection while remaining 54(18.4%) volunteers with >50 ova in per 10 ml of urine showed heavy infection.This difference was found statistically significant (X 2= 6.52, p > 0.05).The mean immunoglobulin status observed in their serum sample were; IgE(2141.6 ± 143.7 mg/dL), IgG (13.6 ± 3.53 mg/dL), IgA (3.72 ± 0.149 mg/dL),IgM (2.82 ± 0.48 mg/dL) and IgD (0.12 ± 0.04 mg/dL). The relationship betweenintensity of infection and serum level of IgM & IgE were positivelycorrelated (r =0.27 and r =0.65, respectively) while IgG, IgA and IgD wereshowing negative correlation with the strength of infection (r = ‐0.65, r = ‐0.39 and r = ‐0.18, respectively). Therefore, IgG and IgA can be considered asmarkers of light infection and IgM and IgE for heavy infection respectively.Since, the levels of IgG, IgA and IgD were found very low in infected volunteersthan control subjects hence, are suggested to play insignificant protectiverole in schistosomic infection., a trematode is a significant parasite of human beingscausing intestinal schistosomiasis. In the present investigation, 294 volunteersfrom central India were screened for schistosomic infection, and theserum immunoglobulin (Ig) levels were calculated as an anti
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Harfi, Harb A., and John T. Godwin. "Normal Serum Levels of IgG, IgA, IgM, IgD, and IgE in Saudi Arabia." Annals of Saudi Medicine 5, no. 2 (April 1985): 99–104. http://dx.doi.org/10.5144/0256-4947.1985.99.

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Salonen, Eeva-Marjatta, Tapani Hovi, Olli Meurman, Timo Vesikari, and Antti Vaheri. "Kinetics of specific IgA, IgD, IgE, IgG, and IgM antibody responses in rubella." Journal of Medical Virology 16, no. 1 (May 1985): 1–9. http://dx.doi.org/10.1002/jmv.1890160102.

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7

Collin, Mattias, and Arne Olsén. "Effect of SpeB and EndoS from Streptococcus pyogenes on Human Immunoglobulins." Infection and Immunity 69, no. 11 (November 1, 2001): 7187–89. http://dx.doi.org/10.1128/iai.69.11.7187-7189.2001.

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ABSTRACT Streptococcus pyogenes secretes a specific immunoglobulin G (IgG)-protease, SpeB, as well as the IgG glycan-hydrolyzing enzyme EndoS. Here we show that SpeB also degrades IgA, IgM, IgD, and IgE. We also show that EndoS only hydrolyzes the glycan moiety on native but not denatured IgG. Thus, SpeB has a broad immunoglobulin-degrading activity, while EndoS is highly specific for IgG.
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8

Creasey, Alison M., Trine Staalsoe, Ahmed Raza, David E. Arnot, and J. Alexandra Rowe. "Nonspecific Immunoglobulin M Binding and Chondroitin Sulfate A Binding Are Linked Phenotypes of Plasmodium falciparum Isolates Implicated in Malaria during Pregnancy." Infection and Immunity 71, no. 8 (August 2003): 4767–71. http://dx.doi.org/10.1128/iai.71.8.4767-4771.2003.

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ABSTRACT Binding of immunoglobulin M (IgM) antibodies from normal human serum to the surface of Plasmodium falciparum-infected red blood cells (iRBC) has previously been demonstrated only in parasites that form rosettes with uninfected red cells. We show that natural, nonspecific IgM but not IgG, IgA, IgD, or IgE also binds to the surface of iRBC selected for adhesion to chondroitin sulfate A (CSA), a placental receptor for parasites associated with malaria in pregnancy. The protease sensitivity of IgM-binding appears to match that of CSA binding, suggesting that the two phenotypes may be mediated by the same parasite molecule. We also show that a wide range of mouse monoclonal antibodies of the IgM class bind nonspecifically to CSA-selected iRBC, an important consideration in the interpretation of immunological assays performed on these parasite lines.
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9

Anam, Khairul, Farhat Afrin, Dwijadas Banerjee, Netai Pramanik, Subhasis K. Guha, Rama P. Goswami, Shiben K. Saha, and Nahid Ali. "Differential Decline in Leishmania Membrane Antigen-Specific Immunoglobulin G (IgG), IgM, IgE, and IgG Subclass Antibodies in Indian Kala-Azar Patients after Chemotherapy." Infection and Immunity 67, no. 12 (December 1, 1999): 6663–69. http://dx.doi.org/10.1128/iai.67.12.6663-6669.1999.

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ABSTRACT Pathogenesis in kala-azar is associated with depressed cellular immunity and significant elevation of antileishmanial antibodies. Since these antibodies are present even after cure, analysis of the parasite-specific isotypes and immunoglobulin G (IgG) subclasses in kala-azar patients may shed new light on the immune responses during progression and resolution of infection. Using leishmanial membrane antigenic extracts, we investigated the relative levels of specific IgG, IgM, IgA, IgE, and IgG subclasses in Indian kala-azar patient sera during disease, drug resistance, and cure. Acute-phase sera showed strong stimulation of IgG, followed by IgE and IgM and lastly by IgA antibodies. IgG subclass analysis revealed expression of all of the subclasses, with a predominance of IgG1 during disease. Following sodium stibogluconate (SAG) resistance, the levels of IgG, IgM, IgE, and IgG4 remained constant, while there was a decrease in the titers of IgG2 and IgG3. In contrast, a significant (2.2-fold) increase in IgG1 was observed in these individuals. Cure, in both SAG-responsive and unresponsive patients, correlated with a decline in the levels of IgG, IgM, IgE, and all of the IgG subclasses. The stimulation of IgG1 and the persistence, most importantly, of IgE and IgG4 following drug resistance, along with a decline in IgE, IgG4, and IgG1 with cure, demonstrate the potential of these isotypes as possible markers for monitoring effective treatment in kala-azar.
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10

Fadnis, Madhura P., and Pratibha B. Shamkuwar. "A case of primary immunodeficiency: hyper IgM syndrome." International Journal of Contemporary Pediatrics 6, no. 6 (October 21, 2019): 2700. http://dx.doi.org/10.18203/2349-3291.ijcp20194758.

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Hyper IgM syndrome are group to disorders characterized by elevated serum level of IgM and low or absent serum levels of IgG, IgA and IgE the mechanism of HIGM is immunoglobulin Class-Switch Recombination (CSR) failure and Somatic Hyper Mutation (SHM). This diagnosis should be considered in any patient presenting with hypogammaglobulinemia, with low or absent IgG and IgA and normal or elevated IgM level. In the present case report, this was a 6-year-old male child who had history of recurrent respiratory tract infections who presented with otitis media and persistent fever spikes. Immunoglobulin studies revealed a pattern consistent with hyper IgM.
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11

Anam, Khairul, Farhat Afrin, Dwijadas Banerjee, Netai Pramanik, Subhasis K. Guha, Rama P. Goswami, Pratap N. Gupta, Shiben K. Saha, and Nahid Ali. "Immunoglobulin Subclass Distribution and Diagnostic Value of Leishmania donovani Antigen-Specific Immunoglobulin G3 in Indian Kala-Azar Patients." Clinical Diagnostic Laboratory Immunology 6, no. 2 (March 1, 1999): 231–35. http://dx.doi.org/10.1128/cdli.6.2.231-235.1999.

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ABSTRACT Visceral leishmaniasis, or kala-azar, a fatal tropical disease, remains problematic, as early diagnosis is difficult and treatment often results in drug resistance and relapse. We have developed a sensitive enzyme-linked immunosorbent assay (ELISA), using leishmanial membrane antigenic extracts (LAg) to detect specific antibody responses in 25 untreated Indian visceral leishmaniasis patients. To investigate the pathogenetic significance of isotype markers in kala-azar, relative levels of specific immunoglobulin G (IgG), IgM, IgA, IgE, and IgG subclasses were analyzed under clinically established diseased conditions. Since LAg showed higher sensitivity for specific IgG than lysate, the immunoglobulin isotype responses were evaluated, with LAg as antigen. Compared to 60 controls, which included patients with malaria, tuberculosis, leprosy, and typhoid and healthy subjects, visceral leishmaniasis patients showed significantly higher IgG (100% sensitivity, 85% specificity), IgM (48% sensitivity, 100% specificity), and IgE (44% sensitivity, 98.3% specificity) responses. Low levels of IgA in visceral leishmaniasis patients contrasted with a 13-fold-higher reactivity in sera from patients with leprosy. Among IgG subclasses, IgG1, -3, and -4 responses were significantly higher in visceral leishmaniasis patients than in the controls. IgG2 response, however, was significantly higher (twofold) in leprosy than even visceral leishmaniasis patients. The rank orders for sensitivity (IgG = IgG1 = IgG3 = IgG4 > IgG2 > IgM > IgE > IgA) and specificity (IgM = IgG3 > IgE > IgG4 > IgG2 > IgG > IgG1 > IgA) for LAg-specific antibody responses suggest the potentiality of IgG3 as a diagnostic marker for visceral leishmaniasis.
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12

Zea-Vera, Andres F., Mario Alejandro Chacón, and Beatriz Parra. "Antibody deficiencies with normal IgG in adults with Non-cystic fibrosis bronchiectasis or recurrent pneumonia: Cross-sectional study." Colombia Medica 53, no. 2 (July 11, 2022): e2014832. http://dx.doi.org/10.25100/cm.v53i2.4832.

