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Lack of effect of a single injection of human C‐reactive protein on murine lupus or nephrotoxic nephritis
Author(s) -
Carlucci Francesco,
Terence Cook H.,
Garg Abhilok,
Pepys Mark B.,
Botto Marina
Publication year - 2010
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.27232
Subject(s) - lupus nephritis , proteinuria , autoantibody , serum amyloid p component , medicine , nephritis , immunology , systemic lupus erythematosus , antibody , immune complex , glomerular basement membrane , immune system , kidney , c reactive protein , disease , endocrinology , inflammation
Objective It has been reported that a single dose of human C‐reactive protein (CRP) can prevent and reverse the renal damage in murine models of spontaneous lupus, as well as the rapid‐onset immune complex disease induced in the accelerated nephrotoxic nephritis (ANTN) model. This study was undertaken to attempt to replicate these observations using a highly purified and fully characterized human CRP preparation. Methods (NZB × NZW)F 1 (NZB/NZW) mice were treated with a single 200‐μg subcutaneous injection of CRP or control reagents either before disease onset at 4 months of age or when high‐grade proteinuria was present at 7 months of age. Mice were monitored at least monthly for proteinuria and autoantibody levels. ANTN was induced by preimmunizing C57BL/6 mice with sheep IgG, followed 5 days later by injection of sheep anti‐mouse glomerular basement membrane antibody and CRP or control reagents. Renal disease was assessed by regular urinalysis and histologic evaluation. Results CRP treatment of NZB/NZW mice, either early or late in the disease, had no effect on proteinuria, autoantibody titers, or survival. CRP administration did not reduce renal injury or alter disease in the ANTN model. Human serum amyloid P component, a pentraxin protein that is very closely related to CRP, similarly had no effect. Conclusion Our completely negative observations do not confirm that human CRP has reproducible antiinflammatory or immunomodulatory effects in these murine models, nor do they support the suggestion that CRP might be useful for therapy of lupus or immune complex–mediated nephritis.

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