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.
Highlights
Accumulation in blood and tissues of post-apoptotic remnants is discussed to be of etiological and pathological importance for patients with Systemic lupus erythematosus (SLE) since the pathognomonic autoantigens are sequestered inside viable cells
Black histograms correspond to BSA– FITC binding as control for annexin A5 (AxA5), C-reactive protein (CRP), acetylated low density lipoprotein (acLDL), NPn lectin; to anti-C3c and anti-C1q staining in the presence of decomplemented serum; and to anti-IgG in the presence of NHD serum, respectively
secondary necrotic cells (SNEC) show a random distribution of autoantibody targets on their surfaces that do not overlap with the nuclear chromatin (Figure 1C)
Summary
Accumulation in blood and tissues of post-apoptotic remnants is discussed to be of etiological and pathological importance for patients with Systemic lupus erythematosus (SLE) since the pathognomonic autoantigens are sequestered inside viable cells. They are, not accessible to the immune system in healthy persons. Sensibilization of cellular remnants with autoantibodies shifts the phagocytosis of dead cells from liver and spleen to blood–borne phagocytes, which do not take up unsensitized material This antibody-dependent pro-inflammatory pathway initiates an amplification loop of inflammation and contributes to the chronification of the autoimmune response (Munoz et al, 2010c)
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