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Background Inborn errors of immunity, mainly Predominantly Antibody deficiencies with normal IgG levels, are unrecognized in adults with lung diseases such as bronchiectasis or recurrent pneumonia. Objective To determine IgM, IgA, IgG2 subclass deficiencies, and Specific antibody deficiency (anti-pneumococcal polysaccharide antibodies) in adults with non-cystic fibrosis bronchiectasis or recurrent pneumonia. Methods Cross-sectional study. Consecutive patients with non-cystic fibrosis bronchiectasis or recurrent pneumonia were recruited in Cali, Colombia. IgG, IgA, IgM; IgE, IgG2 subclass, and IgG anti-pneumococcal serum levels were measured. Results Among the 110 participants enrolled, Antibody deficiencies with normal serum IgG levels were found in 11(10%) cases. IgA deficiency (3 cases), IgM deficiency (2 cases), and IgG2 deficiency (2 cases) were the most frequent primary immunodeficiencies. In addition, IgG2+IgA deficiency, Ataxia-telangiectasia, Hyper-IgE syndrome and Specific Antibody Deficiency(anti-polysaccharides) were found in one case each. Conclusions Predominantly antibody deficiencies with normal IgG levels are an important etiology of non-cystic fibrosis bronchiectasis and recurrent pneumonia in adults.
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13

Chen, Kang, Giuliana Magri, Emilie K. Grasset, and Andrea Cerutti. "Rethinking mucosal antibody responses: IgM, IgG and IgD join IgA." Nature Reviews Immunology 20, no. 7 (February 3, 2020): 427–41. http://dx.doi.org/10.1038/s41577-019-0261-1.

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14

Efimov, A. S., D. Ch Tajieva, and I. N. Pishel. "Immune mechanisms of development of diabetic nephropathy." Problems of Endocrinology 46, no. 5 (October 15, 2000): 6–10. http://dx.doi.org/10.14341/probl11868.

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Changes in the levels of circulating immunoglobulins and production of autoantibodies to basal membrane of renal glomeruli were studied in patients with insulin-dependent diabetes mellitus (IDDM) at various stages of diabetic nephropathy (DN). The number of patients with positive reaction to autoantibodies to renal basal membrane (R.BM) increases as clinical symptoms of DN augment. The greater part of patients with positive reaction to antibodies have stage 111-IV DN. Measurements of serum immunoglobulin concentrations in patients with DN of different degree showed maximal levels of IgG in initial IDDM (without DN); later IgG level gradually decreases, while IgM level shows a tendency to increase, this increase attaining statistically significant values in patients with pronounced nephropathy. In patients with antibodies to R.BM the ratios of IgG/IgD and IgM/IgD concentrations are elevated, while IgA/IgG and IgA/IgM ratios are lowered; only the IgG/IgD and IgA/IgG ratios differed significantly from the control. 26.8% patients with IDDM had antibodies to basal membrane of renal glomeruli. The number of patients with positive reaction to these antibodies increases with the progress of nephropathy, which can be indicative of the involvement of autoimmune mechanisms in development and progress of DN.
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Stelmach, Iwona, Malgorzata Podsiadłowicz-Borzęcka, Tomasz Grzelewski, Pawel Majak, Wlodzimierz Stelmach, Joanna Jerzyńska, Marta Popławska, and Jaroslaw Dziadek. "Humoral and Cellular Immunity in Children with Mycoplasma pneumoniae Infection: a 1-Year Prospective Study." Clinical Diagnostic Laboratory Immunology 12, no. 10 (October 2005): 1246–50. http://dx.doi.org/10.1128/cdli.12.10.1246-1250.2005.

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ABSTRACT To determine whether children have persistent abnormalities in cellular and humoral immunity development after acute Mycoplasma pneumoniae infection, serum immunoglobulin G (IgG), IgA, IgM, and IgE levels and lymphocyte phenotypes were determined. There were no changes in the levels of IgG, IgM, IgA, or CD4+ or CD19+ lymphocytes that were measured in M. pneumoniae-positive patients after 3 months or after 12 months, but there were increases in these in M. pneumoniae-negative patients. Serum IgE increased in M. pneumoniae-positive patients. We have shown alterations in immunity development after M. pneumoniae infection.
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Jang, Jae-Hyuk, Jiyoung Moon, Eun-Mi Yang, Min Sook Ryu, Youngsoo Lee, Young-Min Ye, and Hae-Sim Park. "Detection of serum IgG autoantibodies to FcεRIα by ELISA in patients with chronic spontaneous urticaria." PLOS ONE 17, no. 8 (August 19, 2022): e0273415. http://dx.doi.org/10.1371/journal.pone.0273415.

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Background Mast cells are a key effector cell in the pathogenesis of chronic spontaneous urticaria (CSU) and activated by circulating FcεRI-specific IgG as well as IgE. This study evaluated the prevalence of circulating autoantibodies to FcεRIα in the sera of CSU patients. Methods Eighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled. To detect circulating autoantibodies (IgG/IgA/IgM) to FcεRIα, ELISA was done using YH35324 (as a solid phase antigen), and its binding specificity was confirmed by the ELISA inhibition test. The antibody levels were presented by the ratio of YH35324-preincubated to mock-preincubated absorbance values. Clinical and autoimmune parameters, including atopy, urticaria activity score (UAS), serum total/free IgE levels, serum antinuclear antibody (ANA) and autologous serum skin test (ASST) results, were assessed. The autoimmune group was defined if CSU patients had positive results to ASST and/or ANA. Results The ratio of serum IgG to FcεRIα was significantly lower in CSU patients than in HCs (P<0.05), while no differences were noted in serum levels of IgG to recombinant FcεRIα or IgA/IgM autoantibodies. The autoimmune CSU group had significantly lower ratios of IgG/IgA (not IgM) autoantibodies to FcεRIα than the nonautoimmune CSU group (P<0.05 for each). No significant associations were found between sex, age, atopy, urticaria duration, UAS, or serum total/free IgE levels according to the presence of IgG/IgA/IgM antibodies. Conclusions This study confirmed the presence of IgG to FcεRIα in the sera of CSU patients, especially those with the autoimmune phenotype.
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Corrado, Alessia, Richard P. Ramonell, Matthew C. Woodruff, Christopher Tipton, Sarah Wise, Joshua Levy, John DelGaudio, et al. "Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa." Mucosal Immunology 14, no. 5 (May 28, 2021): 1144–59. http://dx.doi.org/10.1038/s41385-021-00410-w.

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AbstractIncreased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC). Using VH next generation sequencing, we identified an extrafollicular (EF) mucosal IgD+ naïve-like intermediate B cell population with high connectivity to the mucosal IgE ASC. Mucosal IgD+ B cells, express germline epsilon transcripts and predominantly co-express IgM. However, a small but significant fraction co-express IgG or IgA instead which also show connectivity to ASC IgE. Phenotypically, NP IgD+ B cells display an activated profile and molecular evidence of BCR engagement. Transcriptionally, mucosal IgD+ B cells reveal an intermediate profile between naïve B cells and ASC. Single cell IgE ASC analysis demonstrates lower mutational frequencies relative to IgG, IgA, and IgD ASC consistent with IgE ASC derivation from mucosal IgD+ B cell with low mutational load. In conclusion, we describe a novel mechanism of GC-independent, extrafollicular IgE ASC formation at the nasal mucosa whereby activated IgD+ naïve B cells locally undergo direct and indirect (through IgG and IgA), IgE class switch.
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18

Kouvalainen, K., and I. Moilanen. "Intrapair Similarity of Immunoglobulin Levels in Twins." Acta geneticae medicae et gemellologiae: twin research 36, no. 4 (October 1987): 509–15. http://dx.doi.org/10.1017/s0001566000006887.

