Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose: The pattern recognition molecules C-reactive protein (CRP) and complement protein 1q (C1q) are pivotal parts of the innate immune system and display relevant biological functions in the pathogenesis of systemic lupus erythematosus (SLE). Circulating autoantibodies directed against CRP and C1q are frequently found in SLE patients with active disease, especially those with lupus nephritis, and raised serum autoantibody levels reportedly relate to both disease activity and prognosis. This study was performed to assess glomerular localization of IgG, CRP and C1q as a reflection of nephritogenic immune complexes (ICs) in patients with active diffuse proliferative lupus nephritis.
Methods: Renal specimens from five well-characterized patients with active diffuse proliferative lupus nephritis were examined by immunogold electron microscopy to pinpoint glomerular localization of CRP, C1q, C3c and double-stranded (ds) DNA in relation to IgG. Renal biopsies from patients with Henoch-Schönleins purpura, pauci-immune nephritis and renal cancer served as controls. In addition, serum IgG class antibodies against CRP, C1q, and nucleosomes were analyzed by ELISA in the lupus nephritis patients before, during and after renal flares. Informed consent was obtained from all subjects and the research protocol was approved by the Regional Ethics Committee in Lund (H4 207/2005).
Results: Tissue CRP, C1q, C3c and dsDNA were found to co-localize with IgG in renal subendothelial electron dense deposits. Disease controls only showed negligible staining for the tissue markers as compared with lupus nephritis and none had detectable anti-C1q, anti-CRP or anti-nucleosome antibodies. All SLE patients had circulating anti-nucleosome antibodies, and four of five were anti-CRP, anti-dsDNA, and anti-C1q antibody positive at the time of biopsy/flare. Using accumulated data (pre–post nephritis), one could observe that anti-nucleosome and anti-C1q antibody levels were more interrelated (r=0.42, p=0.046) than were the levels of anti-CRP versus anti-C1q or anti-nucleosome antibodies, respectively.
Conclusion: The results support the notion of a pathogenic role not only for antibodies directed against dsDNA, but also for anti-CRP and anti-C1q in lupus nephritis. The glomerular ICs may have been generated by deposition of circulating ICs or by in situ IC formation. The demonstrated correlation between anti-C1q and anti-nucleosome antibodies, but not between these autoantibodies and anti-CRP, indicate that the latter may reflect an independent role in the pathogenesis of lupus nephritis.
Disclosure:
C. Sjöwall,
None;
A. I. Olin,
None;
T. Skogh,
None;
J. Wetterö,
None;
M. Mörgelin,
None;
O. Nived,
None;
G. Sturfelt,
None;
A. A. Bengtsson,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/co-localization-of-c-reactive-protein-immunoglobulin-g-and-complement-in-renal-subendothelial-immune-deposits-of-proliferative-lupus-nephritis-detected-using-immunogold-electron-microscopy/