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Differential expression of laminin chains and anti‐laminin autoantibodies in experimental lupus nephritis
Author(s) -
PeutzKootstra Carine J.,
Hansen Kim,
De Heer Emile,
Abrass Christine K.,
Bruijn Jan A.
Publication year - 2000
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/1096-9896(2000)9999:9999<::aid-path707>3.0.co;2-l
Subject(s) - laminin , filamin , autoantibody , lupus nephritis , glomerulonephritis , immunology , biology , antibody , medicine , endocrinology , pathology , extracellular matrix , microbiology and biotechnology , kidney , disease , cell , biochemistry , cytoskeleton
Mice with chronic graft‐versus‐host disease (GvHD) develop a lupus‐like disease with severe immune complex glomerulonephritis. Previous studies with this model have shown that anti‐laminin autoantibodies are involved in immune complex formation and that glomerular laminin expression alters qualitatively. The present study investigated glomerular laminin chain expression and autoantibody reactivity with matrix antigens during disease development in mice with chronic GvHD, killed before and 6, 8, 10, and 11 weeks after disease induction, using antibodies raised against laminin chain peptides, in immunofluorescence and western blotting studies. Decreased glomerular expression of the laminin β1 chain, unaltered expression of the laminin β2 and γ1 chains, and increased expression of the laminin α1 chain and filamin/actin‐binding protein 280 (ABP 280) were found during disease progression. Furthermore, 4 weeks after disease induction, autoantibodies appeared which were reactive with laminin α1, β1, β2, and γ1 chains, and filamin in rat mesangial cell matrix. Ten weeks after disease induction, autoantibodies reacted with filamin, and β2 and γ1 laminin chains. Autoantibodies reacted with laminin chains only and not with other proteins in matrices extracted from glomeruli of normal and diseased mice. Staining with H50, an anti‐laminin α1 chain/anti‐filamin monoclonal autoantibody derived from an MRL/lpr mouse with spontaneous lupus nephritis, confirmed these observations and showed identical anti‐laminin/anti‐filamin autoantibody reactivity in two different models for lupus nephritis. In summary, differential glomerular expression of laminin chains was found during the development of chronic GvHD. Concomitantly with expression of the laminin α1 chain and/or filamin in the glomerulus, anti‐laminin α1 and/or anti‐filamin reactivity was present, pointing towards a role for (neo) antigen expression in the epitope spreading of the immune response. Furthermore, glomerular expression of laminin β1 decreased in conjunction with decreased presence of anti‐laminin β1 reactivity, presumably due to antigen masking or shedding of immune complexes into the urine. These changes in anti‐laminin chain autoantibodies, with concomitant alterations in the glomerular expression of laminin chains, may aggravate progressive immune injury in this model for lupus nephritis. Copyright © 2000 John Wiley & Sons, Ltd.