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AbstractLevels of immunoglobulins IgG, IgA, IgM and IgE were determined in 8 MZ and 14 DZ twin pairs at the ages of 6-11 years, 12-17 years and 15-20 years. Intrapair similarity in immunoglobulin levels was found to be higher in the MZ than in the DZ twins, especially in the case of immunoglobulins IgA and IgM.
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19

Ginkel, Frederik W. van, Sharon M. Wahl, John F. Kearney, Mi-Na Kweon, Kohtaro Fujihashi, Peter D. Burrows, Hiroshi Kiyono, and Jerry R. McGhee. "Partial IgA-Deficiency with Increased Th2-Type Cytokines in TGF-β1 Knockout Mice." Journal of Immunology 163, no. 4 (August 15, 1999): 1951–57. http://dx.doi.org/10.4049/jimmunol.163.4.1951.

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Abstract Though it has been shown that TGF-β1 directs B cells to switch to IgA in vitro, no studies have assessed TGF-β1 effects on mucosal vs systemic immunity in vivo. When the B cell functions of TGF-β1 gene-disrupted (TGF-β1−/−) mice were analyzed, significantly decreased IgA levels and increased IgG and IgM levels in serum and external secretions were observed. Further, analysis of Ab forming cells (AFC) isolated from both mucosal and systemic lymphoid tissue showed elevated IgM, IgG, and IgE, with decreased IgA AFC. A lack of IgA-committed B cells was seen in TGF-β1−/− mice, especially in the gastrointestinal (GI) tract. Splenic T cells triggered via the TCR expressed elevated Th2-type cytokines and, consistent with this observation, a 31-fold increase in serum IgE was seen in TGF-β1−/− mice. Thus, uncontrolled B cell responses, which include elevated IgE levels, a lack of antiinflammatory IgA, and an excess of complement-binding IgG and IgM Abs, will promote inflammation at mucosal surfaces in TGF-β1−/− mice and likely contribute to pulmonary and GI tract lesions, ultimately leading to the early death of these mice.
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Mathur, A., and R. G. Lynch. "Increased T gamma and T mu cells in BALB/c mice with IgG and IgM plasmacytomas and hybridomas." Journal of Immunology 136, no. 2 (January 15, 1986): 521–25. http://dx.doi.org/10.4049/jimmunol.136.2.521.

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Abstract The results of previous studies in our laboratory have shown that mice bearing plasmacytomas and hybridomas that secrete IgA or IgE are accompanied by increased frequencies of Lyt-1-2+ T lymphocytes bearing Fc receptors (FcR) for IgA (T alpha) or IgE (T epsilon), respectively. The present study was undertaken to examine whether IgG- or IgM-secreting tumors influenced the frequency of T lymphocytes that express FcR for IgG or IgM. We studied mice bearing IgG- and IgM-secreting plasmacytomas and hybridomas. BALB/c mice injected subcutaneously with the IgG-secreting hybridoma HDP1 (gamma 1 kappa, anti-TNP) were sequentially examined for the frequencies and Lyt phenotypes of splenic lymphocytes bearing FcR for IgG (T gamma), IgM (T mu), and IgA (T alpha). A threefold increase in the frequency of T gamma lymphocytes that were Lyt-1-2+, L3T4- was seen. The frequencies of T mu and T alpha lymphocytes in these mice were not significantly altered. Similarly, mice injected subcutaneously with the IgM-secreting plasmacytoma MOPC 104E (mu lambda, anti-dextran) or the IgM-secreting hybridoma C1D1 (mu kappa, anti-ox RBC) were examined sequentially for the frequencies of T gamma, T mu, and T alpha lymphocytes. Mice with established IgM subcutaneous tumors showed a twofold increase in splenic, nylon wool-nonadherent T mu lymphocytes. This was associated with a relative increase in Lyt-2+ splenic T lymphocytes and a relative decrease in Lyt-1+ splenic T lymphocytes. No changes were observed in the frequencies of either T gamma or T alpha lymphocytes. These studies extend to IgG and IgM the observation that plasmacytomas and hybridomas secreting immunoglobulins of a specific isotype cause an expansion of T lymphocytes bearing FcR specific for the corresponding isotype. The expansion of FcR+ Lyt-1-2+ T lymphocytes likely represents an exaggerated, but otherwise normal, immunoregulatory response of the host. These cells may be an important element in the regulation of isotype expression.
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Zhang, X. H., C. Werner-Favre, H. Y. Tang, N. Brouwers, J. Y. Bonnefoy, and R. H. Zubler. "IL-4-dependent IgE switch in membrane IgA-positive human B cells." Journal of Immunology 147, no. 9 (November 1, 1991): 3001–4. http://dx.doi.org/10.4049/jimmunol.147.9.3001.

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Abstract IgE responses by human B cells, separated according to membrane Ig classes, were analyzed in a clonal assay using EL-4 thymoma cells as helper cells, T cell supernatant, and rIL-4. In cultures seeded by means of the autoclone apparatus of the FACS, IgE responses were generated frequently by either IgM (mu+/gamma-alpha-) or IgA (alpha +/mu-)-positive B cells (16 and 14% of the Ig producing wells, respectively), but rarely by IgG (gamma +/mu-)-positive B cells (1.3% of Ig producing wells). The total amounts of Ig secreted by IgM-, IgG-, or IgA-positive cells and the total proportions of responding autoclone wells (23-27%) were comparable. All IgE secretion was IL-4 dependent. When the Ig secretion patterns from alpha +/mu- vs alpha +/mu-epsilon- B cells were compared, most autoclone wells from both types of cells produced IgA only, and similar proportions of IgA producing wells (6.2 and 6.0%) also secreted IgE. In addition, IgE restricted responses occurred 6 times more frequently with alpha +/mu- than with alpha +/mu-epsilon- cells, which suggests that membrane IgA+E double-positive, IgE committed B cells occur in vivo. The isotype pattern generated by alpha +/mu-epsilon- B cells cannot be explained by a chance assortment of separate IgA and IgE precursors or by cytophilic antibody. Thus, IL-4 dependent switch to IgE occurred frequently in IgM- or IgA-positive, but rarely among total IgG-positive, B cells. This could be relevant to IgE production in mucosal tissues rich in IgA expressing B cells.
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Patel, J. Y., and D. P. Huston. "A novel immunoglobulin phenotype: Profound deficiency of IgM, IgD, IgA, and IgE with normal IgG." Journal of Allergy and Clinical Immunology 115, no. 2 (February 2005): S160. http://dx.doi.org/10.1016/j.jaci.2004.12.653.

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23

Manzhos, M. V., E. S. Fedenko, M. A. Myagkova, B. A. Molotilov, S. A. Shkadov, S. N. Petrochenko, R. Yu Kiseleva, et al. "Influence of sublingual allergen-specific immunotherapy on dynamics of immunological parameters in patients with pollinosis." Russian Journal of Allergy 6, no. 1 (March 15, 2009): 39–44. http://dx.doi.org/10.36691/rja1033.

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Background. To study the influence of sublingual allergen-specific immunotherapy (slASIT) on dynamics of immunologic parameters in patients with pollinosis. Materials and methods. 40 healthy persons and 25 pollinosis patients received slASIT course with mixt of autumn grasses allergen. IgA, IgM, IgG, IgE antibodies, slgA, albumin in saliva and IgA, IgM, IgG, IgE antibodies, total IgE, IFN-γ, IL-4 in serum were investigated. Results. Patients with pollinosis have infringements of both local and general immunity. SlASIT changes a profile of cytokines aside Th-1, stimulates formation of the secretory allergen-specific antibodies, reduces IgE antibodies in saliva. Conclusion. SlASIT is a highly effective method of allergic diseases treatment and it induces B-cellular and T-cellular tolerance.
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Sandor, M., T. Gajewski, J. Thorson, J. D. Kemp, F. W. Fitch, and R. G. Lynch. "CD4+ murine T cell clones that express high levels of immunoglobulin binding belong to the interleukin 4-producing T helper cell type 2 subset." Journal of Experimental Medicine 171, no. 6 (June 1, 1990): 2171–76. http://dx.doi.org/10.1084/jem.171.6.2171.

