Elevated Serum IgA Research Articles

A Case of Elevated Serum IgA Levels Complicated with Heart Failure.

A Case of Elevated Serum IgA Levels Complicated with Heart Failure.

Resolution of Henoch-Schönlein purpura nephritis after acquired IgA deficiency

We report a case of Henoch-Schönlein purpura nephritis (HSPN) with acquired IgA deficiency due to parvovirus B19 infection. The patient was diagnosed as having Henoch-Schönlein purpura (HSP) at 6 years old, and subsequently developed macrohematuria and massive proteinuria of 7.4 g/day with decreased creatinine clearance of 70.2 ml/min/1.73 m(2) and significantly elevated serum IgA level of 449 mg/dl. The first kidney biopsy yielded the diagnosis of severe HSPN. After the initiation of the immunosuppressive therapy, the patient was infected with parvovirus B19 and developed virus-associated hemophagocytic syndrome (VAHS). Thereafter, the serum level of IgA selectively decreased and remained undetectable until the present time. Repeated kidney biopsies performed over a period of 14 years revealed a remarkable histological improvement in association with stabilization of the patient's kidney function. Considering the severity of initial kidney injury, persistent acquired IgA deficiency was likely to add favorable effects to the immunosuppressive therapy in this patient with HSPN.

Non-cirrhotic Intrahepatic Portal Hypertension: Associated Gut Diseases and Prognostic Factors

Non-cirrhotic intrahepatic portal hypertension (NCIPH) is generally regarded to have a benign prognosis. We have studied a cohort followed-up at a tertiary referral center and postulate that gut-derived prothrombotic factors may contribute to the pathogenesis and prognosis of NCIPH. We retrospectively analyzed prognostic indicators in 34 NCIPH patients. We also searched for associated gut diseases. Transplant-free survival in NCIPH patients from first presentation with NCIPH at 1, 5, and 10 years was 94% (SE: 4.2%), 84% (6.6%), and 69% (9.8%), respectively. Decompensated liver disease occurred in 53% of patients. Three (9%) patients had ulcerative colitis while five of 31 (16%) tested had celiac disease and on Kaplan-Meier analysis, celiac disease predicted reduced transplant-free survival (p=0.018). On multivariable Cox regression analysis, independent predictors of reduced transplant-free survival were older age at first presentation with NCIPH, hepatic encephalopathy, and portal vein thrombosis. Prevalence of elevated initial serum IgA anticardiolipin antibody (CLPA) was significantly higher in NCIPH (36% of patients tested), compared to Budd-Chiari syndrome (6%) (p=0.032, Fisher's exact test) and celiac disease without concomitant liver disease (0%) (p=0.007). We have identified prognostic factors and report progression to liver failure in 53% of NCIPH patients followed-up at our center. Our data supports a role for intestinal disease in the pathogenesis of intrahepatic portal vein occlusion leading to NCIPH.

IgG4-related disease

IgG4-related disease is a recently recognized systemic syndrome characterized by mass-forming lesions, mainly in exocrine tissue, that consist of lymphoplasmacytic infiltrates and sclerosis. There are numerous IgG4+ plasma cells in the affected tissues, and the serum IgG4 level is elevated in these patients. Ocular adnexal IgG4-related disease frequently involves bilateral lacrimal glands, and obliterative phlebitis is rare. Moreover, some malignant lymphomas, especially mucosa-associated lymphoid tissue lymphoma, arise from ocular adnexal IgG4-related disease. It is known that hyper IL-6 syndromes, such as multicentric Castleman's disease, rheumatoid arthritis, and other autoimmune diseases, fulfill the histological diagnostic criteria for IgG4-related disease; therefore, hyper IL-6 syndromes and IgG4-related disease cannot be differentially diagnosed by immunohistochemical staining alone. However, upon laboratory examination, hype IL-6 syndromes show elevation of the CRP level, polyclonal hyper gamma-globulinemia, anemia, and hypoalbuminemia. These findings are quite different from IgG4-related disease, which is not characterized by elevated serum IgA, IgM, and CRP levels. Therefore, laboratory findings are crucial for the differential diagnosis.

Association Between IgA Immunoglobulin Level and Response to Treatment for Immune Thrombocytopenia (ITP).

