RA患者痰液中也存在RF和CCP自身抗体

摘要：在类风湿关节炎的发病过程中，血清中的类风湿因子及抗瓜氨酸抗体水平的升高通常导致了炎性关节炎症状的出现，也说明了引起类风湿关节炎自身免疫紊乱的原因可能始于关节外。虽然产生自身抗体的解剖学位置是未知的，但现有的证据证明IgA的自身抗体的出现是早于类风湿关节炎的症状的出现的，并且起源于粘膜。由于吸烟和职业病是类风湿关节炎的危险因素，而且有报道证实肺的炎性病变与血清中类风关的自身抗体呈阳性相关，因此提示肺可能是产生类风关相关自身抗体的脏器。然而检测肺是否是产生类风关相关自身抗体的脏器的方法仍然存在很多挑战。因此，通过检测痰液中的自身抗体以及通过痰液中的自身抗体与血清中的自身抗体的分析可能可以被用来判定肺是否是产生类风关相关自身抗体的脏器并且判断类风湿关节炎的的进展情况。为了验证上述观点，Van C. Willis等研究者通过对21例的健康对照，49例的高风险人群及14例早期RA患者的类风湿因子及抗瓜氨酸抗体的亚型进行的分析。结果提示39%的有类风关风险的但血清学检测阴性的人群中痰液中存在上述自身抗体阳性，65%的有类风关风险的血清学检测阳性的人群中痰液中存在上述自身抗体阳性，86%的早期类风关病人存在上述自身抗体阳性。在早期的类风关病人中，血清中的自身抗体的水平高于痰液中的自身抗体的水平，而在有类风关风险的血清学检测阳性的人群中，痰液中的自身抗体的水平高于血清中自身抗体的水平。数据证实了肺脏是产生自身抗体的主要脏器，并且在类风关的发病过程中有着重要的地位。

附原文：Abstract OBJECTIVE: To evaluate the generation of rheumatoid arthritis (RA)-related autoantibodies in the lung.METHODS: Simultaneous collection of serum and induced sputum was performed in 21 healthy controls, 49 at-risk subjects without inflammatory arthritis but at risk of RA due to family history or seropositivity for anti-citrullinated protein antibodies, and 14 subjects with early RA. Samples were tested for anti-cyclic citrullinated peptide 2 (anti-CCP2), anti-CCP3, anti-CCP3.1, rheumatoid factor isotypes IgM, IgG, and IgA, and total IgM, IgG, and IgA.RESULTS: One or more autoantibodies were present in sputum of 39% of at-risk seronegative subjects, 65% of at-risk seropositive subjects, and 86% of subjects with early RA. In at-risk seronegative subjects, the rate of anti-CCP3.1 positivity and the median number of autoantibodies were elevated in sputum versus serum. In subjects with early RA, the rate of positivity for several individual autoantibodies and the median number of autoantibodies were higher in serum than in sputum. Results in at-risk seropositive subjects were intermediate between these groups. In at-risk subjects with autoantibody positivity in sputum, the ratios of autoantibody to total Ig were higher in sputum than in serum, suggesting that these autoantibodies are generated or sequestered in the lung.CONCLUSION: RA-related autoantibodies are detectable in sputum in subjects at risk of RA and in subjects with early RA. In a subset of at-risk subjects, the presence of sputum autoantibodies in the absence of seropositivity, and the increased autoantibody-to-total Ig ratios in sputum, suggest that the lung may be a site of autoantibody generation in the early development of RA. These findings suggest an important role of the lung in the pathogenesis of RA.

附原文：Willis VC, Demoruelle MK, Derber LA, Chartier-Logan CJ, Parish MC, Pedraza IF, Weisman MH, Norris JM, Holers VM, Deane KD. Sputum autoantibodies in patients with established rheumatoid arthritis and subjects at risk of future clinically apparent disease. Arthritis Rheum. 2013 Oct;65(10):2545-54. doi: 10.1002/art.38066.