Abstract
IntroductionInadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance. Class A scavenger receptors, macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A), which are expressed on macrophages, play important roles in the uptake of apoptotic cells. A previous study reported the presence of the anti-MARCO antibody in lupus-prone mice and systemic lupus erythematosus (SLE) patients. The purpose of this study was to investigate the prevalence of anti-class A scavenger receptor antibodies in patients with various autoimmune diseases, in particular SLE, and the functional implication of those autoantibodies in the phagocytic clearance of apoptotic cells by macrophages.MethodsPurified recombinant scavenger receptor cysteine-rich (SRCR) polypeptide (ligand-binding domain of MARCO) and recombinant SR-A were used as antigens. By using enzyme-linked immunosorbent assay, the anti-SRCR and anti-SR-A antibodies were detected in the sera of untreated patients with SLE (n = 65), rheumatoid arthritis (n = 65), primary Sjögren syndrome (n = 25), and healthy blood donors (n = 85). The effect of IgG purified from SLE patients or healthy controls on the phagocytosis of apoptotic cells by macrophages was measured by the flow cytometry assay.ResultsAnti-SRCR antibodies were present in patients with SLE (18.5%) and rheumatoid arthritis (3.1%), but not in those with primary Sjögren syndrome. Anti-SR-A antibodies were present in patients with SLE (33.8%), rheumatoid arthritis (13.8%), and primary Sjögren syndrome (12.0%). IgG from SLE patients positive for anti-SRCR or anti-SR-A antibodies showed a higher inhibition rate on binding of apoptotic cells to macrophages than IgG from healthy controls (both P < 0.05). IgG from SLE patients positive for both anti-SRCR and anti-SR-A antibodies showed a significantly higher inhibition rate on ingestion of apoptotic by macrophages than IgG from healthy controls (P < 0.05).ConclusionsOur results indicated that autoantibodies to class A scavenger receptors might contribute to the breakdown of self-tolerance by impairing the clearance of apoptotic debris and play a role in the pathogenesis of autoimmune disease, especially in SLE.
Highlights
Inadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance
Anti-scavenger receptor cysteine-rich (SRCR) antibodies were present in patients with systemic lupus erythematosus (SLE) (18.5%) and rheumatoid arthritis (3.1%), but not in those with primary Sjögren syndrome
Our results indicated that autoantibodies to class A scavenger receptors might contribute to the breakdown of self-tolerance by impairing the clearance of apoptotic debris and play a role in the pathogenesis of autoimmune disease, especially in SLE
Summary
Inadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance. The purpose of this study was to investigate the prevalence of anti-class A scavenger receptor antibodies in patients with various autoimmune diseases, in particular SLE, and the functional implication of those autoantibodies in the phagocytic clearance of apoptotic cells by macrophages. Several lines of evidence suggest that increased apoptosis and impaired phagocytic It is unclear whether macrophages of patients with SLE have intrinsic defects resulting in reduced clearance of apoptotic cells; serum factors have been implicated in the reduced clearance of apoptotic cells by macrophages. Recent studies indicated that class A scavenger receptor member macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A) could bind to apoptotic cells and contribute to the clearance of apoptotic cells [7,8]. It is proposed that autoantibodies blocking scavenger receptors may alter the phagocytosis of apoptotic cells by macrophages, and, thereby, facilitate the development of an autoimmune response
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