Abstract 3503 Poster Board III-440 Background ITP is a disorder of antibody mediated destruction and inhibition of production of platelets. ITP is idiopathic as it is unclear what immune factors relate to disease severity and response to treatment. We hypothesize that immune dysregulation represented by abnormal immunoglobulins especially elevated IgA may increase the risk of disease or failure to respond to treatment. Methods We performed a retrospective analysis of the Platelet Disorder Center master list, encompassing all of the patients with ITP seen at the Platelet Disorder Center in the past 10 years. The data includes demographics, use of and response to treatments, and certain selected laboratory values including levels of gamma globulins. The subject's serum IgA levels were observed for differences in response to treatment; IgG was not evaluated because of the use of IVIG. The analysis was performed using STATA statistical software and the Chi squared test. Results In total, data was available for 946 subjects with ITP of which 778 had baseline immunoglobulin data. The population was predominantly female (62%) and young with a mean age of 33.4 (SD 23.1) and ranged from less than 1 year old to 94 years of age. IgA mean was 188mg/dl (SD 136). 109 subjects (14%) had an elevated IgA (normal range 70-312). Subjects with an IgA greater than 312 were older than the general population with a mean age 48 (SD 19.4). Subjects with an IgA level greater than mean had a significantly increased chance of failing to respond to standard treatment (steroids, Win-Rho or IVIG) than patients with an IgA level lower than mean (13% vs. 8% p=0.05) and a trend towards failure to respond to individual treatments (rituxan 46% vs. 38% p =0.193, Win-Rho 27% vs. 21% p =0.25, IVIG 24% vs. 16% p= 0.07). In contrast patients with an IgA greater than mean were more likely to respond to splenectomy than patients with IgA less than mean (32.1% vs. 18.1% p=0.045). Subjects with an IgA greater than mean also had an increased risk of having a major bleed (9% vs. 6% p = 0.037). There was no difference in response to standard treatment in subjects with IgA below the lower limit of normal (70mg/dl) relative to subjects with a normal or elevated IgA (8% vs. 11% p= 0.69). Subjects with an IgA above the upper limit of normal (312mg/dl) did not have a significant increase in their chance to fail standard treatment relative to the rest of the study population (9% vs. 11% p =0.12). Subjects older than 65 were more likely to fail to respond to standard treatment than patients under 65 (20% vs. 8% p =0.01) and have an elevated IgA (20% vs. 13% p =0.034). Subjects older than 65 had a non-significant increase in risk of failure to respond to treatment if IgA was greater than mean (26% vs. 14% p= 0.16). This trend was less pronounced in subjects under 65 (10% vs. 7% p =0.19). Of the 6 patients with known inflammatory bowel disease (IBD), 5 had an IgA greater than mean (mean 255, range 193-395) and one had an undetectable IgA. However of the 30 patients treated for H.pylori the mean IgA level was similar to the general population (mean 188, range 8-498). Discussion More than 10% of patients with ITP have an elevated serum IgA. Subjects with IgA above mean are less likely to respond to standard treatment but more likely to respond to a splenectomy and more likely to have a major bleed than patients with an IgA below mean. This trend is more pronounced in elderly patients but was also suggested in patients younger than 65. However, those subjects with the highest IgA levels did not have a significantly increased risk of failing to respond to standard treatment and significant elevations in IgA were not obviously related to mucosal inflammation. Minor elevations in serum IgA may represent an inflammatory state not addressed with standard treatments for ITP. Further investigation into the role of IgA in the pathology of refractory ITP is warranted. Disclosures: Bussel: Sysmex: Research Funding; Eisai, Inc: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Immunomedics: Research Funding; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; Scienta: Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees.

Rapid deposition of glomerular IgA in BALB/c mice by nivalenol and its modifying effect on high IgA strain (HIGA) mice

