Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice

Meera R. Krishnan, Congmiao Wang, Tony Marion

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)184-192
Number of pages9
JournalKidney International
Volume82
Issue number2
DOIs
StatePublished - Jul 2 2012

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Glomerular Basement Membrane
Lupus Nephritis
Antinuclear Antibodies
Autoantibodies
DNA
Basement Membrane
Chromatin
Immunoglobulin G
Heparan Sulfate Proteoglycans
Hybridomas
Antigen-Antibody Complex
Proteinuria
Monoclonal Antibodies
Inflammation
Antigens
Membranes
Antibodies

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Anti-DNA autoantibodies initiate experimental lupus nephritis by binding directly to the glomerular basement membrane in mice. / Krishnan, Meera R.; Wang, Congmiao; Marion, Tony.

In: Kidney International, Vol. 82, No. 2, 02.07.2012, p. 184-192.

Research output: Contribution to journalArticle

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