Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study.
Smoking, Porphyromonas gingivalis and the immune response to citrullinated autoantigens before the clinical onset of rheumatoid arthritis in a Southern European nested case-control study.
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DOI：
10.1186/s12891-015-0792-y
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发表时间：
2015-11-04
影响因子：
2.3
通讯作者：
Venables PJ
中科院分区：
文献类型：
--
作者：
Fisher BA;Cartwright AJ;Quirke AM;de Pablo P;Romaguera D;Panico S;Mattiello A;Gavrila D;Navarro C;Sacerdote C;Vineis P;Tumino R;Lappin DF;Apatzidou D;Culshaw S;Potempa J;Michaud DS;Riboli E;Venables PJ
瓜氨酸化蛋白（ACPA）抗体在RA诊断前几年出现。牙龈卟啉单胞菌表达自己的肽精氨酸脱亚胺酶（PPAD），是ACPA反应的一个被提出的病因因素。吸烟是acpa阳性类风湿性关节炎和牙周炎的危险因素。我们的目的是在一个前瞻性队列中研究这些因素与RA风险的关系。我们进行了一项巢式病例对照研究，从欧洲癌症和营养前瞻性调查的四个人群中确定ra前病例，并与三个对照组相匹配。吸烟和其他协变量的数据从基线问卷中获得。检测α-烯醇化酶、纤维蛋白原、波形蛋白和PPAD对CCP2和瓜氨酸肽的抗体。针对精氨酸牙龈痛（RgpB）的抗体被用作牙龈卟啉菌感染的标记物，并在健康对照者和牙周炎患者的单独队列中得到验证。我们研究了103例ra前期病例。RA的发展与几种ACPA特异性相关，但与瓜氨酸化PPAD肽的抗体无关。吸烟者的RgpB和PPAD肽抗体水平较高，但与RA或RA前自身免疫的风险无关。曾经吸烟但不现在吸烟与α-烯醇化酶抗体（OR 4.06; 95% CI 1.02, 16.2对0.54;0.09-3.73）和纤维蛋白原肽抗体（OR 4.24; 95% CI 1.2-14.96对0.58;0.13-2.70）以及RA的后期发展（OR 2.48; 95% CI 1.27-4.84对1.57;0.85-2.93）相关，与吸烟强度无关。在临床发病之前，吸烟仍然是类风湿性关节炎的一个危险因素。在这个队列中，牙龈卟啉卟啉与RA前自身免疫或RA发病前早期的风险无关。PPAD肽抗体不是ACPA个体发生的早期特征。
Antibodies to citrullinated proteins (ACPA) occur years before RA diagnosis. Porphyromonas gingivalis expresses its own peptidylarginine deiminase (PPAD), and is a proposed aetiological factor for the ACPA response. Smoking is a risk factor for both ACPA-positive RA and periodontitis. We aimed to study the relation of these factors to the risk of RA in a prospective cohort. We performed a nested case–control study by identifying pre-RA cases in four populations from the European Prospective Investigation into Cancer and nutrition, matched with three controls. Data on smoking and other covariates were obtained from baseline questionnaires. Antibodies to CCP2 and citrullinated peptides from α-enolase, fibrinogen, vimentin and PPAD were measured. Antibodies to arginine gingipain (RgpB) were used as a marker for P.gingivalis infection and validated in a separate cohort of healthy controls and subjects with periodontitis. We studied 103 pre-RA cases. RA development was associated with several ACPA specificities, but not with antibodies to citrullinated PPAD peptides. Antibody levels to RgpB and PPAD peptides were higher in smokers but were not associated with risk of RA or with pre-RA autoimmunity. Former but not current smoking was associated with antibodies to α-enolase (OR 4.06; 95 % CI 1.02, 16.2 versus 0.54; 0.09-3.73) and fibrinogen peptides (OR 4.24; 95 % CI 1.2-14.96 versus 0.58; 0.13-2.70), and later development of RA (OR 2.48; 95 % CI 1.27-4.84 versus 1.57; 0.85-2.93), independent of smoking intensity. Smoking remains a risk factor for RA well before the clinical onset of disease. In this cohort, P.gingivalis is not associated with pre-RA autoimmunity or risk of RA in an early phase before disease-onset. Antibodies to PPAD peptides are not an early feature of ACPA ontogeny.