Department of Immunology, Genetics and Pathology, University of Uppsala, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
Clin Exp Rheumatol. 2021 Jul-Aug;39(4):879-882. doi: 10.55563/clinexprheumatol/4bcmdb. Epub 2021 Mar 30.
To examine the association between individual rheumatoid arthritis (RA) autoantibodies, sex and age at RA onset.
Anti-CCP2, IgA-, IgG- and IgM-RF were analysed centrally in baseline sera from 1600 RA patients diagnosed within one year of RA symptom onset. Cut-offs for RF isotypes were determined at the 98th percentile based on RA-free controls, close to the 98.4% anti-CCP2 specificity.
Anti-CCP2 was found in 1020 patients (64%), IgA RF in 692 (43%), IgG RF in 529 (33%) and IgM RF in 916 (57%) of the patients. When assessed one by one, anti-CCP2 and IgM RF were both associated with lower age at RA diagnosis. When assessed in one joint model, the association to IgM RF weakened and a strong association between IgA RF and higher age at RA diagnosis appeared. IgA RF and IgG RF associated with male sex, and IgM RF with female sex, with no difference for anti-CCP2. When the model was adjusted for sex, the association between IgM RF and age disappeared, whereas the strong associations between IgA RF and high age and between anti-CCP2 and low age at diagnosis remained. Further adjustments for smoking, shared epitope and inclusion year did not change the outcome. Univariate analyses stratified on anti-CCP2 and IgA RF status confirmed the findings.
Anti-CCP associate with low, and IgA RF with high age at RA onset. RFs and anti-CCP2 display opposing association with sex. These results underscore that studies on RA phenotypes in relation to autoantibodies should accommodate age and sex.
研究个体类风湿关节炎 (RA) 自身抗体、性别和发病年龄之间的关联。
在发病一年内确诊的 1600 例 RA 患者的基线血清中，对抗 CCP2、IgA、IgG 和 IgM-RF 进行了中心分析。根据无 RA 的对照者，基于第 98 百分位数确定了 RF 同种型的截断值，接近 98.4%的抗 CCP2 特异性。
在 1020 例患者（64%）中发现了抗 CCP2，在 692 例（43%）患者中发现了 IgA RF，在 529 例（33%）患者中发现了 IgG RF，在 916 例（57%）患者中发现了 IgM RF。逐个评估时，抗 CCP2 和 IgM RF 均与 RA 诊断年龄较低相关。在一个联合模型中评估时，与 IgM RF 的关联减弱，而与 RA 诊断年龄较高相关的 IgA RF 之间的关联较强。IgA RF 和 IgG RF 与男性性别相关，IgM RF 与女性性别相关，而抗 CCP2 则无差异。当模型调整为性别时，IgM RF 与年龄的关联消失，而 IgA RF 与高年龄、抗 CCP2 与低年龄诊断之间的强关联仍然存在。进一步调整吸烟、共享表位和纳入年份并未改变结果。根据抗 CCP2 和 IgA RF 状态进行的单变量分析证实了这些发现。
抗 CCP2 与 RA 发病年龄较低相关，而 IgA RF 与 RA 发病年龄较高相关。RFs 和抗 CCP2 与性别呈相反关联。这些结果强调了在与自身抗体相关的 RA 表型研究中，应考虑年龄和性别因素。