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A panel of 20 murine CD4+ clones was examined for the presence of surface membrane receptors for IgA, IgM, IgD, IgE, and IgG. High level expression of multiple Fc receptors (FcRs) was found on all Th2 clones. FcR expression was low or undetected on the Th1 clones. The preferential expression of FcR on activated Th2 cells suggests potential mechanisms for immunoregulatory interactions with B cells.
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Martin, Valentina, Miriam Arcavi, Graciela Santillan, Maria Regina R. Amendoeira, Elizabeth De Souza Neves, Gloria Griemberg, Eduardo Guarnera, Juan C. Garberi, and Sergio O. Angel. "Detection of Human Toxoplasma-Specific Immunoglobulins A, M, and G with a Recombinant Toxoplasma gondii Rop2 Protein." Clinical Diagnostic Laboratory Immunology 5, no. 5 (September 1, 1998): 627–31. http://dx.doi.org/10.1128/cdli.5.5.627-631.1998.

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ABSTRACT The Toxoplasma gondii rhoptry protein Rop2 was expressed in Escherichia coli as a fusion protein containing 44 kDa of the 55-kDa mature Rop2, supplied with six histidyl residues at the N-terminal end (Rop2196–561). Humoral response during Toxoplasma infection of humans was analyzed by immunoglobulin G (IgG), IgA, and IgM enzyme-linked immunosorbent assay with Rop2196–561 as the antigen substrate. The analyzed sera were divided according to T. gondii-specific serological tests (IgG, IgA, or IgM indirect immunofluorescence and IgA or IgM immunosorbent agglutination assay) as group A (IgG+ IgA− IgM−;n = 35), group B (IgG+ IgA+IgM+; n = 21), group C (IgG+IgA+ IgM−; n = 5), and group D (IgG+ IgA− IgM+;n = 16). Twenty-six T. gondii-seronegative sera from individuals with other infections were also included (group E). Anti-Rop2 IgG antibodies were detected in 82.8% of group A sera and in 97.6% of the sera with acute-phase marker immunoglobulins (groups B, C, and D). The percentage of IgA antibody reactivity against Rop2196–561 was 17.1% in group A, 50% in group D, and 80.8% in groups B and C. The percentage of IgM antibody reactivity was 0% in groups A and C and 62% in groups B and D. Sera from group E failed to show IgA, IgM, or IgG antibody reactivity. Since T. gondii Rop2 elicits a strong humoral response from an early stage of infection, it is suggested that recombinant Rop2196–561 would be suitable for use in diagnostic systems, in combination with other T. gondii antigens, to detect specific IgG, IgA, and IgM antibodies.
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Araj, G. F., A. R. Lulu, M. I. Khateeb, and M. Haj. "Specific IgE response in patients with brucellosis." Epidemiology and Infection 105, no. 3 (December 1990): 571–77. http://dx.doi.org/10.1017/s0950268800048202.

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SUMMARYIn the search to find discriminative serological markers to differentiate between patients with acute brucellosis and those with chronic brucellosis, an enzyme-linked immunosorbent assay (ELISA) was used to determine and compare the brucella-specific IgE response in 80 sera from patients with acute brucellosis, 37 sera from patients with chronic brucellosis, 26 sera from patients with positive blood cultures for bacteria other than brucella and 51 sera from healthy controls. The IgE findings were compared to brucella-specific IgG, IgM, IgA and IgG1–4demonstrated by ELISA, and to microagglutination test (MAT) results. Elevated (positive) antibrucella IgE titres were detected in 89 and 81 % of sera from patients with acute and chronic brucellosis respectively. The predominant antibodies found in patients with acute brucellosis were of the IgG, IgM, IgA, IgE, IgG1and IgG3types while in chronic brucellosis IgG, IgA, IgE and IgG4were found. Although IgE can be detected in patients with brucellosis, it does not discriminate between the acute and chronic stages of the disease.
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Cheldieva, F., T. Reshetnyak, M. Cherkasova, N. Seredavkina, and A. Lila. "POS0712 “EXTRA”- CRITERIA ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 605.2–606. http://dx.doi.org/10.1136/annrheumdis-2021-eular.818.

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Background:The study of antiphospholipid antibodies (aPL), not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood.Objectives:To determine the frequency of detection of IgA-aCL and IgA-aβ2GP1 and IgG antibodies to β2GP1 domain 1 (IgG-aβ2GP1-D1) in patients with APS with and without SLE.Methods:ELISA and chemiluminescence assays (CMA) were used to test 63 sera of patients: 22 (35%) with primary APS (pAPS) and 41 (65%) patients with APS and with SLE (secondary APS (sAPS)), with mean age 38,0 [33,0 – 43,0] years and disease duration 4,0 [0,1 – 9,9]. Both methods were used to test of IgG/IgM-aCL and IgG/IgM-aβ2GP1. CMA was used for research IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GPI and IgG-aβ2GP1-D1. Of them 49 (78%) (18 – with pAPS; 31 – with sAPS) displayed major thrombotic events and 18 of 22 pregnant women had pregnancy morbidity in past history. Lupus anticoagulant (LA) positivity was in 9 out of 12 patients who had it determined. LA was not investigated due to anticoagulant therapy in the remaining 52 patients.Results:IgG/IgM-aCL and IgG/IgM-aß2GP1 were recorded in 44/18 and 50/17 patients by ELISA and in 55/19 and 59/16 by CMA, respectively.IgA-aCL positivity was found in 35 (56%) of 63 patients. Thirty IgA-positive patients were positive for IgG-aCL by ELISA: 22 – IgG-aCL – highly positive, 6 – medium positive and 2 – low positive patients. IgM-aCL by ELISA was detected in 13 (37%) of 35 IgA-aCL positive patients: 11 – highly positive, 1 – medium positive and 1 – low positive. IgA-aCL was combined with IgG-aCL in 34 patients and with IgM-aCL in 16 patients in the CMA. IgG-aß2GP1 in ELISA was detected in 32 patients with IgA-aCL (24 –highly positive, 5 – medium positive and 3 – low positive) and in 34 – in CMA. IgM-aß2GP1 was combined with IgA-aß2GP1 with the same frequency in both methods (in 13 patients).IgA-aß2GP1 was detected in 30 (48%) of 63 patients. They were combined with both IgG-aCL and IgG-aß2GP1 in all cases in both methods. IgM-aCL and IgM-aß2GP1 were detected in 14 and 11 of 30 patients with IgA-aß2GP1, respectively. The combination of IgA-aß2GP1 with IgG-aCL by ELISA was in 27 (in most cases highly positive – 20) and with IgM-aCL – in 10 (highly positive - 8). IgG-aß2GP1 was detected in 28 patients with IgA-aß2GP1 (high positive – 21) and in 11 patients with IgM-aß2GP1 (high positive –7).IgG-aß2GP1-D1 was revealed in 48 (76%) patients. It was combined with IgG-aCL – in 38, with IgM-aCL – in 15 patients by the ELISA. The combination of IgG-aß2GP1-D1 by CMA was as follows: with IgG-aCL – in 46, with IgM-aCL – in 17, and with IgA-aCL – in 33 patients. In most cases, IgG-aß2gp1-D1 was combined with highly positive aCL levels. IgG-aß2GP1-D1 positivity was associated with IgG-aß2GP1 positivity in 42 – by ELISA and 47 – by CMA, IgМ-aβ2GP1 – in 13 and 14 patients by ELISA and CMA, respectively, and IgA-aß2GP1 – in 29. Isolated IgG-aß2GP1-D1 positivity was not observed.Conclusion:The frequency of IgA-aCL detection was 56% (35 patients out of 63), IgA-aβ2GP1 – 48% (30 patients out of 63), IgG-aβ2GP1-D1 – 76% (48 patients out of 63). There was not isolated positivity of this “extra” criterial antibodies. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with highly positivity of IgG/IgM-aCL and IgG/IgM- aβ2GP1.Disclosure of Interests:None declared
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Cheldieva, F. A., T. M. Reshetnyak, M. V. Cherkasova, and A. M. Lila. "Extra criterial antiphospholipid antibodies in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data)." Modern Rheumatology Journal 15, no. 5 (October 20, 2021): 18–25. http://dx.doi.org/10.14412/1996-7012-2021-5-18-25.

