Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity - Biologic and clinical implications in autoimmune arthritis
Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity - Biologic and clinical implications in autoimmune arthritis
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DOI：
10.1002/art.21190
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发表时间：
2005-07-01
影响因子：
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通讯作者：
De Keyser, F
中科院分区：
文献类型：
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作者：
De Rycke, L;Baeten, D;De Keyser, F
Objective.分析单克隆抗体英夫利西单抗或可溶性受体依那西普长期阻断肿瘤坏死因子α（TNF α）过程中自身抗体诱导的临床和生物学相关性。34例脊柱关节病（SpA）和59例类风湿关节炎（RA）患者接受英夫利西单抗治疗2年。此外，20例SpA患者接受依那西普治疗1年。盲法分析血清中的抗核抗体（ANA）、抗双链DNA（抗dsDNA）抗体、抗可提取核抗原（抗ENA）抗体以及抗组蛋白、抗核小体和抗心磷脂抗体（aCL）。抗dsDNA抗体为同型抗体。大量接受英夫利昔单抗治疗的SpA或RA患者在第1年后出现新诱导的ANA（分别为61.8%和40.7%）和抗dsDNA抗体（分别为70.6%和49.2%），但在第1年和第2年之间未观察到进一步增加。相反，在依那西普治疗的SpA患者中仅偶尔观察到ANA和抗dsDNA抗体的诱导（各10%的患者）。同种分型显示几乎完全是IgM或IgM/伊加抗dsDNA抗体，其在治疗中断后消失。英夫利西单抗和依那西普均未诱导其他狼疮相关反应，如抗ENA抗体、抗组蛋白抗体或抗核小体抗体，且未观察到临床相关狼疮样症状。类似地，英夫利昔单抗而非依那西普选择性增加IgM而非IgG aCL滴度。突出的ANA和抗dsDNA自身抗体反应并不是TNF α阻滞剂的纯粹类效应，很大程度上仅限于短期IgM反应，并且与狼疮的其他血清学或临床体征无关。ACL的类似结果表明，体液免疫调节可能是英夫利西单抗治疗的一个更普遍的特征。
Objective. To analyze the clinical and biologic correlates of autoantibody induction during longer-term tumor necrosis factor alpha (TNF alpha) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept.Methods. Thirty-four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti-double-stranded DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA) antibodies, and antihistone, antinucleosome, and anticardiolipin antibodies (aCL). The anti-dsDNA antibodies were isotyped.Results. High numbers of infliximab-treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti-dsDNA antibodies (70.6% and 49.2%, respectively) after I year, but no further increase between year I and year 2 was observed. In contrast, induction of ANAs and anti-dsDNA antibodies was observed only occasionally in the etanercept-treated patients with SpA (10% of patients each). Iso-typing revealed almost exclusively IgM or IgM/IgA anti-dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus-related reactivities such as anti-ENA antibodies, antihistone antibodies, or antinucleosome antibodies, and no clinically relevant lupus-like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers.Conclusion. The prominent ANA and anti-dsDNA autoantibody response is not a pure class effect of TNF alpha blockers, is largely restricted to short-term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment.