Frequency Of IgA Research Articles

Mast cells help organize the Peyer's patch niche for induction of IgA responses.

Peyer's patches (PPs) are lymphoid structures situated adjacent to the intestinal epithelium that support B cell responses that give rise to many intestinal IgA-secreting cells. Induction of isotype switching to IgA in PPs requires interactions between B cells and TGFβ-activating conventional dendritic cells type 2 (cDC2s) in the subepithelial dome (SED). However, the mechanisms promoting cDC2 positioning in the SED are unclear. Here, we found that PP cDC2s express GPR35, a receptor that promotes cell migration in response to various metabolites, including 5-hydroxyindoleacetic acid (5-HIAA). In mice lacking GPR35, fewer cDC2s were found in the SED, and frequencies of IgA+ germinal center (GC) B cells were reduced. IgA plasma cells were reduced in both the PPs and lamina propria. These phenotypes were also observed in chimeric mice that lacked GPR35 selectively in cDCs. GPR35 deficiency led to reduced coating of commensal bacteria with IgA and reduced IgA responses to cholera toxin. Mast cells were present in the SED, and mast cell-deficient mice had reduced PP cDC2s and IgA+ cells. Ablation of tryptophan hydroxylase 1 (Tph1) in mast cells to prevent their production of 5-HIAA similarly led to reduced PP cDC2s and IgA responses. Thus, mast cell-guided positioning of GPR35+ cDC2s in the PP SED supports induction of intestinal IgA responses.

Distinct and shared B cell responses of tuberculosis patients and their household contacts.

This study was aimed at identifying the B cell responses which could distinguish between 'latent tuberculosis infection (LTBI)' and active TB disease. Study subjects were smear-positive TB patients (n = 54) and their disease-free household contacts (HHCs, n = 120). The sera were used for determination of antibody levels (ΔOD values) against Mycobacterium tuberculosis membrane (MtM) antigens by ELISA and for visualisation of seroreactive MtM antigens by immunoblotting. B cell subsets in whole blood samples were determined by flow cytometry. In TB sera, levels of IgG antibodies were significantly higher than IgM and IgA whereas IgM and IgA antibody levels were comparable. Conversely, HHC sera had significantly higher IgM antibody levels than IgG and IgA. The ratio of IgM to IgG antibodies in HHCs were also significantly higher than in patients. Immunoblotting revealed that some of the MtM antigens (<10, ~12 and ~25 kDa) reacted with TB as well as HHC sera whereas some other antigens (~16, ~36, ~45 and ~60 kDa) reacted with most of TB and a subset of HHC sera. Frequencies of classical memory B cells (cMBCs, CD19+CD27+) were significantly higher, and of IgG+ cMBCs were significantly lower in HHCs than in patients. Frequencies of IgA+ cMBCs in HHCs and patients were comparable but both were significantly higher than the corresponding frequencies of IgG+ cMBCs. Frequencies of IgA+ atypical MBCs (aMBCs, CD19+CD27-) in HHCs and patients were also comparable and significantly higher than the IgG+ aMBCs. The plasmablast (CD19+CD27++CD38++) frequencies in HHCs and patients were comparable. These results suggest that the IgM/IgG antibody ratio, antibody binding to selected MtM antigens and relative frequencies of MBC subsets could indicate protective or pathogenic immune responses following the primary infection with Mtb. Responses that orchestrate protection leading to a 'quiescent' LTBI may provide clues to an effective vaccination strategy against TB.

Altered IgA Response to Gut Bacteria Is Associated with Childhood Asthma in Peru.

