Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes.
Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes.
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DOI：
10.1186/s13075-018-1520-4
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发表时间：
2018-02-26
影响因子：
4.9
通讯作者：
van der Woude D
中科院分区：
文献类型：
--
作者：
de Moel EC;Derksen VFAM;Stoeken G;Trouw LA;Bang H;Goekoop RJ;Speyer I;Huizinga TWJ;Allaart CF;Toes REM;van der Woude D
血清阳性类风湿性关节炎（RA）的自身抗体谱是非常多样的，包括各种同种型和抗体的多个翻译后修饰。目前尚不清楚这种自身抗体谱的不同宽度是否与治疗结果相关。因此，我们研究了作为潜在免疫病理学标志物的RA自身抗体谱的组成是否影响初始和长期治疗结果。在IMPROVED研究的399例血清阳性RA患者的血清中，在基线和药物逐渐减量时抽取，我们测量了抗环瓜氨酸肽-2和抗氨甲酰化蛋白抗体的IgG、IgM和伊加同种型，IgM和伊加类风湿因子，以及对四种瓜氨酸肽和两种乙酰化肽（抗修饰蛋白抗体（AMPA））的反应性。我们研究了自身抗体谱的宽度对（1）0至4个月之间疾病活动评分（DAS）44的变化，（2）随访1至2年之间实现的初始无药物缓解（DFR，无药物DAS 44 < 1.6），以及（3）长期持续DFR直至末次随访的影响。基线时具有广泛自身抗体谱的患者具有显著更好的早期治疗应答：ΔDAS 0-4个月1-2、3-4和5-6 vs 7-8种同种型，-1.5（p < 0.001）、-1.7（p = 0.03）和-1.8（p = 0.04）vs-2.2。对于AMPA数也观察到类似的结果。然而，具有广泛基线自身抗体谱的患者获得的初始DFR较少。对于长期持续的DFR，不再与自身抗体反应的广度相关。当在逐渐减量时评估自身抗体时，观察到类似的趋势。广泛的基线自身抗体谱与更好的早期治疗应答相关。基线自身抗体谱的宽度，反映了对几种不同自身抗原的耐受性的破坏和广泛的同种型转换，可能表明更活跃的体液自身免疫，这可能使潜在的疾病过程最初更容易被药物抑制。与长期持续DFR缺乏相关性表明基线自身抗体谱的相关性随时间推移而降低。ISRCTN11916566。2006年11月7日登记。EudraCT，2006- 06186-16。2007年7月16日登记。本文的在线版本（10.1186/s13075-018-1520-4）包含补充材料，可供授权用户使用。
The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti‐carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS)44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 < 1.6) achieved between 1 and 2 years of follow up, and (3) long-term sustained DFR until last follow up. Patients with a broad autoantibody profile at baseline had a significantly better early treatment response: ΔDAS 0–4 months of 1–2, 3–4, and 5–6 vs 7–8 isotypes, -1.5 (p < 0.001), -1.7 (p = 0.03), and -1.8 (p = 0.04) vs -2.2. Similar results were observed for AMPA number. However, patients with a broad baseline autoantibody profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed. A broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time. ISRCTN11916566. Registered on 7 November 2006. EudraCT, 2006- 06186-16. Registered on 16 July 2007. The online version of this article (10.1186/s13075-018-1520-4) contains supplementary material, which is available to authorized users.
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影响因子：
4.9
作者：
Brink M;Verheul MK;Rönnelid J;Berglin E;Holmdahl R;Toes RE;Klareskog L;Trouw LA;Rantapää-Dahlqvist S
通讯作者：
Rantapää-Dahlqvist S
影响因子：
--
作者：
Fabris, Martina;De Vita, Salvatore;Tonutti, Elio
通讯作者：
Tonutti, Elio
影响因子：
3.9
作者：
Shu, Jenny;Bykerk, Vivian P.;Pope, Janet E.
通讯作者：
Pope, Janet E.
影响因子：
27.4
作者：
Figueiredo, Camille P.;Bang, Holger;Schett, Georg
通讯作者：
Schett, Georg
影响因子：
3.9
作者：
Barra, Lillian;Pope, Janet E.;Bykerk, Vivian P.
通讯作者：
Bykerk, Vivian P.