Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis.
Autoantibodies Against Unmodified and Citrullinated Human Endogenous Retrovirus K Envelope Protein in Patients With Rheumatoid Arthritis.
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DOI：
10.3899/jrheum.201492
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发表时间：
2022-01
期刊：
影响因子：
--
通讯作者：
Mustelin T
中科院分区：
文献类型：
--
作者：
Wang X;Hefton A;Ni K;Ukadike KC;Bowen MA;Eckert M;Stevens A;Lood C;Mustelin T
类风湿性关节炎（RA）患者中已报告了针对人内源性逆转录病毒K（HERV-K）编码蛋白的自身抗体，但其相关性（如果有的话）仍未得到解决。我们重新审视了这个问题，并测试了这种自身抗体是否可以与HERV-K包膜（Env）蛋白上的瓜氨酸化表位反应。用未修饰的Env蛋白和用蛋白质精氨酸脱亚胺酶4（PAD 4）瓜氨酸化的Env进行免疫印迹和ELISA。包括100例RA患者的血清、32例幼年特发性关节炎（JIA）患者的血浆以及健康成人和儿童对照。评价抗体反应性与患者临床和实验室变量的相关性。我们复制并扩展了已发表的数据，表明RA或JIA患者具有抗HERV-K Env的自身抗体，其中一些具有高滴度。抗HERV-K抗体与吸烟和循环髓过氧化物酶-DNA复合物相关，提示中性粒细胞非凋亡性死亡。此外，大多数RA患者（而非JIA患者）的自身抗体与由PAD 4瓜氨酸化的Env反应更强烈。这些抗瓜氨酸Env自身抗体与血清阳性相关，并且在糜烂性疾病患者中倾向于更高。我们的数据表明，抗HERV-K免疫在RA和JIA中升高，并且可能与RA中的致病蛋白瓜氨酸有关。
Autoantibodies against proteins encoded by human endogenous retrovirus K (HERV-K) have been reported in patients with rheumatoid arthritis (RA), but their relevance, if any, has remained unresolved. We revisited this question and tested if such autoantibodies may react with citrullinated epitopes on the envelope (Env) protein of HERV-K. Immunoblotting and ELISAs were conducted with unmodified Env protein and with Env citrullinated by protein arginine deiminase 4 (PAD4). Sera from 100 patients with RA, plasma from 32 patients with juvenile idiopathic arthritis (JIA), and healthy adult and pediatric controls were included. Antibody reactivity was evaluated for correlations with clinical and laboratory variables of the patients. We replicated and expanded upon published data suggesting that patients with RA or JIA have autoantibodies against HERV-K Env, some with high titers. Anti-HERV-K antibodies correlated with cigarette smoking and with circulating myeloperoxidase-DNA complexes indicative of nonapoptotic neutrophil cell death. Further, most of the patients with RA, but not those with JIA, had autoantibodies that reacted more strongly with Env that was citrullinated by PAD4. These anticitrullinated Env autoantibodies correlated with seropositivity and tended to be higher in patients with erosive disease. Our data suggest that anti-HERV-K immunity is elevated in RA and JIA and may have a connection with pathogenic protein citrullination in RA.
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