支气管扩张症是类风湿关节炎慢性细菌感染诱导自身免疫的模型。
Bronchiectasis is a Model for Chronic Bacterial Infection Inducing Autoimmunity in Rheumatoid Arthritis.
机构信息
Kennedy Institute, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
Queen Elizabeth Hospital, Gateshead, UK, and University of Exeter Medical School, Exeter, UK.
出版信息
Arthritis Rheumatol. 2015 Sep;67(9):2335-42. doi: 10.1002/art.39226.
OBJECTIVE
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).
METHODS
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.
RESULTS
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.
CONCLUSION
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.
目的
通过研究单纯支气管扩张症（BR）患者和 BR 合并类风湿关节炎（BR/RA）患者，探讨慢性严重细菌感染产生类风湿因子（RF）和抗瓜氨酸化蛋白抗体（ACPAs）的潜力。
方法
我们研究了 122 例单纯 BR 患者、50 例 BR/RA 患者、50 例无肺部疾病的 RA 患者、87 例哮喘患者和 79 名健康对照者。采用自动分析仪检测 RF 水平，采用环瓜氨酸肽 2（CCP-2）检测 ACPAs。采用酶联免疫吸附试验测定α-烯醇化酶肽 1（CEP-1）、Cit-vimentin 和 Cit-fibrinogen 对其精氨酸含有的对照肽（精氨酸含有的α-烯醇化酶肽 1[REP-1]、vimentin 和 fibrinogen）的精细特异性。
结果
BR 患者和对照组中，分别有 39%和 42%为既往吸烟者。与对照组相比，BR 患者血清 RF 阳性率升高（25%比 10%），CCP-2 抗体、CEP-1 抗体、Cit-vimentin 抗体和 Cit-fibrinogen 抗体的频率也升高（5%比 0%、7%比 4%、7%比 4%和 12%比 4%），但仅 RF 和 Cit-fibrinogen 的差异有统计学意义（P < 0.05）。与对照组相比，BR 患者抗精氨酸对照肽抗体的频率也相应升高（REP-1 为 19%比 4%[P < 0.01]；vimentin 为 16%比 4%[P < 0.05]），表明 BR 患者的 ACPA 反应不是瓜氨酸特异性的。吸收研究进一步证实了这种缺乏瓜氨酸特异性。在 BR/RA 患者中，所有 ACPA 反应均具有高度瓜氨酸特异性。
结论
支气管扩张症是肺部细菌感染导致 RA 发生自身免疫的一种罕见但有效的模型。我们的研究表明，在自身免疫耐受崩溃的早期阶段，ACPA 反应不是瓜氨酸特异性的，但在发生 BR/RA 的 BR 患者中，反应变得更加特异。
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