Alterations in gut microbiota in early life have been associated with the development of asthma; however, the role of gut bacteria or the IgA response to gut bacteria in school-aged children with asthma is unclear. To address this question, we profiled the microbial populations in fecal and nasal swab samples by 16S rRNA sequencing from 40 asthma and 40 control children aged 9-17 y from Peru. Clinical history and laboratory evaluation of asthma and allergy were obtained. Fecal samples were analyzed by flow cytometry and sorted into IgA+ and IgA- subsets for 16S rRNA sequencing. We found that the fecal or nasal microbial 16S rRNA diversity and frequency of IgA+ fecal bacteria did not differ between children with or without asthma. However, the α diversity of fecal IgA+ bacteria was decreased in asthma compared with control. Machine learning analysis of fecal bacterial IgA-enrichment data revealed loss of IgA binding to the Blautia, Ruminococcus, and Lachnospiraceae taxa in children with asthma compared with controls. In addition, this loss of IgA binding was associated with worse asthma control (Asthma Control Test) and increased odds of severe as opposed to mild to moderate asthma. Thus, despite little to no change in the microbiota, children with asthma exhibit an altered host IgA response to gut bacteria compared with control participants. Notably, the signature of altered IgA responses is loss of IgA binding, in particular to members of Clostridia spp., which is associated with greater severity of asthma.

Asthma-Associated Long TSLP Inhibits the Production of IgA.

Thymic stromal lymphopoietin (TSLP) contributes to asthmatic disease. The concentrations of protective IgA may be reduced in the respiratory tract of asthma patients. We investigated how homeostatic short TSLP (shTSLP) and asthma-associated long TSLP (loTSLP) regulate IgA production. B cells from healthy donors were stimulated in the presence or absence of shTSLP or loTSLP; the concentrations of IgA, IgM, IgE, and IgG antibodies were determined in cell culture supernatants; and B cells were analyzed by flow cytometry. LoTSLP, but not shTSLP, suppressed the secretion of IgA but not of IgE. The type 2 cytokine IL-4, which in addition to loTSLP contributes to asthmatic disease, did not affect the production of IgA or the frequency of IgA+ B cells. Instead, IL-4 increased IgG production, especially of the subclasses IgG2 and IgG4. LoTSLP inhibited IgA secretion by sorted memory B cells but not by naïve B cells. Although loTSLP inhibited IgA production, the vitamin A metabolite retinoic acid promoted the secretion of IgA, also in the presence of loTSLP, suggesting that vitamin A may promote IgA production in asthma. Our data demonstrate that asthma-associated loTSLP negatively regulates the secretion of IgA, which may negatively impact the surveillance of mucosal surfaces in asthma.

Krüppel-Like-Factor 2, a new player in mucosal IgA homeostasis

Abstract Krüppel-Like-Factor 2 (KLF2) is a transcription factor that controls organ development, differentiation and trafficking of cells. In the immune system, KLF2 fosters the egress of T lymphocytes from the thymus via S1PR1 and promotes quiescent states of B lymphocytes as well as homing of antigen-specific IgG plasmablasts (PB) and plasma cells (PC) to the bone marrow (BM) via the α4β7 receptor. To investigate the PC-specific role of KLF2, we analyzed CD138+/TACI+ PB/PC subpopulations and isotype changes in various organs such as spleen (SP), BM, gut associated lymphoid tissues (GALT) and blood of KLF2-deficient mice in comparison to their mb1cre+ KLF2wt/wt controls. Therefore, FACS and Elispot analyses showed a striking reduction of IgA+ PB/PC in SP, BM and blood of non-immunized mice. Elisa and multiplex data revealed a strong reduction in serum IgA as well as (s)IgA in the feces of KLF2-deficient mice. However, frequencies of IgA+ PB/PC were not changed in GALT but total PB/PC accumulated in mesenteric lymph nodes (mLN) and Peyer’s Patches. In addition, IgA secretion of these cells was not effected. Based on these data, we conclude that the observed IgA-deficiency in KLF2-deficient mice can in part be explained by impaired egress of class switched PB/PC from their organ of generation to survival niches in the bone marrow and gut by controlling the expression of integrins. To address the consequences of a dysregulated PB/PC migration during infection, we are analyzing a GALT-dependent immunization with recombinant Flagellin which is known to trigger a systemic IgG as well as an mucosal IgA response. Furthermore, we are identifying KLF2 target genes that control PC egress and trafficking by RNAseq of IgA+ PB/PC from the mLN of KLF2-deficient mice.

Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course.