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The role of antiphospholipid antibodies (aPL), which are not included in the classification criteria, in antiphospholipid syndrome (APS) andsystemic lupus erythematosus (SLE) is not well understood.Objective: to determine the frequency of detection of IgG antibodies to domain 1 of β2-glycoprotein 1 (IgG-aβ2GP1-D1), IgA antibodiesto cardiolipin (aCL) and IgA antibodies to β2-glycoprotein 1 (IgA-a β2GP1) in patients with primary APS and APS in combination withSLE.Patients and methods. The study included 63 patients in whom IgG/IgM-aCL and IgG/IgM-aβ2GP1 were detected by enzyme-linkedimmunosorbent assay (ELISA) and IgG/IgM/IgA-aCL, IgG/IgM/IgA-aβ2GP1 and IgG-aβ2GP1-D1 by chemiluminescence analysis (CLA).Results and discussion. The detection rate of IgG-aβ2GP1-D1 was 76%, IgA-aCL – 56%, IgA-aβ2GP1 – 48%. Isolated positivity for IgA-aCL,IgA-aβ2GP1, IgG-aβ2GP1-D1 was not observed. The presence of IgA-aCL, IgA-aβ2GP1, IgG-aβ2GP1-D1 was associated with high positivity forIgG/IgM-aCL and IgG/IgM-aβ2GP1. There was a statistically significant relationship between IgA-aCL/IgA-aβ2GP1 and the standard aPLprofile, as well as IgG-aβ2GP1-D1, IgG-aCL and IgG-aβ2GP1.Conclusion. A high detection rate of IgG-aβ2GP1-D1, IgA-aCL, IgA-aβ2GP1 was found in patients with APS. A statistically significant relationshipwas found between IgA-aCL/IgA-aβ2GP1 and the standard aPL profile, as well as IgG-aβ2GP1-D1 with IgG-aCL and IgG-aβ2GP1.
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Kindler, V., and R. H. Zubler. "Memory, but not naive, peripheral blood B lymphocytes differentiate into Ig-secreting cells after CD40 ligation and costimulation with IL-4 and the differentiation factors IL-2, IL-10, and IL-3." Journal of Immunology 159, no. 5 (September 1, 1997): 2085–90. http://dx.doi.org/10.4049/jimmunol.159.5.2085.

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Abstract The ligation of CD40 on B lymphocytes by CD40 ligand, transiently expressed on activated Th cells, provides a key activation signal required for the germinal center B cell response. In vitro, human B cell activation has been investigated extensively by coculturing tonsillar B cells with CD32-transfected fibroblasts coated with anti-CD40 Abs, in the presence of cytokines (the CD40 system). When tonsillar IgD+ B cells are cultured in the CD40 system with IL-4, cells proliferate and switch to IgG, but they display a block of differentiation illustrated by the persistence of IgD expression on cycling B cells. In this study, we analyzed the responses of peripheral blood B lymphocyte fractions, which may contain fewer in vivo activated cells than those from tonsils. While the differentiation block was confirmed with peripheral naive B cells cultured in the CD40 system with IL-4, it was also observed with the combination of IL-2, IL-10, and IL-3 alone or together with IL-4 (persistence of &gt;90% IgD+ cells, including 24-60% IgD+, IgG+ cells, and &lt;6% IgD+, IgA+ cells after 8 days). IgD+, IgG-, and IgA- (naive) B cells secreted 70-fold less Ig than IgG+, IgA+ (memory) B cells in response to anti-CD40 plus IL-2, IL-10, and IL-3. IgG-, IgA- B cells, or IgD-, IgM+, which should include IgM+ memory cells, strongly secreted IgM, but no IgG. In conclusion, only memory B cells secreted Ig; like memory T cells, their activation requirements to differentiate into effector cells seem less stringent than those of the naive cells.
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Knight, K. L., and R. S. Becker. "Isolation of genes encoding bovine IgM, IgG, IgA and IgE chains." Veterinary Immunology and Immunopathology 17, no. 1-4 (December 1987): 17–24. http://dx.doi.org/10.1016/0165-2427(87)90123-1.

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31

Jost, Sheridan A., Lin-Chiang Tseng, Loderick A. Matthews, Rebecca Vasquez, Song Zhang, Kim B. Yancey, and Benjamin F. Chong. "IgG, IgM, and IgA Antinuclear Antibodies in Discoid and Systemic Lupus Erythematosus Patients." Scientific World Journal 2014 (2014): 1–7. http://dx.doi.org/10.1155/2014/171028.

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IgG antinuclear antibodies (ANAs) are elevated in patients with systemic lupus erythematosus (SLE) compared with patients with discoid lupus erythematosus (DLE). To provide an expanded immunologic view of circulating ANAs in lupus patients, we compared the expressions of IgG, IgM, and IgA ANAs in DLE and SLE patients. In this cross-sectional study, sera from age-, gender-, and ethnic-matched SLEN=35, DLEN=23, and normal patientsN=22were tested for IgG, IgM, and IgA ANAs using enzyme-linked immunosorbent assays (ELISAs) and indirect immunofluorescence (IIF) with monkey esophagus as substrate. ELISAs showed elevated levels of IgG ANA, IgM ANA, and IgG/IgM ANA ratios in SLE patients compared with DLE and normal patients. IgA ANA expression was higher in SLE and DLE patients versus normal patients. IIF studies showed higher percentages of patients positive for IgG, IgM, and IgA ANAs in the SLE group. Higher IgG/IgM ANA ratios in SLE than DLE show enhanced class-switching and a more sustained humoral response in SLE. They also suggest a potential connection of IgM ANAs with disease containment.
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Hjelt, Karsten, Christian Hjort Sorensen, Ole H. Nielsen, and Peter A. Krasilnikoff. "Concentrations of IgA, Secretory IgA, IgM, Secretory IgM, IgD, and IgG in the Upper Jejunum of Children Without Gastrointestinal Disorders." Journal of Pediatric Gastroenterology and Nutrition 7, no. 6 (November 1988): 867–71. http://dx.doi.org/10.1097/00005176-198811000-00013.

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Postan, Miriam, Luz Quebrada Palacio, Yolanda Hernandez-Vasquez, and Esteban Fernandez. "Chronic infection with trypanosoma cruzi alters the phenotypic profile of circulating memory B cells in humans (MPF2P.812)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 67.11. http://dx.doi.org/10.4049/jimmunol.192.supp.67.11.

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Abstract Trypanosoma cruzi was shown to induce the loss of parasite-specific IgG-producing B cells during the acute infection of mice, which was proposed to hamper B cell responses and favor parasite replication and chronicity (Zuñiga et al. 2002). Herein, we measured the levels of circulating memory and MZ-like B cells in 12 individuals chronically infected with T. cruzi and 9 healthy controls based on the expression of CD19, IgM IgD, IgG, and CD27. T. cruzi-infected individuals had significantly lower percentages of IgM+IgD-CD27+ (IgM-only), IgM-IgD-CD27+ (isotype-switched) and IgG+IgD-CD27+ memory B cells compared to controls (p&lt;0.05). Also, the percentage of IgM+IgD+CD27+ (MZ-like) B cells was reduced in infected individuals while the proportion of IgG+IgD-CD27- memory B cells was increased (p&lt;0.05). The levels of memory B cells were further analyzed according to ECG findings in infected individuals (asymptomatic [ASY] and chronic Chagas heart disease [CHD]). IgG+IgD-CD27+, IgM+IgD-CD27+ and IgM-IgD-CD27+ B cells were significantly reduced in the ASY group compared to controls (p&lt;0.05); CHD individuals had decreased levels of IgM-IgD-CD27+ and IgM+IgD-CD27+ B cells (p&lt;0.05). Altogether, our data indicate that chronic exposure to T. cruzi modulates the phenotypic profile of the peripheral blood CD19+ B cell compartment in humans, and that some of the defects develop early in the infection, prior the onset of heart symptoms. Supported by Argentinian MINCYT/FONCYT PICT 2010-2148
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Mayer, L., D. N. Posnett, and H. G. Kunkel. "Human malignant T cells capable of inducing an immunoglobulin class switch." Journal of Experimental Medicine 161, no. 1 (January 1, 1985): 134–44. http://dx.doi.org/10.1084/jem.161.1.134.

