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Serum levels of anti-CCP antibodies anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab

机译:利妥昔单抗治疗的类风湿关节炎患者的抗CCP抗体抗MCV抗体和RF IgA水平

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摘要

Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anticitrullinated peptide antibodies (ACPA), which are positive in about 70–80% of patients. APCA have a higher specificity and therefore a higher diagnostic power than RF, but are less informative than RF in monitoring the course of the disease in patients under treatment. Recently, it has been reported that the anticitrullinated vimentin (a-MCV) antibody test can identify a particular subgroup of APCA that may be negative for anticyclic citrullinated peptide (a-CCP) antibodies. Concerning RF, the RF IgA isotype has been described as a more specific marker of erosive joint damage than total RF. The aim of our study was to monitor the levels of a-CCP, a-MCV, total RF and RF IgA in the follow-up of patients with RA treated with B-lymphocytedepletive rituximab (RTX), to detect any differences or peculiarities in patterns of these autoantibodies, especially in relation to their potential use as predictive markers of therapeutic response. We studied 30 patients with RA treated with RTX. All patients were previously unresponsive to at least 6 months of therapy with disease-modifying antirheumatic drugs (DMARDs; methotrexate, leflunomide, cyclosporine, chloroquine) and/or at least 6 months of therapy with anti-TNF biologics. The evaluation of response to RTX was made at month +6 using the EULAR criteria (DAS28). a-CCP, a-MCV, total RF and RF IgA were determined at baseline (before the first infusion of RTX) and after 1, 3 and 6 months. In serum samples obtained before treatment two cytokines essential for Blymphocyte proliferation, interleukin 6 (IL-6) and B-lymphocyte stimulator (BLyS) were also determined. In all patients a significant and consistent reduction in all the tested antibodies was found during follow-up, with no differences in respect of the degree of response to RTX. Of note, at baseline, generally a higher titre of all autoantibodies was seen in patients who then showed a better response to RTX. Finally, there were no differences in serum concentrations of IL-6 and BLyS in patients in relation to the presence or absence of the autoantibodies investigated, nor was there any significant correlation between the serum concentrations of the cytokines and the titres of the autoantibodies. Thus, neither a-MCV compared to a- CCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.
机译:类风湿关节炎(RA)的特征是存在循环类风湿因子(RF)和抗瓜氨酸肽抗体(ACPA),约70-80%的患者呈阳性。 APCA比RF具有更高的特异性,因此具有更高的诊断能力,但在监测接受治疗的患者的病程方面,其信息却不如RF。最近,有报道说抗瓜氨酸波形蛋白(a-MCV)抗体检测可以鉴定出可能是抗环瓜氨酸肽(a-CCP)抗体阴性的APCA特定亚组。关于RF,RF IgA同种型已被描述为比总RF更具体的侵蚀性关节损伤标记。我们研究的目的是监测在接受B淋巴细胞耗竭利妥昔单抗(RTX)治疗的RA患者的随访中a-CCP,a-MCV,总RF和RF IgA的水平,以检测其任何差异或特殊性。这些自身抗体的模式,特别是与它们作为治疗反应的预测标志物的潜在用途有关。我们研究了30例接受RTX治疗的RA患者。所有患者先前对使用疾病改良抗风湿药(DMARD;甲氨蝶呤,来氟米特,环孢素,氯喹)至少6个月的治疗无效,和/或至少6个月使用抗TNF生物制剂的治疗无效。使用EULAR标准(DAS28)在+6个月对RTX的响应进行评估。在基线(首次输注RTX之前)以及1、3和6个月后确定a-CCP,a-MCV,总RF和RF IgA。在治疗前获得的血清样品中,还确定了两种对于淋巴细胞增殖必不可少的细胞因子,即白介素6(IL-6)和B淋巴细胞刺激物(BLyS)。在随访期间,所有患者的所有测试抗体均显着且持续降低,对RTX的反应程度无差异。值得注意的是,在基线时,通常对那些对RTX表现出更好反应的患者所有抗体的滴度更高。最后,与所研究的自身抗体的存在与否有关,患者的血清IL-6和BLyS浓度没有差异,细胞因子的血清浓度与自身抗体滴度之间也没有任何显着相关性。因此,无论是与a-CCP相比,a-MCV还是与常规总RF相比,RF IgA都不能在接受RTX治疗的RA患者的随访中提供任何其他预测信息。

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