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Timing of Elevations of Autoantibody Isotypes Prior to Diagnosis of Rheumatoid Arthritis.
Arthritis & Rheumatology ( IF 13.3 ) Pub Date : 2019-12-26 , DOI: 10.1002/art.41091
Lindsay B Kelmenson 1 , Brandie D Wagner 1 , Bryan K McNair 1 , Ashley Frazer-Abel 1 , M Kristen Demoruelle 1 , Dylan T Bergstedt 1 , Marie L Feser 1 , Laura K Moss 1 , Mark C Parish 1 , Elizabeth A Mewshaw 2 , Ted R Mikuls 3 , Jess D Edison 2 , V Michael Holers 1 , Kevin D Deane 1
Affiliation  

OBJECTIVE To evaluate patterns of elevations of isotypes of rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs) pre-rheumatoid arthritis (RA) diagnosis and post-RA diagnosis. METHODS Using the Department of Defense Serum Repository we identified 214 RA cases and 210 matched controls. Up to 3 pre-RA diagnosis and 1 post-RA diagnosis serum samples per subject were tested for RF and for IgA, IgG, and IgM ACPAs. The timing and trajectories of elevations of autoantibodies were evaluated. RESULTS Autoantibody levels were elevated in cases versus controls a mean of 17.9 years before RA diagnosis for IgG ACPA, 14.2 years for IgA-RF, 7.2 years for IgM-RF, 6.2 years for IgA ACPA, and 5.0 years for both IgM ACPA and IgG-RF (P < 0.01 for all comparisons). There were similar relationships for positive or negative autoantibody status, with cases first showing positivity for IgG ACPA 1.9 years pre-RA and for IgA-RF 1.7 years pre-RA, followed by the other isotypes. Only IgA ACPA positivity was significantly increased in post-RA diagnosis samples (19% 0-2 years pre-RA versus 39% >2 years post-RA diagnosis; P = 0.04). All autoantibody levels demonstrated an early initial elevation, a period of stability, then an increase immediately before RA diagnosis. A pre-RA endotype of early elevation of autoantibodies was associated with increased use of biologic therapy, and a higher prevalence of sicca symptoms and lung disease post-RA diagnosis. CONCLUSION Differences in patterns of elevations of autoantibody isotypes have implications for understanding the pathophysiology of RA development. These include understanding what factors drive initial autoantibody elevations compared to what factors (including mucosal) drive later increases in autoantibody levels and a transition to clinically apparent RA, and how pre-RA endotypes may influence post-RA diagnosis phenotypes.

中文翻译:

诊断类风湿关节炎之前自身抗体同种型升高的时间。

目的评估类风湿因子(RF)和抗瓜氨酸化蛋白抗体(ACPAs)的同种型在类风湿关节炎(RA)之前的诊断和RA以后的诊断的升高模式。方法使用国防部血清库,我们确定了214例RA病例和210例匹配的对照。每个受试者最多进行3次RA诊断前和1 RA诊断后血清样品的RF以及IgA,IgG和IgM ACPAs检测。评价了自身抗体升高的时间和轨迹。结果在病例中,与对照相比,自身抗体水平升高,RA诊断前为IgG ACPA,平均为17.9年; IgA-RF为14.2年; IgM-RF为7.2年; IgA ACPA为6.2年; IgM ACPA和IgG均为5.0年。 -RF(所有比较均P <0.01)。阳性或阴性自身抗体状态也存在相似的关系,病例首先显示RA前1.9年对IgG ACPA阳性,RA前1.7年对IgA-RF阳性,其次是其他同种型。RA诊断后样品中仅IgA ACPA阳性显着增加(RA诊断前0-2年为19%,RA诊断后2年以上为39%; P = 0.04)。所有自身抗体水平均显示出初期初始升高,稳定期,然后在RA诊断之前立即升高。RA自身抗体早期升高的内在型与生物疗法的使用增加,RA诊断后的干燥症状和肺部疾病的患病率更高相关。结论自身抗体同种型升高模式的差异对于理解RA的病理生理学具有重要意义。
更新日期:2019-12-27
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