Background:In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts.Methods:In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. The lower limits of normal (LLN) for serum Ig concentration were IgG < 700 mg/dl, IgM < 40 mg/dl, and IgA < 70 mg/dl. Mann–Whitney U test, analysis of variance test, and multiple linear regression analysis were employed.Results:In total, 327 MS patients were retrospectively identified (Bern/Athens: n = 226/101). Serum IgG concentrations were frequently under LLN in both MS cohorts (Bern/Athens: 15.5%/14.9%), even when considering only untreated patients (Bern/Athens: 7.9%/8.6%). MS patients (n = 327) were significantly more likely to have IgG concentrations below LLN and below 600 mg/dl in comparison with controls (n = 58) (p = 0.015 and 0.047, respectively). Between both patient groups, no significant differences were found in frequencies of IgA and IgM concentrations under LLN [n (MS patients/controls): IgA 203/30, IgM 224/24]. Independently of age, secondary progressive MS patients had lower IgG concentrations than relapsing–remitting and primary progressive patients (both: p ⩽ 0.01). After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab (p = 0.001; n = 42/327), intravenous corticosteroids (p < 0.001; n = 16/327), natalizumab (p < 0.001; n = 48/327), and fingolimod (p = 0.003; n = 6/327).Conclusion:Our study demonstrated high prevalence rates of reduced serum IgG concentrations in MS patients with and without disease-modifying treatments. The significance of lower IgG concentrations at the levels noted is unclear considering that infections or interference with antibody production generally occur when IgG levels are much lower, at or below 400 mg/dl. However, the information is useful to monitor IgG levels especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl.

A Phase 1 dose escalating study of double mutant heat-labile toxin LTR192G/L211A (dmLT) from Enterotoxigenic Escherichia coli (ETEC) by sublingual or oral immunization

BackgroundThe public health burden of Enterotoxigenic Escherichia coli (ETEC) is high but no vaccine is specifically approved to prevent ETEC infections. MethodsWe performed a Phase 1, dose escalation study (1–50 µg) evaluating the sublingual (SL) delivery of the double mutant heat-labile toxin LTR192G/L211A (dmLT) in 80 healthy adult volunteers. The primary objective was safety and the secondary was the immunogenicity of the dmLT. Subjects received 3 doses of dmLT at days 1, 15, and 29. Subjects receiving the first dose at each dosage level were observed overnight in a research facility. The second and third doses were administered on an outpatient basis. Data from cohorts 1–4 were used to select the cohort 5 dose (25 µg), comparing SL and oral routes. ResultsThe vaccine appeared safe and well tolerated with only rare development of vomiting or diarrhea. The serum anti-dmLT IgA and IgG and neutralizing antibody responses were modest after any of the SL immunizations. Serum IgA and IgG titers were increased at the higher antigen doses (25 or 50 µg) but the percent with 4-fold increases was at best 38% for both IgA and IgG. The 4-fold increase among subjects receiving all 3 doses was 43% for both IgA and IgG. Antibody titers following oral administration were, in general, significantly higher than after SL. The frequency of IgA- or IgG-ASCs in circulation were somewhat vaccine dose dependent and were detected at a moderate level. However, antibodies in saliva or stool were rarely detected. Post-vaccination increases in T cells or cytokine production were also infrequent. ConclusionThe dmLT vaccine formulation evaluated here was safe but only moderately immunogenic at doses up to 50 µg when administered by the SL or oral route. Studies at higher doses with better formulations appear warranted.

Role of Der p 1–specific B cells in immune tolerance during 2 years of house dust mite–specific immunotherapy

Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. Allergen-specific B-cell responses during 2years of house dust mite AIT were compared between responder and nonresponder patients. B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG1- and IgG4-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23±0.28 to 2.45±0.24 (P=.001) and a decrease in skin prick test reactivity to house dust mite from 7.0±1.3 to 2.7±0.5mm(P=.001). IgG4+ and IgA+ Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG4+ but not the IgA+ fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2years. The increased frequency of Der p 1-specific IgG4+ B cells, plasmablasts, and IL-10+ and dual-positive IL-10+IL-1RA+ Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG4-expressing Der p 1-specific B cells, plasmablasts, and IL-10+ and/or IL-1RA+ Breg cells.