To clarify the underlying mechanisms of IgA nephropathy (IgAN) induced by nivalenol (NIV), a trichothecene mycotoxin, we examined the time and dose relationships of glomerular deposition of IgA by NIV in BALB/c mice (Experiment 1), and also evaluated the modification of NIV on spontaneous IgAN in an inbred murine model, a high IgA strain (HIGA), during its early stage of pathogenesis (Experiment 2). In Experiment 1, female BALB/c mice were given a diet containing 0, 12, or 24 ppm concentration of NIV for 4 or 8 weeks. An increase in serum IgA levels was found at 24 ppm from 4 weeks. At week 8 of treatment, dose-dependent increases in serum IgA levels and glomerular deposition of IgA and IgG were observed without accompanying histopathological glomerular changes. On the other hand, in Experiment 2, control HIGA mice exhibited rather high levels of serum IgA as compared with BALB/c mice from 4 weeks of experiment as well as glomerular deposition of IgA and IgG and mesangial proliferation as revealed at week 8. NIV at 24 ppm further increased serum IgA in this strain; however, it did not enhance glomerular immunoglobulin deposition or histopathological lesion. These results suggest that NIV-induced increase of serum IgA levels may be primarily responsible for glomerular immunoglobulin deposition; however, NIV does not enhance glomerular IgA deposition that may lead to exacerbation of predisposed IgAN in the short term, irrespective of the further elevation of serum IgA from the high basal levels.

Clinical impact of altered immunoglobulin levels in Henoch–Schönlein purpura

The aim of the present study was the identification of immunological features, present at the time of diagnosis, that would predict the severity of Henoch-Schönlein purpura and its outcome. A cohort study was carried out in a tertiary pediatric hospital of 69 children with Henoch-Schönlein purpura, in whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly determined. During the acute phase of the disease in 54/69 patients (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain complications involving the kidneys and the gastrointestinal tract were noted as opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69 children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed renal involvement while only 1/19 children (5.3%) with normal IgA concentration had renal involvement. Considering separately the group of 9/69 children (13%) with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective of IgA and IgG concentration, we found a comparable percentage of children who had both renal and intestinal involvement without, however, developing severe complications, which were exclusively seen in patients with increased IgA (5/7 children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children (37.7%) and in 73% of cases it was associated with increased serum IgA values. Renal involvement was seen in 32% of children with increased IgA values. Most importantly, elevated IgA concentration along with reduced IgM levels was associated with higher prevalence of severe complications.

Gluten sensitivity in patients with IgA nephropathy

Coeliac disease is more frequent in IgA nephropathy (IgAN) patients compared to the healthy population. Several hypotheses postulate that food antigens like gluten may be involved in the onset of IgAN. In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies. Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed. It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

Lymphotoxin alpha LTA+496C allele is a risk factor for periodontitis in patients with coronary artery disease

Periodontitis and coronary artery disease (CAD) are inflammatory diseases and associated with each other. The major histocompatibility complex (MHC) region carries genes involved in immune response and inflammation. We investigated whether the MHC genes correlate with the presence of periodontitis or with the occurrence of periodontal pathogens in patients with CAD. Blood and saliva samples from CAD patients (n = 106) were collected at the time of hospitalization. Nine MHC genetic markers [human leukocyte antigen (HLA)-A, HLA-B, HLA-DRB1, lymphotoxin alpha (LTA) +253(a/g), +496(C/T), +633(c/g), +724(C/A), C4A and C4B)] were typed. Based on panoramic tomography, patients were categorized into nonperiodontitis and periodontitis groups. Two major periodontal pathogens, Aggregatibacter (Actinobacillus) actinomycetemcomitans and Porphyromonas gingivalis, were cultivated and polymerase chain reaction-amplified from salivary samples. Serum immunoglobulin (Ig)A and IgG antibody levels to these pathogens were measured. In the univariate analysis, LTA+496C allele (OR = 5.29; 95% CI = 2.07-13.51, P = 0.00027), and the occurrence of P. gingivalis in saliva (OR = 4.74; 95% CI = 1.64-13.70; P = 0.002) were more frequent in periodontitis when compared with nonperiodontitis. Similarly, serum IgA antibody level against the pathogen was increased in periodontitis (P = 0.048). In the multiple logistic regression analysis, when a wide range of covariates was included, the LTA+496C allele (OR = 10.87; 95% CI = 3.23-36.60; P = 0.00012) and the elevated serum IgA antibody level against P. gingivalis (OR = 1.56; 95% CI = 1.05-2.30; P = 0.026) remained as significant risk factors for periodontitis. In conclusion, the major finding of this study is that the LTA+496C allele is associated with periodontitis in patients with CAD.

