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类风湿因子和抗瓜氨酸化蛋白抗体作为预测类风湿关节炎对英夫利昔单抗反应的价值:一项探索性研究。

The value of rheumatoid factor and anti-citrullinated protein antibodies as predictors of response to infliximab in rheumatoid arthritis: an exploratory study.

机构信息

Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands.

出版信息

Rheumatology (Oxford). 2011 Aug;50(8):1487-93. doi: 10.1093/rheumatology/ker010. Epub 2011 Mar 30.

Abstract

OBJECTIVE

It remains unclear whether autoantibodies are useful biomarkers to tailor the choice of biological treatment in RA. We investigated the relationship between the presence and levels of different RF and ACPA isotypes and the response to TNF blockade in an exploratory study.

METHODS

A total of 101 active RA patients were prospectively treated with infliximab (3 mg/kg). Changes in disease activity were monitored by the 28-joint DAS (DAS-28). Serum levels of different isotypes [immunoglobulins M, G and A (IgM, IgG and IgA)] of RF and anti-citrullinated peptide antibodies were measured by ELISA.

RESULTS

The mean DAS-28 decreased from 5.9 (1.1) at baseline to 4.0 (1.3) at Week 16 of infliximab treatment (P < 0.001). High baseline levels of different isotypes of RF (all P < 0.008), ACPA IgM (P = 0.008) and ACPA IgG (P = 0.07) were associated with an absolute decrease in DAS-28 after TNF blockade. This relationship persisted after adjusting for DAS-28 at baseline. However, the different isotypes of baseline RF and ACPA levels accounted for only a small proportion of variance in treatment response (RF: R² between 7 and 12% and ACPA: R² between 4 and 7%). The simultaneous presence of all three isotypes of RF or ACPA had no additive value.

CONCLUSION

Presence as well as the titres of RF and IgM ACPA at baseline are significantly correlated with better response to infliximab treatment. However, this correlation is not strong enough to allow a reliable prediction in individual patients. Trial Registration. ISRCTN Register, http://www.controlled-trials.com/isrctn/, ISRCTN36847425.

摘要

目的

自身抗体是否可作为选择生物制剂治疗类风湿关节炎(RA)的有用生物标志物仍不清楚。我们在一项探索性研究中调查了不同 RF 和 ACPA 同种型的存在和水平与 TNF 阻断治疗反应之间的关系。

方法

共前瞻性纳入 101 例活动性 RA 患者,接受英夫利昔单抗(3mg/kg)治疗。通过 28 关节疾病活动度评分(DAS28)监测疾病活动度的变化。采用 ELISA 法检测不同同种型[免疫球蛋白 M、G 和 A(IgM、IgG 和 IgA)]的 RF 和抗瓜氨酸肽抗体的血清水平。

结果

英夫利昔单抗治疗 16 周时,平均 DAS28 从基线时的 5.9(1.1)降至 4.0(1.3)(P<0.001)。基线时不同同种型 RF(均 P<0.008)、ACPA IgM(P=0.008)和 ACPA IgG(P=0.07)的高基线水平与 TNF 阻断后 DAS28 的绝对降低相关。在调整基线 DAS28 后,这种相关性仍然存在。然而,基线 RF 和 ACPA 水平的不同同种型仅能解释治疗反应的一小部分变异(RF:R²在 7%至 12%之间,ACPA:R²在 4%至 7%之间)。同时存在三种 RF 或 ACPA 同种型并无附加价值。

结论

基线时 RF 和 IgM ACPA 的存在及其滴度与对英夫利昔单抗治疗的更好反应显著相关。然而,这种相关性还不够强,无法在个体患者中进行可靠预测。

试验注册

ISRCTN 注册,http://www.controlled-trials.com/isrctn/,ISRCTN36847425。

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