The University of Queensland Diamantina Institute, University of Queensland, Princess Alexandra Hospital, Brisbane, 4102, QLD, Australia.
Mater Research Institute-UQ, Faculty of Medicine, University of Queensland, Brisbane, 4102, QLD, Australia.
Best Pract Res Clin Rheumatol. 2019 Dec;33(6):101497. doi: 10.1016/j.berh.2020.101497. Epub 2020 Mar 19.
Rheumatoid Arthritis (RA) is a severe, chronic autoimmune disease that affects 1% of the world's population. Familial risk contributes 50% of the risk of seropositive RA, with strongest risks seen in first-degree relatives. Smoking increases the risk of developing anti-citrullinated peptide antibody (ACPA) RA, particularly in individuals with high-risk RA-susceptibility alleles. Other contributory environmental risks including particulate exposure, periodontal disease, bronchiectasis, diet, obesity and the oral contraceptive impact respiratory, oral, intestinal and genital tract mucosal sites. Furthermore, the first signs of autoimmunity may appear at mucosal sites e.g. sputum ACPA-IgA and IgG. While oral and faecal dysbiosis are well described, there is no consistent single bacterial species that appears to drive RA. Animal and human data suggest a model in which multiple environmental influences impact mucosal immune function through the host genetics through enhanced mucosal permeability and the traffic of pro-inflammatory PAMPs and the amplification of autoimmune responses. In some cases, autoimmunity may be driven by cross-reactivity, or mimicry, to pathogen-specific antigens, particularly where the host immune system fails to support their rapid control and elimination.
类风湿关节炎（RA）是一种严重的慢性自身免疫性疾病，影响全球 1%的人口。家族风险占血清阳性 RA 风险的 50%，一级亲属的风险最高。吸烟会增加抗瓜氨酸化肽抗体（ACPA）RA 的发病风险，尤其是在具有高风险 RA 易感性等位基因的个体中。其他环境风险因素包括颗粒暴露、牙周病、支气管扩张、饮食、肥胖和口服避孕药会影响呼吸道、口腔、肠道和生殖道黏膜部位。此外，自身免疫的最初迹象可能出现在黏膜部位，例如痰 ACPA-IgA 和 IgG。虽然口腔和粪便菌群失调已得到充分描述，但似乎没有一种单一的细菌物种能够驱动 RA。动物和人类数据表明，在这种模型中，多种环境影响通过宿主遗传学通过增强黏膜通透性和促炎 PAMP 的流动以及自身免疫反应的放大来影响黏膜免疫功能。在某些情况下，自身免疫可能是由针对病原体特异性抗原的交叉反应或模拟驱动的，尤其是在宿主免疫系统未能支持其快速控制和消除的情况下。
