Klareskog Lars, Padyukov Leonid, Rönnelid Johan, Alfredsson Lars
Rheumatology Unit, Department of Medicine, Karolinska Institutet/Karolinska University Hospital, Stockholm, Sweden.
Curr Opin Immunol. 2006 Dec;18(6):650-5. doi: 10.1016/j.coi.2006.06.004. Epub 2006 Sep 28.
The combined role of genes, environment and immunity in the development of rheumatoid arthritis (RA) has been the subject of recent investigations. New data support a gene-environment interaction between smoking and the MHC class II HLA-DRB1 shared epitope (SE) genes in anti-citrulline antibody (anti-CP(+)) RA but not in anti-CP(-) disease. These data from genetic epidemiology, together with information on citrullination in the lungs of smokers, have prompted the formulation of a new etiological hypothesis for anti-CP(+) RA, suggesting that smoking in the context of HLA-DR SE might trigger immunity to citrulline-modified proteins and that this immunity, after several years, might cause arthritis.
基因、环境和免疫在类风湿性关节炎（RA）发病过程中的综合作用一直是近期研究的主题。新数据支持吸烟与抗瓜氨酸抗体（抗CP(+)）RA中的MHC II类HLA - DRB1共享表位（SE）基因之间存在基因 - 环境相互作用，但在抗CP(-)疾病中不存在这种相互作用。这些来自遗传流行病学的数据，连同吸烟者肺部瓜氨酸化的信息，促使人们为抗CP(+) RA提出了一种新的病因假说，表明在HLA - DR SE背景下吸烟可能引发对瓜氨酸修饰蛋白的免疫反应，并且这种免疫反应在数年后可能导致关节炎。