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Evidence is presented for the existence of a "switch" T cell derived from a patient with mycosis fungoides/Sezary's syndrome. The serum immunoglobulin profile in this patient revealed high IgG and IgA but no detectable IgM. Peripheral blood mononuclear cells from this patient secreted only IgG and IgA in the presence of pokeweed mitogen. T cells (Trac) co-cultured with normal allogeneic non-T cells and pokeweed mitogen resulted in only IgG and IgA PFC, with little or no IgM secretion. There was no evidence of active suppression of IgM. Rather, these T cells appeared to induce an Ig class switch from IgM to IgG and IgA, when co-cultured with mu+ tonsillar B cells. Further evidence was obtained using mononuclear cells derived from a patient with immunodeficiency and hyper-IgM, a syndrome characterized by a lack of IgG and IgA secretion. The addition of Trac cells to either peripheral blood mononuclear cells or non-T cells from a patient with hyper-IgM syndrome resulted in new secretion of IgG, with a concomitant decrease in IgM secretion, whereas control T cells were not effective in inducing secretion of any isotype other than IgM. Isolated Tac+ T cells from Trac appear to be responsible for this effect.
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35

Mellert, Tuesday K., Marilyn L. Getchell, Larry Sparks, and Thomas V. Getchell. "Characterization of the Immune Barrier in Human Olfactory Mucosa." Otolaryngology–Head and Neck Surgery 106, no. 2 (August 1992): 181–88. http://dx.doi.org/10.1177/019459989210600221.

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Immunologic defense factors in the human olfactory mucosa were localized immunohistochemically. Olfactory epithelium was identified with an antiserum to olfactory marker protein, specific for olfactory receptor neurons. Constituents of the secretory immune system, including IgA, IgM, secretory component, and J chain, were localized in the acinar and duct cells of Bowman's glands and in the mucociliary complex. In addition, B lymphocytes in the lamina propria near Bowman's glands displayed immunoreactivity for IgA, IgM, and J chain. Immunostaining also localized other humoral factors. Immunoreactivity for IgG was present throughout the stroma and in B lymphocytes in the lamina propria. Antibody to IgD stained numerous B lymphocytes clustered below the basement membrane. Antibody to IgE stained similarly distributed cells; toluidine blue staining demonstrated that many were mast cells. In addition, antibodies to IgD and IgE stained occasional intraepithelial B lymphocytes or mast cells. Two antimicrobial proteins, lactoferrin and lysozyme, were localized in Bowman's glands and the mucociliary complex. Thus, the human olfactory mucosa, which provides a direct neural route for pathogens to the brain, is a site for synthesis and secretion of immune and other defense factors.
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Roa, Sergio, Maria Isidoro-Garcia, Ignacio Davila, Elena Laffond, Felix Lorente, and Rogelio Gonzalez-Sarmiento. "Molecular Analysis of Activation-Induced Cytidine Deaminase Gene in Immunoglobulin-E Deficient Patients." Clinical and Developmental Immunology 2008 (2008): 1–6. http://dx.doi.org/10.1155/2008/146715.

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Understanding how class switch recombination (CSR) is regulated to produce immunoglobulin E (IgE) has become fundamental because of the dramatic increase in the prevalence of IgE-mediated hypersensitivity reactions. CSR requires the induction of the enzyme AICDA in B cells. Mutations in AICDA have been linked to Hyper-IgM syndrome (HIGM2), which shows absence of switching to IgE as well as to IgG and IgA. Although isolated IgE deficiency is a rare entity, here we show some individuals with normal serum IgM, IgG, and IgA levels that had undetectable total serum IgE levels. We have analyzed theAICDAgene in these individuals to determine if there are mutations in AICDA that could lead to selective IgE deficiency. Conformational sensitive gel electrophoresis (CSGE) and sequencing analysis ofAICDAcoding sequences demonstrated sequence heterogeneity due to 5923A/G and 7888C/T polymorphisms, but did not reveal any novel mutation that might explain the selective IgE deficit.
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de Sousa, Graziele Fonseca, Thuany da Silva Nogueira, Lana Soares de Sales, Fernanda Ferreira Maissner, Odara Araújo de Oliveira, Hellade Lopes Rangel, Daniele das Graças dos Santos, et al. "The long-term dynamics of serum antibodies against SARS-CoV-2." PeerJ 10 (December 15, 2022): e14547. http://dx.doi.org/10.7717/peerj.14547.

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Objective To analyze the long-term dynamics of antibodies against SARS-CoV-2 and understand the impact of age, gender, and viral load on patients’ immunological response. Methods Serum samples were obtained from 231 COVID-19 positive patients from Macaé, in Rio de Janeiro state, in Brazil, from June 2020 until January 2021. The production of IgA, IgM, IgG, and IgE against S glycoprotein was analyzed using the S-UFRJ assay, taking into account the age, gender, and viral load. Results Analysis of antibody production over 7 months revealed that IgA positivity gradually decreased after the first month. Additionally, the highest percentage of IgM positivity occurred in the first month (97% of patients), and declined after this period, while IgG positivity remained homogeneous for all 7 months. The same analysis for IgE revealed that almost all samples were negative. The comparison of antibody production between genders showed no significant difference. Regarding the age factor and antibody production, patients aged ≥60 years produced almost twice more IgA than younger ones (17–39 years old). Finally, a relationship between viral load and antibody production was observed only for older patients. Conclusions Our work provides an overview of long-term production of antibodies against SARS-CoV-2, suggesting prolonged production of IgA and IgM antibodies for 3 months and continued IgG production for over 7 months. In addition, it identified a correlation between viral load and IgM titers in the older group and, finally, different IgA production between the age groups.
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Nawata, Y., T. Koike, H. Hosokawa, H. Tomioka, and S. Yoshida. "Anti-IgE autoantibody in patients with atopic dermatitis." Journal of Immunology 135, no. 1 (July 1, 1985): 478–82. http://dx.doi.org/10.4049/jimmunol.135.1.478.

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Abstract The anti-IgE autoantibody in the IgG class was detected in 39/45 (86.7%) patients with atopic dermatitis by using a newly established solid-phase enzyme immunoassay. The epsilon-chain specificity of the anti-IgE autoantibody was confirmed by competitive inhibition by using human IgG, IgA, IgM, IgD, IgE, and heat-denatured IgE protein. Significant correlations were observed between the levels of the anti-IgE autoantibody and the serum IgE. Gel filtration studies indicated that the anti-IgE autoantibody in sera from atopic dermatitis was mainly present in the form of an immune complex with self IgE. The role of the IgE-anti-IgE immune complex and the role of the anti-IgE autoantibody in the modulation of the IgE-mediated immune system in atopic dermatitis are discussed.
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Nielsen, Sandra C. A., Krishna M. Roskin, Katherine J. L. Jackson, Shilpa A. Joshi, Parastu Nejad, Ji-Yeun Lee, Lisa E. Wagar, et al. "Shaping of infant B cell receptor repertoires by environmental factors and infectious disease." Science Translational Medicine 11, no. 481 (February 27, 2019): eaat2004. http://dx.doi.org/10.1126/scitranslmed.aat2004.

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Antigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)–mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure. IgE mutation frequencies are primarily increased in children with impaired skin barrier conditions such as eczema, suggesting that IgE affinity maturation could provide a mechanistic link between epithelial barrier failure and allergy development.
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Prince, Harry E., and Mary Lapé-Nixon. "Evaluation of a West Nile Virus Immunoglobulin A Capture Enzyme-Linked Immunosorbent Assay." Clinical Diagnostic Laboratory Immunology 12, no. 1 (January 2005): 231–33. http://dx.doi.org/10.1128/cdli.12.1.231-233.2005.

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ABSTRACT An in-house-developed enzyme-linked immunosorbent assay detected West Nile virus (WNV) immunoglobulin A (IgA) in 65 of 68 sera from WNV-infected patients; 40 of 63 WNV IgM-positive, IgG-negative serum or plasma specimens; 65 of 67 WNV IgM-positive, IgG-positive specimens; 0 of 70 WNV IgM-negative, IgG-negative specimens; and 0 of 64 archived blood donation sera. WNV IgA is thus highly prevalent among WNV-infected patients and typically appears after WNV IgM but before WNV IgG.
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Miletic, V. D., C. G. Hester, and M. M. Frank. "Regulation of complement activity by immunoglobulin. I. Effect of immunoglobulin isotype on C4 uptake on antibody-sensitized sheep erythrocytes and solid phase immune complexes." Journal of Immunology 156, no. 2 (January 15, 1996): 749–57. http://dx.doi.org/10.4049/jimmunol.156.2.749.