Murine γδ T Cells Render B Cells Refractory to Commitment of IgA Isotype Switching.

γδ T cells are abundant in the gut mucosa and play an important role in adaptive immunity as well as innate immunity. Although γδ T cells are supposed to be associated with the enhancement of Ab production, the status of γδ T cells, particularly in the synthesis of IgA isotype, remains unclear. We compared Ig expression in T cell receptor delta chain deficient (TCRδ−/−) mice with wild-type mice. The amount of IgA in fecal pellets was substantially elevated in TCRδ−/− mice. This was paralleled by an increase in surface IgA expression and total IgA production by Peyer's patches (PPs) and mesenteric lymph node (MLN) cells. Likewise, the TCRδ−/− mice produced much higher levels of serum IgA isotype. Here, surface IgA expression and number of IgA secreting cells were also elevated in the culture of spleen and bone marrow (BM) B cells. Germ-line α transcript, an indicator of IgA class switch recombination, higher in PP and MLN B cells from TCRδ−/− mice, while it was not seen in inactivated B cells. Nevertheless, the frequency of IgA+ B cells was much higher in the spleen from TCRδ−/− mice. These results suggest that γδ T cells control the early phase of B cells, in order to prevent unnecessary IgA isotype switching. Furthermore, this regulatory role of γδ T cells had lasting effects on the long-lived IgA-producing plasma cells in the BM.

Green tea cultivar ‘Benifuuki’ potentiates split vaccine-induced immunoglobulin A production

Influenza is a widespread disease caused by infection with the influenza virus. Vaccination is considered to be the main countermeasure against influenza. A split vaccine is widely used to avoid severe adverse events, and it induces strong humoral immunity. However, the split vaccine alone cannot elicit mucosal immunity, including IgA production, and its preventative effects are limited. Here, we show that the green tea cultivar 'Benifuuki' extract enhanced the effect of a split vaccine on mucosal immunity. The frequency of IgA+ cells was increased in lung and Peyer's patch that received Benifuuki diet. Secretion of hemagglutinin-specific mucosal IgA, which is closely linked to the prevention of viral infection, was significantly increased in the bronchoalveolar lavage fluid of split vaccine-immunized BALB/c mice that were administered green tea Benifuuki extract. Our findings suggest that Benifuuki intake enhanced the effects of the split vaccine on mucosal immunity.

Fact or Fiction? Examining a Role for N-Methyl-D-Aspartate Receptor Autoantibodies in Psychiatric Illness

Fact or Fiction? Examining a Role for N-Methyl-D-Aspartate Receptor Autoantibodies in Psychiatric Illness

Age-related differences in human palatine tonsillar B cell subsets and immunoglobulin isotypes.

The tonsils provide defense of the upper aerodigestive tract against pathogens. Although long known to undergo functional changes with age, the precise changes occurring within tonsillar B cell populations remain undefined. In the present study, we investigated age-related changes in palatine tonsillar B cell subsets and immunoglobulin (Ig) isotypes. Palatine tonsils were obtained from forty-two tonsillectomy patients without tonsillitis who were divided into three groups: young children (4-9 years), adolescents (10-19 years), and adults (20-60 years). Tonsillar B cells were then analyzed by flow cytometry. Using expression of CD38 and IgD to define B cell subsets, we found that the frequency of germinal center (GC) B cells in the tonsils was significantly higher, and the frequency of memory B cells lower, in young children as compared to adolescents and adults. Within the GC B cell subsets, adults had a higher frequency of IgA(+) cells and a lower frequency of IgM(+) cells as compared to individuals in the younger age groups. Moreover, young children had a higher frequency of IgG(+) cells in the GC B cell subsets than did individuals in the older age groups. We also observed an abundance of IgM(+) cells among memory B cells and plasmablasts in young children and IgA(+) cells in adults. In summary, the proportion of GC B cells in palatine tonsillar B cells decreases with age, while the proportion of memory B cells increases with age. In addition, Ig isotypes in tonsils preferentially switch from IgM to IgA as individuals age.

