Antimouse Laminin Antibodies in IgA Nephropathy and Various Glomerular Diseases

Abstract

IgG, IgA and IgM class antibodies to mouse laminin and human fibronectin in sera from patients with various glomerular diseases (50 cases of IgA nephropathy, 5 cases of minimal-change nephrotic syndrome; 6 cases of membranous nephropathy, 5 cases of systemic lupus erythematosus, 2 cases of Henoch-Schönlein purpura, 3 cases of poststreptococcal nephritis and 4 cases of preeclampsia) and from 30 normal controls were tested using a solid-phase enzyme-linked immunosorbent assay method. IgA antimouse laminin antibody titers in sera from IgA nephropathy patients were significantly higher (p < 0.05) than in controls. There were no statistical differences in IgA antimouse laminin antibody titers between patients with other glomerular diseases and normal controls. IgM antimouse laminin antibody was significantly raised (p < 0.01) in sera from patients with preeclampsia. The reaction of mouse laminin with the IgA nephropathy and preeclampsia sera on each of the IgA and IgM assay systems was inhibited by the antigen at up to 5 μg/ml. However, it was not inhibited by anti-C3d, anti-C1q, anti-J chain and antisecretory component sera or saccharides. The reaction of mouse laminin with an exceptionally high-titer IgA antimouse laminin antibody serum from a normal control on the IgA assay system was clearly inhibited by 1 mMof melibiose, which contains α-galactosyl residues. The same concentration of melibiose, however, did not inhibit the reaction of mouse laminin with IgA nephropathy sera on the same assay system. Treatment of mouse laminin with α-galactosidase did not alter any binding from IgA nephropathy sera but binding was lost from an exceptionally high-titer normal control serum. There were no correlations between serum IgA level and IgA antimouse laminin antibody titer in sera from IgA nephropathy patients. Immunoblot techniques revealed the presence of antibody in sera from IgA nephropathy patients reacting with both subunits A and B of laminin, somewhat stronger with laminin A. None of the sera tested contained antifibronectin antibodies. These results indicate that the IgA antimouse laminin antibody is a specific antibody in IgA nephropathy and might play a role in the pathogenesis of the nephritis since mouse laminin and human mesangial laminin present a common epitope.

Antilymphocyte Antibodies against CD4+CD45R + Subsets in Patients with IgA Nephropathy

“…35] and soybean protein by us [36,37]. 400 Sato/Kino/Naheshima/Koshikawa Anti-CD4-t-CD45R + in IgA Nephropathy Autoimmune reactions are also considered as one of the important factors in the pathogenesis of IgA N. Various types of autoantibodies have been recognized, such as cold reacting antinuclear factor [9], antimouse laminin IgA anti body [10]. IgA rheumatoid factor [II], antivascular endothel ial cells [12], anticollagen IgA antibodies [13], Also, it has been reported that some autoimmune diseases or phenome na, i.e., scleritis [38], rheumatoid arthritis [39], sicca syn drome [40], are associated with IgA N. Moreover, it has been claimed that corticosteroids are effective in the treat ment of IgA N [41], This evidence indicates that autoim mune mechanisms participate strongly in the pathogenesis of IgA N. In this study, the presence of antilymphocyte antibodies against CD4 + CD45R+ cells is described in sera of patients with IgA N. CD45R (2H4) antibody subdivides the CD4-I-popula tion into suppressor/inducer(CD44-CD45R + )and helper/inducer (CD4 + CD45R-) subsets [15,16].…”

“…Moreover, various kinds of autoantibodies have been recognized in sera of patients with IgA N, such as cold reacting antinuclear factor [9], antimouse lam inin IgA antibodies [10], IgA rheumatoid factor [II], antivascular endothelial cells [12] and anticollagen IgA antibodies [13], and complexes containing IgA and fibronectin [14]. These abnormalities may participate strongly in the patho genesis a n d /o r the progression of IgA N.…”

Human anti-fibronectin antibodies in systemic lupus erythematosus: occurrence and antigenic specificity

“…However, these workers did limited studies on the specificity of the antibodies, and none has localized the binding site for the antibodies within the multi-domain Fn molecule. By contrast, a study investigating antibodies to ECM in patients with SLE nephritis failed to detect anti-Fn antibodies [19]. [n viewof limited and variable data on antibodies to Fn and the rnany varied biological Tunctions oi" this ECM protein, we investigated the occurrence and specificity ofanti-Fn antibodies in sera of patients with SLE.…”

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

“…70 These results indicate that alteration of the IgA-FcaRI interaction may play a key role in the development of IgAN. The third mechanism for the formation of IgA complexes in IgAN may involve IgA binding to other circulating proteins such as fibronectin, collagen or laminin, [72][73][74] suggesting an additional mechanism by which IgA complexes bind to mesangium through adhesion to extracellular matrix proteins. In favor of this hypothesis, knockout mice for uteroglobin, a serum protein that controls fibronectin levels, develop IgAN.…”