Bronchiectasis is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis.
Bronchiectasis is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis.
复制标题
DOI：
10.1002/art.39226
复制
发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Venables PJ
中科院分区：
文献类型：
--
作者：
Quirke AM;Perry E;Cartwright A;Kelly C;De Soyza A;Eggleton P;Hutchinson D;Venables PJ
通过研究单纯支气管扩张（BR）患者和BR伴类风湿关节炎（BR/RA）患者，检查慢性重度细菌感染产生类风湿因子（RF）和抗瓜氨酸化蛋白抗体（ACPA）的可能性。我们研究了122例单纯BR患者、50例BR/RA患者和50例无肺部疾病的RA患者，以及87例哮喘患者和79例健康受试者作为对照。使用自动分析仪测量RF水平，并使用环瓜氨酸肽2（CCP-2）检测ACPA。通过酶联免疫吸附试验测定瓜氨酸化α-烯醇化酶肽1（CEP-1）、Cit-波形蛋白和Cit-纤维蛋白原相对于其含精氨酸对照肽（含精氨酸α-烯醇化酶肽1 [REP-1]、波形蛋白和纤维蛋白原）的精细特异性。在BR患者和对照受试者中，分别有39%和42%的人曾吸烟。与对照组相比，BR患者血清中RF阳性的频率增加（25% vs 10%），CCP-2（5% vs 0%）、CEP-1（7% vs 4%）、Cit-波形蛋白（7% vs 4%）和Cit-纤维蛋白原（12% vs 4%）抗体的频率也增加，尽管只有RF和Cit-纤维蛋白原的差异具有显著性（P < 0.05）。与对照组相比，我们观察到BR患者中含精氨酸对照肽的抗体频率相应增加（REP-1，19% vs 4% [P < 0.01];波形蛋白，16% vs 4% [P < 0.05]），表明BR患者中的ACPA反应不是瓜氨酸特异性的。吸收研究进一步证实了瓜氨酸缺乏特异性。在BR/RA患者中，所有ACPA应答均具有高度瓜氨酸特异性。支气管扩张是一种不常见但有效的模型，用于通过肺部细菌感染诱导RA的自身免疫。我们的研究表明，在耐受性破坏的早期阶段，ACPA反应不是瓜氨酸特异性的，但在发生BR/RA的BR患者中变得更具特异性。
To examine the potential of chronic severe bacterial infection to generate rheumatoid factor (RF) and anti–citrullinated protein antibodies (ACPAs), by studying patients with bronchiectasis (BR) alone and BR patients with rheumatoid arthritis (BR/RA). We studied 122 patients with BR alone, 50 patients with BR/RA, and 50 RA patients without lung disease, as well as 87 patients with asthma and 79 healthy subjects as controls. RF levels were measured using an automated analyzer, and cyclic citrullinated peptide 2 (CCP‐2) was used to detect ACPAs. The fine specificities of citrullinated α‐enolase peptide 1 (CEP‐1), Cit‐vimentin, and Cit‐fibrinogen to their arginine‐containing control peptides (arginine‐containing α‐enolase peptide 1 [REP‐1], vimentin, and fibrinogen) were measured by enzyme‐linked immunosorbent assay. Among the BR patients and control subjects, 39% and 42%, respectively, were ever‐smokers. The frequency of RF positivity in serum was increased in BR patients compared with controls (25% versus 10%), as were the frequencies of antibodies to CCP‐2 (5% versus 0%), CEP‐1 (7% versus 4%), Cit‐vimentin (7% versus 4%), and Cit‐fibrinogen (12% versus 4%), although only the differences for RF and Cit‐fibrinogen were significant (P < 0.05). We observed a corresponding increase in the frequency of antibodies to the arginine‐containing control peptides in BR patients compared with controls (for REP‐1, 19% versus 4% [P < 0.01]; for vimentin, 16% versus 4% [P < 0.05]), demonstrating that the ACPA response in patients with BR is not citrulline specific. The lack of citrulline specificity was further confirmed by absorption studies. In BR/RA patients, all ACPA responses were highly citrulline specific. Bronchiectasis is an unusual but potent model for the induction of autoimmunity in RA by bacterial infection in the lung. Our study suggests that the ACPA response is not citrulline specific during the early stages of tolerance breakdown but becomes more specific in patients with BR in whom BR/RA develops.