Immunological status of the progeny of breeder hens kept on ochratoxin A (OTA)- and aflatoxin B1 (AFB1)-contaminated feeds

This study aimed to evaluate the immunological status of progeny of hens kept on ochratoxin A (OTA)- and aflatoxin B1 (AFB1)-contaminated feed. For this purpose, White Leghorn (WL) layer breeder hens (40-weeks-of-age) were divided into six groups (A–F). Hens in Group A were fed a commercial layer ration while those in Groups B and C were kept on a diet amended with 3 and 5 mg OTA/Kg, respectively. Group D was fed a ration containing 5 mg AFB1/Kg, while hens in Groups E and F were kept on feed amended with OTA and AFB1 each. All feedings were for 1, 2, or 3 weeks. Fertile eggs were set for hatching on a weekly basis to obtain progeny of each week separately. At 14 days-of-age, subsets of progeny were euthanized and the frequency of immunoglobulin(s)-bearing cells in their spleen and bursa of Fabricius assessed; at 16 days-of-age, other chicks in each set were utilized to determine their lymphoblastogenic responses against phytohemagglutinin (PHA-P). At 30 days-of-age, the final sub-set of chicks/group was euthanized and their peritoneal macrophages harvested for measurements of phagocytic potential and nitrite production. Relative weights of the bursa of Fabricius and of the spleen were significantly lower in the progeny of hens fed mycotoxin-contaminated diets for 14 and 21 days. The frequencies of IgA-, IgG-, and IgM-bearing cells were also significantly lower in the bursa of Fabricius and spleen of progeny chicks obtained from hens fed the OTA + AFB1 mixed diet. Feeding contaminated diets to breeder hens also resulted in significantly lower responses to PHA-P. In addition, the percentages of peritoneal macrophages displaying phagocytosis of sheep red blood cells (SRBC), the number of SRBC/macrophage, and nitrite production were each significantly lower in cells from progeny chicks from OTA- and AFB1-fed hens. The findings of the present study indicated there were severe immunosuppressive effects in progeny chicks as a result of exposure of their parent hens to OTA and AFB1 either alone or in combination. These studies provide emphasis for the need for mycotoxin regulation policy with respect to the ingredients used in poultry feed, since it is clear that feeding multi-mycotoxin-contaminated diets to breeder hens will almost certainly result in the hatching of manifestly unhealthy chicks.

Immunological status of the progeny of breeder hens kept on ochratoxin A (OTA)-contaminated feed

This study aimed to evaluate the immunological status of the progeny of breeder hens kept on ochratoxin A (OTA)-contaminated feed. For this purpose, 84 White Leghorn (WL) layer breeder hens (40-weeks-of-age) were divided into seven groups (A–G). Hens in the Group A were fed a commercial layer ration while those in Groups B–G were kept on a diet amended with 0.1, 0.5, 1.0, 3.0, 5.0, or 10.0 mg OTA/kg, respectively, for 3 weeks. Fertile eggs were set for hatching on the weekly basis to get the progeny of each week separately. Hatched chicks (n = 10 from each group) were euthanized at Day 14 of age, and their immunological organs weighed and fixed in neutral buffered formalin. An indirect immunoperoxidase method was applied to study the frequency of immunoglobulin(s)-bearing cells in the spleen and bursa of Fabricius from these progeny. From other chicks within each set, at Day 16 of age, lymphoblastogenic responses against an intradermal administration of phytohemagglutinin (PHA-P) were determined. Relative weights of the bursa of Fabricius and of the thymus were significantly lower in the progeny of hens fed OTA-contaminated diet for 14 and 21 days. The frequencies of IgA-, IgG-, and IgM-bearing cells were also significantly (P ≤ 0.05) lower in the bursa of Fabricius and spleen of the progeny chicks obtained from dams fed the OTA-mixed diet. Progeny chicks obtained from the breeder hens fed higher doses of OTA showed significantly lower responses to PHA-P than did counterpart chicks from control hens. The findings of this study suggested that there were immunosuppressive effects from OTA in the progeny obtained from breeder hens kept on OTA-contaminated diets.

