Anti-class a scavenger receptor autoantibodies from systemic lupus erythematosus patients impair phagocytic clearance of apoptotic cells by macrophages in vitro.

Abstract

INTRODUCTION:

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.

METHODS:

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.

RESULTS:

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).

CONCLUSIONS:

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.

• Authors: Xiao-wei Chen, Yan Shen, Chuan-yin Sun, Feng-xia Wu, Yi Chen, Cheng-de Yang
• Journal: Arthritis research & therapy (Arthritis Res Ther) Vol. 13 Issue 1 Pg. R9 (Jan 31 2011) ISSN: 1478-6362 [Electronic] England
• PMID: 21281474 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Autoantibodies
• Autoantigens
• MARCO protein, human
• Receptors, Immunologic
• Scavenger Receptors, Class A

Topics

• Adult
• Apoptosis (immunology)
• Autoantibodies (blood, immunology)
• Autoantigens (immunology)
• Cell Separation
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Humans
• In Vitro Techniques
• Lupus Erythematosus, Systemic (blood, immunology)
• Macrophages (immunology)
• Male
• Middle Aged
• Phagocytosis (immunology)
• Receptors, Immunologic (immunology)
• Scavenger Receptors, Class A (immunology)