Department of Rheumatology, Renji Hospital, Shanghai Jiaotong University School of Medicine, 145 Shan Dong Middle Road, Shanghai 200001, PR China.
Arthritis Res Ther. 2011 Jan 31;13(1):R9. doi: 10.1186/ar3230.
Inadequate 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.
Purified 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.
Anti-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).
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.
巨噬细胞对凋亡细胞的清除不充分是自身耐受破坏的原因之一。在巨噬细胞上表达的 A 类清道夫受体、巨噬细胞胶原样受体（MARCO）和清道夫受体 A（SR-A）在摄取凋亡细胞方面发挥重要作用。先前的研究报道了狼疮易感小鼠和系统性红斑狼疮（SLE）患者存在抗 MARCO 抗体。本研究旨在探讨各种自身免疫性疾病，特别是 SLE 患者中抗 A 类清道夫受体抗体的流行情况，以及这些自身抗体在巨噬细胞吞噬清除凋亡细胞中的功能意义。
使用纯化的重组清道夫受体富含半胱氨酸（SRCR）多肽（MARCO 的配体结合域）和重组 SR-A 作为抗原，通过酶联免疫吸附试验检测未经治疗的 SLE（n = 65）、类风湿关节炎（n = 65）、原发性干燥综合征（n = 25）和健康献血者（n = 85）血清中的抗-SRCR 和抗-SR-A 抗体。通过流式细胞术测定从 SLE 患者或健康对照者中纯化的 IgG 对巨噬细胞吞噬凋亡细胞的影响。
抗-SRCR 抗体存在于 SLE 患者（18.5%）和类风湿关节炎患者（3.1%）中，但不存在于原发性干燥综合征患者中。抗-SR-A 抗体存在于 SLE 患者（33.8%）、类风湿关节炎患者（13.8%）和原发性干燥综合征患者（12.0%）中。抗-SRCR 或抗-SR-A 抗体阳性的 SLE 患者 IgG 与健康对照 IgG 相比，对凋亡细胞与巨噬细胞结合的抑制率更高（均 P < 0.05）。抗-SRCR 和抗-SR-A 抗体均阳性的 SLE 患者 IgG 与健康对照 IgG 相比，对巨噬细胞摄取凋亡细胞的抑制率显著更高（P < 0.05）。
我们的结果表明，针对 A 类清道夫受体的自身抗体可能通过损害凋亡碎片的清除而导致自身耐受破坏，并在自身免疫性疾病的发病机制中发挥作用，特别是在 SLE 中。