IgA antibodies to Chlamydia trachomatis and metabolic syndrome

Chlamydia pneumoniae may trigger atherogenesis. Chlamydia trachomatis (CT) can also induce endothelial activation. However, its role in metabolic syndrome (METS), a proatherogenic entity, has remained unexplored. In this study the frequencies of IgA and IgG anti-CT antibodies were evaluated by immunoenzymatic assay in METS patients and healthy controls. The survey included 238 individuals (148 with METS). The mean age was 59.7 years. IgA anti-CT antibodies were found significantly more frequently in METS patients (16.9%) than in controls (5.6%) (P= 0.015). The role of such IgA response in METS should be further investigated.

Meningococcal serogroup C polysaccharide specific memory B cells, directly enumerated by labeled polysaccharide, are not affected by age at vaccination

The influence of age on the generation and persistence of specific memory B cells after vaccination with Neisseria meningitidis type C polysaccharide (MenC-PS) conjugate is unknown. MenC-PS-specific B cells could be directly enumerated by fluorochrome-labeled MenC-PS and flow cytometry in blood up to at least 4 years after vaccination, ranging from 0.01% to 0.78% of total B cells and did not correlate with age at vaccination. The percentage of MenC-specific memory B cells out of total memory B cells correlated with total MenC-specific B-cells and with frequencies of IgA + plus IgG + MenC-specific AbSC, but not with MenC-specific Ab.

Detection of anti-SS-A/Ro and anti-SS-B/La antibodies of IgA and IgG isotypes in saliva and sera of patients with Sjögren's syndrome.

To assess the frequency and the possibility of local production of autoantibodies against SS-A/Ro and SS-B/La in patients with primary Sjögren's syndrome (SS), serum and saliva samples were obtained from 42 patients with SS, 10 with rheumatoid arthritis without sicca syndrome, and 12 healthy volunteers. Autoantibodies were detected using enzyme-linked immunosorbent assay and immunoblotting. The frequencies of IgA anti-SS-A antibody, IgA anti-SS-B antibody, IgG anti-SS-A antibody and IgG anti-SS-B antibody in serum from SS patients were 45%, 50%, 43% and 21%, respectively. The frequencies of IgA anti-SS-A antibody, IgA anti-SS-B antibody, IgG anti-SS-A antibody and IgG anti-SS-B antibody in saliva from SS patients were 31%, 33%, 40%, and 19%, respectively. We also found secretory IgA anti-SS-A and anti-SS-B antibodies accompanying secretory components in saliva and sera in representative SS patients. Significant correlations were found between serum and salivary levels of IgA anti-SS-A antibodies, and between serum and salivary levels of IgA anti-SS-B antibodies in SS patients. Significant correlations were also found between serum and salivary levels of IgG anti-SS-A antibodies, and between serum and salivary levels of IgG anti-SS-B antibodies in SS patients. Immunoblot analysis confirmed the presence of IgA-class autoantibodies against SS-A and SS-B in saliva and serum from representative patients. The presence of IgA- and IgG-class autoantibodies against SS-A and SS-B and those accompanying secretory components in saliva from SS patients suggests the local production of these antibodies and the relationship between local and systemic antibody responses.

Significance of incidental mesangial IgA deposition in minimal change nephrotic syndrome

