CRP/anti-CRP Antibodies Assembly on the Surfaces of Cell Remnants Switches Their Phagocytic Clearance Toward Inflammation

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the production of autoantibodies, formation of immune complexes (IC), and activation of complement that ultimately fuel acute and/or chronic inflammation. Accumulation in blood and tissues of post-apoptotic remnants is considered of etiological and pathological importance for patients with SLE. Besides receptors directly recognizing apoptotic cells, soluble opsonins of the innate immune system bind apoptotic material dependent on the stage of apoptosis. We describe the binding to the surface of secondary necrotic cells (SNEC) of the serum opsonin CRP and further opsonins. We show that anti-dsDNA and anti-CRP autoantibodies bind and sensitize SNEC. Autoantibody-sensitized SNEC were cleared by macrophages in vitro and induced a pro-inflammatory cytokine response. In conclusion, anti-CRP, CRP, and SNEC form a ternary pyrogen endowed with strong pro-inflammatory capabilities which is able to maintain and perpetuate chronic inflammation.

Anti-C1q Autoantibodies from Systemic Lupus Erythematosus Patients Induce a Proinflammatory Phenotype in Macrophages

“…However, our experiments were performed using patient-derived high-affinity Abs to correlate with disease activity (65), as well as patient-derived macrophages. In addition, our data on antiC1q are in line with other studies demonstrating that autoantibodies from SLE patients can modify the response of phagocytes (8,66,67).…”

High prevalence of autoantibodies to C-reactive protein in patients with chronic hepatitis C infection: association with liver fibrosis and portal inflammation

“…This could indicate that anti-CRP antibodies in HCV patients may partially be targeted against native epitopes of CRP and not to hidden neo-epitopes (monomeric) CRP as is the case in lupus. Potential pathogenic roles for anti-CRP include impaired clearance of immune complexes and apoptotic debris as well as loss of complement-inhibitory effects of CRP in solution [14,[39][40][41][42]; both scenarios could result in advanced damage in targeted organs [16,37,[43][44][45].…”

C-reactive protein, immunoglobulin G and complement co-localize in renal immune deposits of proliferative lupus nephritis

“…It has further been shown in vitro that CRP and anti-CRP antibodies assemble on the surfaces of cell remnants and induce a pro-inflammatory response when exposed to macrophages [53].…”