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所有血清阳性类风湿关节炎患者对 B 细胞耗竭治疗的良好 EULAR 反应的生物标志物:发病机制的线索。

Biomarkers of good EULAR response to the B cell depletion therapy in all seropositive rheumatoid arthritis patients: clues for the pathogenesis.

机构信息

Division of Rheumatology, Catholic University of the Sacred Heart, Rome, Italy.

出版信息

PLoS One. 2012;7(7):e40362. doi: 10.1371/journal.pone.0040362. Epub 2012 Jul 30.

Abstract

OBJECTIVE

To find out whether a high number of auto-antibodies can increase the probability of a "good-EULAR response" and to identify the possible biomarkers of response in seropositive rheumatoid arthritis (RA) patients undergoing the B cell depletion therapy (BCDT).

PATIENTS AND METHODS

One hundred and thirty-eight patients with long standing RA (LSRA), 75% non or poorly responsive to one or more TNFα blockers, all seropositive for at least one autoantibody (AAB) (RF-IgM, RF-IgA, RF-IgG, anti-MCV, ACPA-IgG, ACPA-IgA, ACPA-IgM) received one full course of BCDT. The major outcomes (moderate or good-EULAR response) were assessed after 6 months of therapy. The IL6 and BAFF levels were also determined.

RESULTS

At a 6-month follow-up, 33 (23.9%) of the RA patients achieved a good EULAR response. Having up to 5-AABs positivity increased the chances for treatment response. After a logistic regression analysis, however, only 4 baseline factors arose as associated with a good-EULAR response: no steroid therapy (OR = 6.25), a lymphocyte count <1875/uL (OR = 10.74), a RF-IgG level >52.1 IU/ml (OR = 8.37) and BAFF levels <1011 pg/ml (OR = 7.38). When all the AABs, except for RF-IgM and ACPA-IgG, were left in the analysis, the two final predictors were no-steroid therapy and low lymphocyte count.

DISCUSSION

The number of AABs increased the chances of being a "good-EULAR" responder. The only predictors, however, at the baseline of a good response in this seropositive cohort of RA patients were 2 simple variables--no steroids and lymphocyte count--and two laboratory assays--IgG-RF and BAFF.

摘要

目的

探讨大量自身抗体是否会增加“良好的 EULAR 反应”的可能性,并确定接受 B 细胞耗竭治疗(BCDT)的血清阳性类风湿关节炎(RA)患者的可能反应生物标志物。

方法

138 例长期 RA(LSRA)患者,75%对一种或多种 TNFα 阻滞剂无反应或反应不佳,均至少有一种自身抗体(AAB)(RF-IgM、RF-IgA、RF-IgG、抗 MCV、ACPA-IgG、ACPA-IgA、ACPA-IgM)阳性,接受了一个完整疗程的 BCDT。主要结局(中度或良好的 EULAR 反应)在治疗 6 个月后评估。还测定了 IL6 和 BAFF 水平。

结果

在 6 个月的随访中,33 例(23.9%)RA 患者达到了良好的 EULAR 反应。具有多达 5 种 AAB 阳性增加了治疗反应的机会。然而,经过逻辑回归分析,只有 4 个基线因素与良好的 EULAR 反应相关:无类固醇治疗(OR=6.25)、淋巴细胞计数<1875/uL(OR=10.74)、RF-IgG 水平>52.1 IU/ml(OR=8.37)和 BAFF 水平<1011 pg/ml(OR=7.38)。当分析中只剩下除 RF-IgM 和 ACPA-IgG 以外的所有 AAB 时,两个最终预测因子是无类固醇治疗和低淋巴细胞计数。

讨论

AAB 的数量增加了成为“良好的 EULAR 反应者”的机会。然而,在这个血清阳性的 RA 患者队列中,只有两个简单的变量(无类固醇治疗和淋巴细胞计数)和两个实验室检测(IgG-RF 和 BAFF)是良好反应的基线预测因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bec3/3408482/4f31e9308875/pone.0040362.g001.jpg

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