ovalbumin and Glomerulonephritis--IGA

We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli.

Topics: Animals; B-Lymphocytes; Cell Proliferation; Cholera Toxin; GATA3 Transcription Factor; Gene Expression; Glomerulonephritis, IGA; Immune Tolerance; Immunization; Immunoglobulin A; Interleukin-5; Mannose-Binding Lectin; Mesangial Cells; Mice; Mice, Transgenic; Ovalbumin; Peyer's Patches; Primary Cell Culture; Spleen; T-Lymphocytes, Regulatory; Th1 Cells; Th2 Cells

IgA nephropathy (IgAN) is a form of immune complex glomerulonephritis that occurs spontaneously in humans. This unit describes the induction of active disease in inbred mice, utilizing inert proteins or a common viral pathogen as the inciting antigen. An alternate protocol is offered for the induction of disease in rats by noninfectious protein antigens. Support protocols are presented for the evaluation of the extent of disease, for preparation of infectious and inactivated suspensions of viral stock, and for quantification of the virus.

Topics: Administration, Oral; Animals; Apoferritins; Cattle; Chickens; Disease Models, Animal; Female; gamma-Globulins; Glomerulonephritis, IGA; Horses; Humans; Injections; Mice; Mice, Inbred BALB C; Mice, Inbred C3H; Ovalbumin; Rats; Rats, Inbred Lew; Rats, Wistar; Sendai virus; Serum Albumin

It has been postulated that IgA NP is caused by mesangial deposition of IgA-containing immune complexes formed by IgA polymers (pIgA) which are overproduced in response to antigens presented at mucosal surfaces. The intestinal mucosa is one possible source of this pIgA. To test whether antibodies to dietary antigens might be involved in the pathogenesis of IgA NP, we measured IgG and IgA serum antibody activities to gluten, a gluten fraction called glyc-gli, alpha-lactalbumin, beta-lactoglobulin, casein and ovalbumin in 54 patients with IgA NP by an enzyme-linked immunosorbent assay (ELISA). The IgA activities to gluten antigens and alpha-lactalbumin were significantly increased in IgA NP compared with a group of 40 age-matched healthy controls. In a previous study we found that 4 out of 12 patients with IgA NP and gastrointestinal complaints had subtotal villous atrophy; this indicated that many patients with IgA NP have altered intestinal permeability which may lead to activation of their intestinal immune system. Taken together our results showed a relation between the intestinal humoral immune system and IgA NP and indicated that antibodies to dietary antigens in some patients may be directly involved in the pathogenesis of IgA NP.

Topics: Adult; Antibodies; Antigen-Antibody Complex; Caseins; Dietary Proteins; Enzyme-Linked Immunosorbent Assay; Female; Glomerulonephritis, IGA; Glutens; Humans; Intestinal Absorption; Intestinal Mucosa; Lactalbumin; Lactoglobulins; Male; Ovalbumin

In IgA glomerulonephritis (GN), the pathogenic role of IgA is well documented, but the specificity of these IgA is unknown. Cases of celiac disease associated with IgA GN have been reported and led us to investigate the role of gliadin sensitivity. We measured IgA, IgG and IgM antibodies to gliadin, beta-lactoglobulin and ovalbumin by ELISA (results expressed as optical density; OD) in 27 patients with primary IgA GN, 14 with membranous GN (MGN), 21 with idiopathic nephrotic syndrome (INS) and 21 healthy controls. The normal value for antigliadin IgA was less than 0.650 OD. 19/27 patients with IgA GN had a raised level versus 2/14 in MGN and 2/21 INS (p less than 0.001: IgA GN vs. MGN, INS and controls). Antibodies to beta-lactoglobulin were rarely found and were not more frequent in IgA GN. Cross-reactivity with reticulin was investigated in 16 patients who were serum-positive for IgA antigliadin: no reticulin antibodies were detected by immunofluorescence. Antigliadin IgA are of diagnostic value for distinguishing IgA GN from other GN, with a sensitivity of 70%, a specificity of 89%, a positive predictive value of 83% and a negative one of 79%.

Topics: Adult; Antibody Specificity; Celiac Disease; Dietary Proteins; Enzyme-Linked Immunosorbent Assay; Female; Food Hypersensitivity; Gliadin; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Lactoglobulins; Male; Ovalbumin; Plant Proteins

An IgA nephropathy model based on long-term oral administration of protein antigens was evaluated in three mouse strains using trinitrophenyl (TNP)-conjugated ovalbumin. Administration of the antigen for 14 weeks did not induce a significant IgA response nor deposition of IgA in the mesangium in any of the mouse strains. If, however, serum IgA anti-TNP antibodies were induced by intraperitoneal injection of anti-TNP producing MOPC-315 tumor cells, subsequent intravenous injection of antigen resulted in the deposition of IgA immune complexes in the mouse kidneys. Hematuria did not occur. In conclusion, previous data showing that long-term oral administration of protein antigens induces mesangial IgA deposits could not be confirmed with TNP ovalbumin. However, mesangial IgA deposits were obtained in animals treated with MOPC-315 tumor cells as described by Rifai et al. [J. exp. Med. 150: 1161-1173, 1979].

Topics: Animals; Antibody Formation; Female; Glomerular Mesangium; Glomerulonephritis, IGA; Mice; Mice, Inbred Strains; Ovalbumin

Topics: Antibody Specificity; Antigen-Antibody Complex; Diet; Glomerulonephritis, IGA; Hematuria; Humans; Immunoglobulin A; Ovalbumin; Serum Albumin, Bovine