Anti-C1q autoantibodies from systemic lupus erythematosus patients enhance CD40-CD154-mediated inflammation in peripheral blood mononuclear cells .

Objectives: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease with complex pathogenic mechanisms. Complement C1q has been shown to play a major role in SLE, and autoantibodies against C1q (anti-C1q) are strongly associated with SLE disease activity and severe lupus nephritis suggesting a pathogenic role for anti-C1q. Whereas C1q alone has anti-inflammatory effects on human monocytes and macrophages, C1q/anti-C1q complexes favor a pro-inflammatory phenotype.

Autoantibodies against complement component C1q in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is the archetype of a systemic autoimmune disease, but the multifaceted pathogenic mechanisms leading to inflammation and organ damage are not fully understood. Homozygous deficiency of complement C1q, the first component of the classical pathway of complement, is strongly associated with the development of SLE, thus pointing at a primarily protective role of C1q. However, while most SLE patients do not have hereditary C1q deficiency, there is indirect evidence for the importance of C1q in the inflammatory processes of the disease, including hypocomplementemia as a result of activation via the classical pathway, deposition of C1q in affected tissues and the occurrence of autoantibodies against C1q (anti-C1q).