Dose-Dependent Effects of T-2 Toxin on Performance, Lipid Peroxidation, and Genotoxicity in Broiler Chickens

The objective of the present study was to evaluate the effects of different concentrations of T-2 toxin in feed on performance, lipid peroxidation, and genotoxicity in vivo. For a 17-d period, T-2 toxin was added to the diet of the chickens. Fifty 22-d-old male broiler chickens were divided into 5 groups that were supplemented with different concentrations of T-2 toxin: control (0.0 mg/kg of feed), T 0.5 (0.5 mg/kg of feed), T 1.5 (1.5 mg/kg of feed), T 4.5 (4.5 mg/kg of feed), and T 13.5 (13.5 mg/kg of feed). Deoxyribonucleic acid fragmentation in spleen leukocytes, malondialdehyde in plasma and liver, total plasma antioxidative status, glutathione peroxidase activity, and total serum Ig (IgA and IgG) were measured. Feed consumption and BW gain decreased when the concentration of T-2 toxin was 4.5 and 13.5 mg/kg of feed. Compared with the control group, the rate of DNA damage increased significantly in the group fed 13.5 mg of T-2 toxin/kg of feed. In contrast to DNA fragmentation, indicators of oxidative stress did not show differences between groups fed T-2 toxin and the control. More serum IgA was detected in the group T 13.5 compared with the control, whereas there were no differences in serum IgG levels. The results of the present study indicate that impaired performance, DNA fragmentation in spleen leukocytes, and elevated serum IgA levels induced by T-2 toxin are dose-dependent. Based on our results, we could not confirm the hypothesis that oxidative stress is among the mechanisms by which T-2 toxin induces DNA fragmentation.

Increased Prevalence of Anti-Gliadin IgA-Antibodies with Aberrant Duodenal Histopathological Findings in Patients with IgA-Nephropathy and Related Disorders

Background: Antibodies present in coeliac disease may occur in IgA-nephropathy. This raises the question of food intolerance in the disease. Evidence for a true correlation between the two disorders has however been scarce.Design: Sera from 89 patients with IgA-nephropathy and 13 other patients with IgA deposits in the glomeruli of kidney biopsies were analysed for IgA-antibodies to gliadin, endomysium and tissue transglutaminase (92/102 patients).Results: Eleven out of 89 (12.4%) of the patients with IgA-nephropathy and five of the 13 others (38%) had elevated titres of IgA-antibodies to gliadin but, in all cases but one, normal IgA-antibodies to endomysium. Patients with IgA-nephropathy and elevated IgA-antibodies to gliadin had elevated total serum IgA more frequently than patients who had not (p<0.01). Two patients with IgA-nephropathy and one with Hennoch Schönlein's purpura had elevated IgA-antibodies to tissue transglutaminase.Small bowel biopsy in 7 out of 11 IgA-antibodies to gliadin positive patients with IgA-nephropathy was pathologic in three cases (two with Marsh I). One patient with chronic glomerulnephritis also had Marsh I.Conclusions: We found no increased frequency of verified coeliac disease in 89 patients with IgA-nephropathy. Two patients with IgA-nephropathy and one patient with chronic glomerulonephritis with IgA deposits in the kidney biopsy had a Marsh I histopathology. The findings suggest a possible link of celiac disease to IgA-nephropathy and a role for antibodies to food antigens in this disorder.

SEROLOGICAL ANALYSES OF UNAFFECTED PRESUMED GENE CARRIERS OF CELIAC DISEASE

Celiac disease (CD) is known to be familial but its inheritance pattern is not fully understood. Serologic tests are used to identify at risk individuals in CD families. We defined presumed gene carriers for celiac disease as individuals testing negative for IgA endomysial antibody, who have both a CD affected parent, sibling or cousin and a CD affected child. We hypothesized that presumed CD gene carriers would have unique serological profiles. Methods: We measured and compared IgG and IgA tissue transglutaminase (tTG), endomysial antibody (EMA) antigliadin antibody (GA) and total serum IgA in presumed gene carriers, HLA DQ2+ organ donors, and Red Cross blood donors. Results: There were no significant differences in EMA, GA, or IgA tTG levels in controls and presumed carriers. Presumed gene carriers had significantly elevated total serum IgA levels compared to DQ2 and blood donor controls (Table 1). The levels of IgG tTG were also significantly above those of the controls (Table 2).TABLE 1: Serum IgA Levels (mg/dL)TABLE 2: IgG tTG levelsConclusion: Higher total serum IgA levels in CD family members who are presumed gene carriers could be an indication of an accelerated mucosal immune response. The increased IgG tTG levels, indicates a slight tendency towards an immune response to transglutaminase antigen. However, the data clearly indicate that no test is clinically useful in differentiating presumed gene carriers from controls and there does not appear to be a unique serologic pattern differentiating the presumed gene carrier family member.