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Abstract Intravenous Ig, composed principally of IgG, prevents complement attack by inhibiting C3 and C4 uptake onto target cells and tissues. Using two different models, Ab-sensitized SRBC and BSA-anti BSA solid phase immune complexes, we have examined the complement inhibitory capacity of three Ig classes (IgG, IgM, IgA) focussing on inhibition of C4 uptake. It was found that on both a weight and molar basis, monomeric serum IgA and IgM were far more active than IgG (weight efficiency ratios were 1.0, 20.8, and 236.3, and molar efficiency ratios 1.0, 24.0, and 1382.9 for polyclonal IgG, IgA1, and IgM, respectively). Monoclonal IgM were less active than polyclonal IgM (50% inhibition was achieved in SRBC model by 0.022, 0.30, 1.6, and 1.6 mg/ml of polyclonal IgM and monoclonal IgM from patients Lew, Will, and Pri). Secretory IgA was less active than serum IgA1 and similar in inhibitory activity to IgG (weight and molar efficiency ratios 1.5 and 0.6 compared with IgG). All tested preparations were less active in the solid phase immune complex model than in the sensitized cell model. A mixture of Igs of different isotypes was somewhat more active than any isotype alone. These results suggest that polyclonal serum IgA and IgM can also be considered for active therapy in diseases accompanied by the activation of classical complement pathway.
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42

Tešija Kuna, Andrea, Marijana Miler, Mario Štefanović, Ivan Šamija, Josipa Periša, Sandra Šupraha Goreta, Sanja Tadinac, et al. "Comparison of diagnostic accuracy for eight SARS-CoV-2 serological assays." Biochemia medica 31, no. 1 (February 15, 2021): 121–33. http://dx.doi.org/10.11613/bm.2021.010708.

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Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serological tests have been suggested as an additional diagnostic tool in highly suspected cases with a negative molecular test and determination of seroprevalence in population. We compared the diagnostic performance of eight commercial serological assays for IgA, IgM, and IgG antibodies to the SARS-CoV-2 virus. Materials and methods: The comparison study was performed on a total of 76 serum samples: 30 SARS-CoV-2 polymerase chain reaction (PCR)- negative and 46 SARS-CoV-2 PCR-positive patients with asymptomatic to severe disease and symptoms duration from 3-30 days. The study included: three rapid lateral flow immunochromatographic assays (LFIC), two enzyme-linked immunosorbent assays (ELISA), and three chemiluminescence immunoassays (CLIA). Results: Agreement between IgM assays were minimal to moderate (kappa 0.26 to 0.63) and for IgG moderate to excellent (kappa 0.72 to 0.92). Sensitivities improved with > 10 days of symptoms and were: 30% to 89% for IgM; 89% to 100% for IgG; 96% for IgA; 100% for IgA/IgM combination; 96% for total antibodies. Overall specificities were: 90% to 100% for IgM; 85% to 100% for IgG; 90% for IgA; 70% for IgA/IgM combination; 100% for total antibodies. Diagnostic accuracy for IgG ELISA and CIA assays were excellent (AUC ≥ 0.90), without significant difference. IgA showed significantly better diagnostic accuracy than IgM (P < 0.001). Conclusion: There is high variability between IgM assays independently of the assay format, while IgG assays showed moderate to perfect agreement. The appropriate time for testing is crucial for the proper immunity investigation.
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MARTINS, Rosana, Sílvio MARQUES, Marino ALVES, Denise FECCHIO, and Marcello F. de FRANCO. "Serological follow-up of patients with paracoccidioidomycosis treated with itraconazole using Dot-blot, ELISA and Western-blot." Revista do Instituto de Medicina Tropical de São Paulo 39, no. 5 (September 1997): 261–70. http://dx.doi.org/10.1590/s0036-46651997000500004.

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Twenty-seven mycologically proven cases of paracoccidioidomycosis (PCM) were treated with itraconazole (100-200 mg/day in month 1 and 100 mg/day until month 6-8) and evaluated clinically and serologically, up to 3.5 years post-therapy, using Dot-blot and ELISA for measuring the titers of IgG, IgA and IgM anti-P. brasiliensis antibodies and Western-blot for determining IgG, IgA and IgM antibodies against the antigen components of the fungus. Before treatment, 81.5% (Dot-blot) and 84% (ELISA) of the patients presented elevated IgG anti-P. brasiliensis antibody titers which dropped slightly with treatment. On the other hand, the percentages of pre-treatment high-titered sera for IgA and IgM anti-P.brasiliensis were lower (5l.9% and 5l.8%: Dot-blot; 16.5 and 36%: ELISA, respectively) but the titers tended to become negative more frequently with treatment. Prior to treatment, the percentages of positivity for IgG, IgA and IgM anti-P.brasiliensis antibodies in Western-blot were 96%, 20.8% and 41.6%, respectively. Antigens with molecular weights varying from 16-78 kDa, from 21-76 kDa and from 27-78 kDa were reactive for IgG, IgA and IgM antibodies, respectively. The most frequently reactive antigenic components had molecular weights of 27, 33 and 43 kDa for IgG, and 70 for IgA and IgM antibodies. During the period of study, the patients responded well to treatment. The present data confirm the diversity and complexity of the humoral response in PCM, and the importance of utilizing different serological tests to detect IgG, IgA and IgM anti-P. brasiliensis antibodies
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44

Pisil, Yalcin, Zafer Yazici, Hisatoshi Shida, and Tomoyuki Miura. "Is SARS-CoV-2 Neutralized More Effectively by IgM and IgA than IgG Having the Same Fab Region?" Pathogens 10, no. 6 (June 13, 2021): 751. http://dx.doi.org/10.3390/pathogens10060751.

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Recently, recombinant monoclonal antibodies (mAbs) of three Ig isotypes (IgG, IgA, and IgM) sharing the same anti-spike protein Fab region were developed; we evaluated their neutralizing abilities using a pseudo-typed lentivirus coated with the SARS-CoV-2 spike protein and ACE2-transfected cat Crandell–Rees feline kidney cells as the host cell line. Although each of the anti-SARS-CoV-2 mAbs was able to neutralize the spike-coated lentiviruses, IgM and IgA neutralized the viral particles at 225-fold and 125-fold lower concentrations, respectively, than that of IgG. Our finding that the neutralization ability of Igs with the same Fab domain was dramatically higher for IgM and IgA than IgG mAbs suggests a strategy for developing effective and affordable antibody therapies for COVID-19. The efficient neutralization conferred by IgM and IgA mAbs can be explained by their capacity to bind multiple virions. While several IgG mAbs have been approved as therapeutics by the FDA, there are currently no IgM or IgA mAbs available. We suggest that mAbs with multiple antigen-binding sites such as IgM and IgA could be developed as the new generation of therapy.
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45

Mihu, Alin Gabriel, Maria Alina Lupu, Alexandru Nesiu, Daniela Teodora Marti, and Tudor Rares Olariu. "Screening for the Detection of Toxoplasma gondii IgG, IgM and IgA in Females of Reproductive Age from Western Romania." Life 12, no. 11 (November 2, 2022): 1771. http://dx.doi.org/10.3390/life12111771.

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Toxoplasma gondii, a zoonotic protozoan parasite, has the capacity to infect the fetus if the pregnant woman primarily acquires the infection during pregnancy. We evaluated the prevalence of T. gondii IgG, IgM and IgA antibodies in women of reproductive age residing in Western Romania. We also assessed the value of adding a T. gondii IgA test to the serologic panel for the diagnosis of toxoplasmosis, including the detection of a recently acquired infection. Serologic testing to demonstrate the presence of T. gondii IgG antibodies was conducted in 1317 females aged 15–45 years. T. gondii IgM and IgA antibody tests were performed in those with detectable IgG antibodies and IgG avidity test was performed if IgM and/or IgA screening test results were positive. T. gondii IgG were detected in 607 (46.09%; 95%CI: 43.41–48.79) of 1317 study participants and IgG seroprevalence tended to increase with age from 35.44% (95%CI: 29.89–41.30) in age group 15–24 years to 62.85% (95%CI: 56.57–68.82) in age group 35–45 years, showing a significant age-associated increase (p < 0.001). Of the 607 persons with detectable T. gondii IgG antibodies, T. gondii IgM antibodies were demonstrated in 8.90% (95%CI: 6.88–11.43), T. gondii IgA in 1.65% (95%CI: 0.90–3.01) and both T. gondii IgM and IgA in 0.99% (95%CI: 0.45–2.14). The prevalence of IgA antibodies tended to decrease with increasing avidity, from 75% (95%CI: 19.41–99.37) in samples with low avidity to 11.76% (95%CI: 4.44–23.87) in those with high avidity (p = 0.01). Of the study participants who were positive for both T. gondii IgM and IgA antibodies, 66.67% had low or equivocal IgG avidity test results compared to 6.25% who tested positive for IgM, were negative for IgA and in whom low or equivocal IgG avidity test results were noted (p = 0.001). This study indicates that in Western Romania, T. gondii IgG seroprevalence is high in females of reproductive age and T. gondii IgA antibodies may be rarely detected during a serologic screening. However, in individuals with demonstrable T. gondii IgG and IgM antibodies, testing for T. gondii IgA may improve the rate for the detection of a recently acquired toxoplasmosis.
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46

Huber, Timo, Philipp Steininger, Pascal Irrgang, Klaus Korn, Matthias Tenbusch, Katharina Diesch, Susanne Achenbach, et al. "Diagnostic performance of four SARS-CoV-2 antibody assays in patients with COVID-19 or with bacterial and non-SARS-CoV-2 viral respiratory infections." European Journal of Clinical Microbiology & Infectious Diseases 40, no. 9 (June 9, 2021): 1983–97. http://dx.doi.org/10.1007/s10096-021-04285-4.

