Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice
| Autor: | Tony N. Marion, Meera R. Krishnan, Congmiao Wang |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Glomerular deposits
Lupus nephritis Antibody Affinity Immune complex formation urologic and male genital diseases Article immune complexes 03 medical and health sciences Mice 0302 clinical medicine systemic lupus erythematosus Glomerular Basement Membrane medicine Animals complement Complement Activation 030304 developmental biology 030203 arthritis & rheumatology Basement membrane 0303 health sciences Mice Inbred BALB C Hybridomas biology Chemistry urogenital system Glomerular basement membrane Antibodies Monoclonal DNA medicine.disease Molecular biology Lupus Nephritis Chromatin 3. Good health Complement system Disease Models Animal Proteinuria medicine.anatomical_structure Nephrology Antibodies Antinuclear Immunology Injections Intravenous biology.protein Binding Sites Antibody Antibody Nephritis Heparan Sulfate Proteoglycans |
| Zdroj: | Kidney international |
| ISSN: | 1523-1755 |
| Popis: | The strongest serological correlate for lupus nephritis is antibody to double-stranded DNA, although the mechanism by which anti-DNA antibodies initiate lupus nephritis is unresolved. Most recent reports indicate that anti-DNA must bind chromatin in the glomerular basement membrane or mesangial matrix to form glomerular deposits. Here we determined whether direct binding of anti-DNA antibody to glomerular basement membrane is critical to initiate glomerular binding of anti-DNA in experimental lupus nephritis. Mice were co-injected with IgG monoclonal antibodies or hybridomas with similar specificity for DNA and chromatin but different IgG subclass and different relative affinity for basement membrane. Only anti-DNA antibodies that bound basement membrane bound to glomeruli, activated complement, and induced proteinuria whether injected alone or co-injected with a non-basement-membrane–binding anti-DNA antibody. Basement membrane–binding anti-DNA antibodies co-localized with heparan sulfate proteoglycan in glomerular basement membrane and mesangial matrix but not with chromatin. Thus, direct binding of anti-DNA antibody to antigens in the glomerular basement membrane or mesangial matrix may be critical to initiate glomerular inflammation. This may accelerate and exacerbate glomerular immune complex formation in human and murine lupus nephritis. |
| Databáze: | OpenAIRE |
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