IgA Nephropathy

IgA Nephropathy

IgA levels are predictors of mortality in Finnish nonagenarians

It has been demonstrated that in obviously healthy, very old people increased levels of inflammatory markers as well as some defects in T lymphocyte populations are strong predictors of mortality. Very little is known about the role of possible functional defects in antibody formation. To examine this, we now measured IgM, IgG and IgA concentrations in a cohort of 285 nonagenarians (67 males, 218 females). IgG and IgA levels were significantly higher than those of healthy middle-aged controls. The analyzed serum samples were taken at the age of 90–91 years. After 4 years, 20 males and 94 females had survived. To analyze the role in predicting mortality, the immunoglobulin data (as well as the measured CRP and IL-6 concentrations) were stratified according to this survival data. IgA levels (and CRP and IL-6 levels) were clearly higher in the nonsurvivors than in the survivors. These data imply that elevated serum IgA level, i.e. indicator of intestinal inflammation and/or defect in mucosal defence, is a strong mortality predicting factor.

Urticarial Erythema Associated with IgA Myeloma

We report a case of atypical urticaria associated with IgA multiple myeloma. A 79-year-old man presented with a two-month history of wheal-like erythema, which lasted approximately one week without any response to anti-histamines. Histological examination of a lesion revealed leukocytoclasia as well as perivascular leukocytic infiltration, being consistent with urticarial erythema. Laboratory investigation showed markedly elevated serum IgA concentration and M-protein in serum protein electrophoresis. A bone marrow examination led to a diagnosis of myeloma. An immunofluorescence study failed to detect any IgA deposit in the lesion. However, the wheal-like eruptions disappeared when the IgA myeloma was treated and reappeared when it relapsed. We conclude that this long lasting urticaria was the cutaneous manifestation of IgA myeloma.

Dysregulated LIGHT expression on T cells mediates intestinal inflammation and contributes to IgA nephropathy.

Whether and how T cells contribute to the pathogenesis of immunoglobulin A nephropathy (IgAN) has not been well defined. Here, we explore a murine model that spontaneously develops T cell-mediated intestinal inflammation accompanied by pathological features similar to those of human IgAN. Intestinal inflammation mediated by LIGHT, a ligand for lymphotoxin beta receptor (LTbetaR), not only stimulates IgA overproduction in the gut but also results in defective IgA transportation into the gut lumen, causing a dramatic increase in serum polymeric IgA. Engagement of LTbetaR by LIGHT is essential for both intestinal inflammation and hyperserum IgA syndrome in our LIGHT transgenic model. Impressively, the majority of patients with inflammatory bowel disease showed increased IgA-producing cells in the gut, elevated serum IgA levels, and severe hematuria, a hallmark of IgAN. These observations indicate the critical contributions of dysregulated LIGHT expression and intestinal inflammation to the pathogenesis of IgAN.

Effects of tumor necrosis factor type 1 and 2 receptor deficiencies on anorexia, growth and IgA dysregulation in mice exposed to the trichothecene vomitoxin