Background: Incidental IgA deposition in glomerular mesangium exists in 10–20% of autopsy kidneys1, 2 or renal allograft donors.3 In the present study, we examined the clinicopathological features of incidental mesangial IgA deposition in renal biopsy from patients with minimal change nephrotic syndrome (MCNS) to understand the significance of mesangial IgA deposition in MCNS and pathogenesis of IgA nephropathy. Patients and Methods: From January 1994 to September 2000, 63 patients were diagnosed with MCNS by renal biopsy at Kidney Center, Tokyo Women’s Medical University. Mesangial IgA and C3 deposition was examined by immunofluorescence staining using frozen sections. The frequency of IgA and C3 deposition in MCNS and clinicopathological features of IgA-positive patients with MCNS were investigated. Results: The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%) (Fig. 1). The serum IgA concentration was significantly higher in the IgA-positive patients than in the IgA-negative patients (309 ± 75 mg/dL versus 245 ± 106 mg/dL, P = 0.043) (Fig. 2). The urinary red blood cell count was higher in IgA-positive patients than in IgA-negative patients, although not significantly different (11.7 ± 12.7 counts/HPF versus 5.3 ± 4.0 counts/HPF, P = 0.067) (Fig. 3). Other clinical parameters (age, sex, amount of proteinuria, serum creatinine and creatinine clearance) were not significantly different. Histologically, no significant differences were observed between IgA-positive and IgA-negative patients in following parameters: grade of mesangial cell proliferation and mesangial matrix increase, extents of tubular atrophy and interstitial fibrosis and grade of vascular sclerosis. After steroid treatment, all 15 patients with mesangial IgA deposition had become complete remission, although three patients once relapsed proteinuria. The haematuria also disappeared after steroid treatment in these patients. Figure 1Open in figure viewerPowerPoint The frequency of mesangial IgA and C3 deposition in MCNS patients (n = 63). The mesangial IgA deposition was present in 15 out of 63 patients (23.8%). Among these 15 patients, codeposition of C3 was present in 10 patients (66.7%). Figure 2Open in figure viewerPowerPoint The serum IgA concentration of the MCNS patients with and without mesangial IgA deposition. The serum IgA concentration was significantly higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48) (309 ± 75 mg/dL vs 245 ± 106 mg/dL, P = 0.043). Figure 3Open in figure viewerPowerPoint The urinary red blood cell counts of the MCNS patients with and without mesangial IgA deposition. The urinary red blood cell count was higher in IgA-positive patients (n = 15) than in IgA-negative patients (n = 48), although not significantly different (11.7 ± 12.7 counts/HPF vs 5.3 ± 4.0 counts/HPF, P = 0.067). Conclusion: The incidental mesangial IgA deposition was frequently observed in MCNS patients (15/60 patients, 23.8%). The phenomenon of mesangial IgA deposition in MCNS patients was related to higher serum IgA concentration and might cause slight haematuria. However, no influence of mesangial IgA deposition was found on the renal function and the clinical outcome of MCNS after treatment.

The Immunohistology of IgA Nephropathy

The glomerular immunohistologic characteristics of 180 patients with IgA nephropathy (IgAN), defined by 2+ or greater (out of 0 to 4+) mesangial IgA-dominant or codominant immunostaining and no evidence for systemic lupus erythematosus, were compared with those of 84 patients with proliferative lupus glomerulonephritis and 254 patients with other forms of proliferative glomerulonephritis. The IgAN population increased in number by only 5% if the IgA immunostaining criterion was lowered to 1+, and it decreased by only 2% if IgA codominant staining was disallowed. A distinctive immunohistologic feature of IgAN in comparison with other immune complex-mediated glomerulopathies, in addition to the predominance of IgA immunostaining, was a high frequency (67%) of patients with greater lambda- than kappa-immunoglobulin light chain immunostaining. There was no correlation between the absolute or relative intensities or frequencies of IgA, IgG, or IgM immunostaining and the severity of glomerular disease; however, the presence of capillary wall immune deposits correlated with more severe disease. Terminal complement components were consistently present and were more conspicuous in more severely injured glomeruli. Immunostaining for the early classical complement activation pathway component C1q was absent or scanty in IgAN. This finding was particularly useful in the immunohistologic differentiation of IgAN from proliferative lupus glomerulonephritis, which was the form of glomerulonephritis with the greatest overlap with IgAN with respect to IgA immunostaining. When the diagnostic criteria for IgAN were 2+ or greater, dominant or codominant mesangial IgA immunostaining and less than 2+ C1q immunostaining, an immunohistologic diagnosis of IgAN was made with 98% accuracy.