Anti-Citrullinated Protein Antibodies in Patients with Rheumatoid Arthritis: Biological Effects and Mechanisms of Immunopathogenesis

被引:83
作者
Wu, Chao-Yi [1 ,2 ]
Yang, Huang-Yu [2 ,3 ]
Lai, Jenn-Haung [4 ,5 ]
机构
[1] Chang Gung Mem Hosp, Dept Pediat, Div Allergy Asthma & Rheumatol, Taoyuan 333, Taiwan
[2] Chang Gung Univ, Coll Med, Taoyuan 333, Taiwan
[3] Chang Gung Mem Hosp, Dept Nephrol, Taoyuan 333, Taiwan
[4] Chang Gung Univ, Chang Gung Mem Hosp, Dept Internal Med, Div Allergy Immunol & Rheumatol, Taoyuan 333, Taiwan
[5] Natl Def Med Ctr, Grad Inst Med Sci, Taipei 114, Taiwan
关键词
anti-citrullinated protein antibodies; rheumatoid arthritis; pathogenesis; FC-GAMMA RECEPTORS; B-CELL DEPLETION; SYNOVIAL-FLUID; IMMUNE-COMPLEXES; PEPTIDYLARGININE DEIMINASE; PEPTIDE ANTIBODIES; PORPHYROMONAS-GINGIVALIS; INFLAMMATORY RESPONSE; ARGININE DEIMINASES; AUTOANTIBODIES;
D O I
10.3390/ijms21114015
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Individuals with high anti-citrullinated protein antibody (ACPA) titers have an increased risk of developing rheumatoid arthritis (RA). Although our knowledge of the generation and production of ACPAs has continuously advanced during the past decade, our understanding on the pathogenic mechanisms of how ACPAs interact with immune cells to trigger articular inflammation is relatively limited. Citrullination disorders drive the generation and maintenance of ACPAs, with profound clinical significance in patients with RA. The loss of tolerance to citrullinated proteins, however, is essential for ACPAs to exert their pathogenicity. N-linked glycosylation, cross-reactivity and the structural interactions of ACPAs with their citrullinated antigens further direct their biological functions. Although questions remain in the pathogenicity of ACPAs acting as agonists for a receptor-mediated response, immune complex (IC) formation, complement system activation, crystallizable fragment gamma receptor (Fc gamma R) activation, cross-reactivity to joint cartilage and neutrophil extracellular trap (NET)-related mechanisms have all been suggested recently. This paper presents a critical review of the characteristics and possible biological effects and mechanisms of the immunopathogenesis of ACPAs in patients with RA.
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页数:23
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