Dietary exposure of mice to vomitoxin (VT), a trichothecene mycotoxin, causes anorexia and impaired growth as well as inducing elevated serum IgA and kidney mesangial IgA deposition in a manner analogous to human IgA nephropathy. Based on the observations that TNF-α is induced by in vitro and in vivo VT exposure, it was hypothesized that this cytokine plays a role in the nutritional and immunological effects of this toxin. To test this hypothesis, the effects of dietary VT on feed intake, weight gain, serum IgA levels and kidney mesangial IgA deposition in mice homozygous for targeted disruption of the two known TNF-α cell surface receptors, TNFR1(p55) or TNFR2(p75), were compared to effects in corresponding C57BL/6J wild-type (WT) mice with normal receptor function. The capacity of VT to cause feed refusal or impair weight gain over a 12-week feeding period was not impaired in TNFR1 knockout (KO) or TNFR2-KO as compared to WT mice. Both WT and TNFR-KO mice fed VT exhibited reduced ( P<0.05) feed conversion efficiency, but surprisingly, feed conversion efficiency was significantly higher ( P<0.05) in TNFR1-KO and TNFR2-KO fed either control or VT diets than in corresponding WT mice. By week 12, serum IgA concentrations in all three mouse groups fed VT were significantly higher than those for corresponding mice fed control diets ( P<0.05). Serum IgA levels in the VT-fed TNFR1-KO group were significantly less ( P<0.05) than those for the VT-fed WT mice at 4, 8 and 12 weeks, whereas no differences in this parameter were found between the TNFR2-KO and WT groups. Serum IgA immune complex concentrations were measured at wk 12 and found to follow an identical pattern to IgA. Kidneys taken from VT-fed TNFR2-KO and WT mice after 12 weeks had significantly increased mesangial IgA deposition as compared to controls. While slight increases in mesangial IgA were also observed in VT-fed TNFR1-KO mice, these levels were significantly less ( P<0.05) than that found in VT-fed TNFR2-KO and WT mice. Taken together, the data suggest that while VT-mediated anorexic and growth effects were largely independent of TNF-α, VT-induced dysregulation of IgA production was dependent, in part, on the interaction of TNF-α with TNFR1.

Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouse.

The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2(Akita)), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes. This study aimed to investigate renal complications in the Akita mouse model, which has been maintained in a heterozygous state Ins2(Akita) (+/-) with a C57BL/6 background (B6). Renal function (BUN, creatinine), serum IgA concentrations and histological changes in the kidneys were evaluated in diabetic and control mice in a B6 background. Five each of male and female mice per group (diabetes vs. control) were killed at 10, 20, 30 and 40 weeks of age. The influence of major histocompatibility antigens (MHC) on renal complications was tested using male diabetic mice in a C3H/He (C3H) background. When compared with controls, diabetic males, but not females, developed impaired renal function with elevation of serum IgA after 30 weeks of age. Diabetic glomerulosclerosis advanced with age in both sexes. Diffuse granular mesangial deposits of IgA were detected by immunofluorescence microscopy in diabetic males after 20 weeks. We tested whether the IgA-associated lesions were influenced by MHC using diabetic males in a C3H background. Similar degrees of diabetic glomerulosclerosis and glomerular IgA deposition were found in mice with C3H and B6 backgrounds. Akita mouse is a unique mouse model showing both mesangial sclerosis and IgA nephropathy.

Serum Responses to the Combination of Epstein-Barr Virus Antigens in Patients With Nasopharyngeal Carcinoma in a Follow-up Study

Background. Elevated serum IgA to Epstein-Barr virus (EBV) antigens was frequently found in patients with nasopharyngeal carcinoma (NPC). Recent evidence indicated that EBV in NPC patients could be a mixture of latent and active infections. Methods. In this longitudinal study, we therefore used six EBV antigens from both latent and acute phases of infection to evaluate NPC patients. Immunosensitivity was determined using enzyme-linked immunosorbent assay, and immunospecificity was assessed using immunoblot. Results. Levels of serum IgA to EBV in NPC patients were significantly higher than the levels in the healthy control subjects. Persistent high IgA titer or the aberrant increase of IgA level indicated a high risk of disease recurrence and early distant metastasis. Conclusions. Disease progression of NPC was proceeded by the increase of IgA titer to EBV antigens. Measurement of serum IgA to a panel of EBV antigens from both latent and acute viral . infections could, therefore, provide a predictive index for NPC response.

Ｓｐｒａｇｕｅ‐Ｄａｗｌｅｙラットの免疫機能に及ぼす玄麦玄米酢摂食の効果

To clarify the immunoregulatory activity of Genbakugenmaisu, a vinegar product produced from brown wheat and rice, LTB4 releasing activity of peritoneal exudate cells isolated from Sprague-Dawley rats was examined in the presence of the vinegar and found that the vinegar suppressed LTB4 release of the cells. Then, Sprague-Dawley rats were allowed free access to the water containing the vinegar at the 0, 0.5, 1.0, or 2.0% level for 3 weeks. Although Genbakugenmaisu intake did not affect to LTB4 productivity of the PEC, it not only elevated serum IgA and IgM levels, but also enhanced IgA, IgG and IgM productivity of mesenteric lymph node lymphocytes of the rats. These results suggest that the vinegar enhance immune function of the rats through activation of immunoglobulin production.