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AbstractSARS-CoV-2 antibody assays are used for epidemiological studies and for the assessment of vaccine responses in highly vulnerable patients. So far, data on cross-reactivity of SARS-CoV-2 antibody assays is limited. Here, we compared four enzyme-linked immunosorbent assays (ELISAs; Vircell SARS-CoV-2 IgM/IgA and IgG, Euroimmun SARS-CoV-2 IgA and IgG) for detection of anti-SARS-CoV-2 antibodies in 207 patients with COVID-19, 178 patients with serological evidence of different bacterial infections, 107 patients with confirmed viral respiratory disease, and 80 controls from the pre-COVID-19 era. In COVID-19 patients, the assays showed highest sensitivity in week 3 (Vircell-IgM/A and Euroimmun-IgA: 78.9% each) and after week 7 (Vircell-IgG: 97.9%; Euroimmun-IgG: 92.1%). The antibody indices were higher in patients with fatal disease. In general, IgM/IgA assays had only limited or no benefit over IgG assays. In patients with non-SARS-CoV-2 respiratory infections, IgG assays were more specific than IgM/IgA assays, and bacterial infections were associated with more false-positive results than viral infections. The specificities in bacterial and viral infections were 68.0 and 81.3% (Vircell-IgM/IgA), 84.8 and 96.3% (Euroimmun-IgA), 97.8 and 86.0% (Vircell-IgG), and 97.8 and 99.1% (Euroimmun-IgG), respectively. Sera from patients positive for antibodies against Mycoplasma pneumoniae, Chlamydia psittaci, and Legionella pneumophila yielded particularly high rates of unspecific false-positive results in the IgM/IgA assays, which was revealed by applying a highly specific flow-cytometric assay using HEK 293 T cells expressing the SARS-CoV-2 spike protein. Positive results obtained with anti-SARS-CoV-2 IgM/IgA ELISAs require careful interpretation, especially if there is evidence for prior bacterial respiratory infections.
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47

Freitas, Jaqueline Aparecida Gleice de, Mariana Félix de Souza Prudente, and Mara Silvia Carvalhaes. "Experimental lagochilascariosis in X-chromosome-linked immunodeficient mice." Revista da Sociedade Brasileira de Medicina Tropical 42, no. 4 (August 2009): 381–85. http://dx.doi.org/10.1590/s0037-86822009000400005.

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Lagochilascaris minor is the etiological agent of lagochilascariosis, a disease that affects the neck region and causes exudative abscesses, with eggs, adult parasites and L3/L4 larvae in the purulent exudates. Mice are now considered to be intermediate hosts for the parasite. To determine the pattern of infection in B1 cell-deficient mice, experimental lagochilascariosis was studied in BALB/c and X-chromosome-linked immunodeficient (xid) mice. BALB.xid-infected mice showed lower numbers of larvae. Third-stage larvae, fourth-stage larvae and adult parasites were found in both strains. BALB/c mice produced IgM, IgG, IgA and IgE against the crude extract and secreted/excreted antigens of the parasite. On the other hand, BALB.xid mice did not produce IgM and produced lower levels of IgG and IgA, and similar quantities of IgE.
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48

Vandekerckhove, B. A., D. Jones, J. Punnonen, D. Schols, H. C. Lin, B. Duncan, R. Bacchetta, J. E. de Vries, and M. G. Roncarolo. "Human Ig production and isotype switching in severe combined immunodeficient-human mice." Journal of Immunology 151, no. 1 (July 1, 1993): 128–37. http://dx.doi.org/10.4049/jimmunol.151.1.128.

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Abstract Severe combined immunodeficient (SCID) mice were transplanted with different human fetal organs (SCID-hu mice), including thymus, liver, spleen, and omentum, and the serum levels of human IgM, IgG, IgE, and IgA were measured. In all SCID-hu mice significant levels (up to 590 ng/ml) of IgM were detected, irrespective of the organs transplanted. In contrast, IgG was present (up to 530 ng/ml) only when the fetal thymus was transplanted together with the fetal liver, indicating that the presence of human T cell is a prerequisite for in vivo isotypes switching by human B cells in SCID-hu mice. Additional transplantation of fetal spleen did not significantly increase IgG levels. was observed 4 months after transplantation. At that time, analysis by IEF showed that human IgG present in SCID-hu serum was at least oligoclonal. Furthermore, all IgG subclasses were represented in the human IgG pool. Human B cells were undetectable in the peripheral blood, spleen, and bone marrow of these SCID-hu mice; in contrast, B cells expressing CD19 could be isolated from the SCID-hu thymus. Considerable proportions of the CD19+ B cells coexpressed CD5, CD7, CD10, CD40, and CD2. These B cells spontaneously produced IgM and IgG in vitro and could be induced to switch to IgE-producing cells when cocultured with cloned activated CD4+ T cells in the presence of IL-4. Collectively, these data demonstrate that functionally mature B cells able to produce IgM and IgG in vivo, and IgE in vitro, are present in the SCID-hu human thymus.
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49

Harriman, Gregory R., Molly Bogue, Pamela Rogers, Milton Finegold, Susan Pacheco, Allan Bradley, Yongxin Zhang, and Innocent N. Mbawuike. "Targeted Deletion of the IgA Constant Region in Mice Leads to IgA Deficiency with Alterations in Expression of Other Ig Isotypes." Journal of Immunology 162, no. 5 (March 1, 1999): 2521–29. http://dx.doi.org/10.4049/jimmunol.162.5.2521.

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Abstract A murine model of IgA deficiency has been established by targeted deletion of the IgA switch and constant regions in embryonic stem cells. B cells from IgA-deficient mice were incapable of producing IgA in vitro in response to TGF-β. IgA-deficient mice expressed higher levels of IgM and IgG in serum and gastrointestinal secretions and decreased levels of IgE in serum and pulmonary secretions. Expression of IgG subclasses was complex, with the most consistent finding being an increase in IgG2b and a decrease in IgG3 in serum and secretions. No detectable IgA Abs were observed following mucosal immunization against influenza; however, compared with those in wild-type mice, increased levels of IgM Abs were seen in both serum and secretions. Development of lymphoid tissues as well as T and B lymphocyte function appeared normal otherwise. Peyer’s patches in IgA-deficient mice were well developed with prominent germinal centers despite the absence of IgA in these germinal centers or intestinal lamina propria. Lymphocytes from IgA-deficient mice responded to T and B cell mitogens comparable to those of wild-type mice, while T cells from IgA-deficient mice produced comparable levels of IFN-γ and IL-4 mRNA and protein. In conclusion, mice with targeted deletion of the IgA switch and constant regions are completely deficient in IgA and exhibit altered expression of other Ig isotypes, notably IgM, IgG2b, IgG3, and IgE, but otherwise have normal lymphocyte development, proliferative responses, and cytokine production.
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50

Zhao, W. G., Y. C. Yu, Y. D. Li, X. H. Xu, D. X. Zhu, and S. W. Xie. "Cerebrospinal fluid IgG, IgA, IgM, IgD and IgE levels in the healthy individuals with related parameters analysis." Journal of Neuroimmunology 16, no. 1 (September 1987): 194. http://dx.doi.org/10.1016/0165-5728(87)90432-2.

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