Autoantibodies against C-Reactive Protein Influence Complement Activation and Clinical Course in Lupus Nephritis

Autoantibodies against the major acute-phase reactant C-reactive protein (CRP) are frequently found in patients with lupus nephritis. Further defining the autoimmune epitopes on CRP may not only improve patient stratification but also, hint at mechanisms of CRP action. Herein, we show that amino aci...

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Bibliographic Details
Published in:Journal of the American Society of Nephrology 2017-10, Vol.28 (10), p.3044-3054
Main Authors: Li, Qiu-Yu, Li, Hai-Yun, Fu, Ge, Yu, Feng, Wu, Yi, Zhao, Ming-Hui
Format: Article
Language:English
Subjects:
Adolescent
Adult
Autoantibodies - metabolism
C-Reactive Protein - immunology
C-Reactive Protein - metabolism
Case-Control Studies
Clinical Research
Complement Factor H - metabolism
Epitope Mapping
Female
Humans
Lupus Nephritis - diagnosis
Lupus Nephritis - immunology
Male
Prognosis
Young Adult
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Summary:Autoantibodies against the major acute-phase reactant C-reactive protein (CRP) are frequently found in patients with lupus nephritis. Further defining the autoimmune epitopes on CRP may not only improve patient stratification but also, hint at mechanisms of CRP action. Herein, we show that amino acids 35-47 constitute the major epitope recognized by anti-CRP autoantibodies in patients with lupus nephritis. Notably, the presence of autoantibodies against amino acids 35-47 associated with more severe renal damage and predicted worse outcome. This epitope is exposed on CRP only after irreversible structure changes, yielding a conformationally altered form termed modified or monomeric CRP (mCRP). ELISA and surface plasmon resonance assays showed that amino acids 35-47 mediate the interaction of mCRP with complement factor H, an inhibitor of alternative pathway activation, and this interaction greatly enhanced the cofactor activity of complement factor H. In contrast, autoantibodies against amino acids 35-47 inhibited these actions of mCRP. Our results thus provide evidence for the generation of mCRP in a human disease and suggest that mCRP actively controls the pathogenesis of lupus nephritis by regulating complement activation. Therefore, amino acids 35-47 constitute a functional autoimmune epitope on CRP that can be targeted therapeutically and diagnostically.
ISSN:1046-6673
1533-3450
DOI:10.1681/ASN.2016070735