抗PAD2和抗PAD4自身抗体在类风湿关节炎中的临床应用价值探讨

Clinical relevance of autoantibodies targeting peptidylarginine deiminases 2 and 4 in rheumatoid arthritis

目的评估类风湿关节炎(RA)患者中抗PAD2自身抗体(α-PAD2)和抗PAD4自身抗体(α-PAD4)联合检测的临床应用价值。方法本研究收集了2018年11月至2019年11月北京大学人民医院住院的RA患者148例和非RA的关节炎对照(DC组)35例。同时收集了2019年6—7月北京大学人民医院体检的健康体检者44名。通过ELISA方法检测血清中α-PAD2和α-PAD4水平。根据需要,采用Mann-Whitney U检验、Kruskal-Wallis(KW)检验、χ^(²)检验或Fisher精确检验进行统计学分析。相关性分析采用逻辑回归模型。结果α-PAD2和α-PAD4在RA组、DC组及HC组中的阳性率分别为26.4%(39/148)和20.9%(31/148)、5.7%(2/35)和5.7%(2/35)、4.5%(2/44)和2.3%(1/44)。α-PAD4阳性的RA患者较α-PAD4阴性患者病程更长(17.3±13.2年比8.6±10.2年,P<0.001),其肺间质性疾病(ILD)发生率更高(54.8%比25.6%,P=0.002)。α-PAD2与RA-ILD间未发现显著相关(OR:0.797,P=0.579),而α-PAD4与RA-ILD间存在显著相关(OR:3.521,P=0.002)。对于血清阳性的RA患者,α-PAD4抗体仅与RA-ILD呈现弱相关(OR:2.324,P=0.046),而联合检测α-PAD2和α-PAD4,即α-PAD2阴性同时α-PAD4阳性可以显著提高其与RA-ILD的相关性(OR:4.059,P=0.007)。结论α-PAD2存在于RA中,其对于RA的诊断具有一定的潜在价值。此外,α-PAD2联合α-PAD4检测可以增强α-PAD4对于RA-ILD风险的预测价值。因此,α-PAD2作为RA新的潜在生物标志物,可能作为现有RA血清学标志物的重要补充。

Objective To evaluate the clinical performance of anti-peptidylarginine deiminase 2(PAD2)and anti-PAD4 antibodies combined testing in a Chinese rheumatoid arthritis(RA)cohort.Methods A total of 148 RA inpatients and 35 patients with non-RA arthritis as controls(DC)were recruited from November,2018 to November,2019 in Peking University People′s Hospital.In addition,a total of 44 healthy controls(HC)who went to Peking University People′s Hospital for annual physical examination were collected from June 2019 to July 2019.Theα-PAD2 andα-PAD4 level in clinical specimens were determined by ELISA.Statistical analysis was performed by the Mann-Whitney U test,the Kruskal-Wallis(KW)test,the χ^(2) test or the Fisher′s Exact Test,as necessary.Correlation analysis were performed by logistic regression.Resultsα-PAD2 andα-PAD4 were present in 26.4%(39/148)and 20.9%(31/148)patients with RA,5.7%(2/35)and 5.7%DC(2/35)and 4.5%(2/44)and 2.3%HC(2/44),respectively.α-PAD4-positive RA patients displayed significantly longer disease duration compared toα-PAD4-negative RA patients(17.3±13.2 years vs 8.6±10.2 years,P<0.001).α-PAD4-positive RA patients showed a significantly higher incidence of interstitial lung disease(ILD)compared to those withoutα-PAD4(54.8%vs 25.6%,P=0.002).No associations betweenα-PAD2 and ILD were found(OR:0.797,P=0.579).In contrast,significant associations betweenα-PAD4 and ILD were found(OR:3.521,P=0.002).In seropositive RA,α-PAD4 displayed a weak correlation with ILD(OR:2.324,P=0.046),but this association was greatly enhanced when combined withα-PAD2[anti-PAD2(-)](OR:4.059,P=0.007).Conclusions The findings delineate the clinical relevance ofα-PAD2 andα-PAD4 in RA and suggest that the combined testing forα-PAD2 andα-PAD4 may provide additional diagnostic value to the current clinically available assays in RA,in particular in identifying patients at risk of RA-ILD.