Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab
Serum levels of anti-CCP antibodies, anti-MCV antibodies and RF IgA in the follow-up of patients with rheumatoid arthritis treated with rituximab
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DOI：
10.1007/s13317-010-0013-5
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发表时间：
2010-11-01
影响因子：
--
通讯作者：
Tonutti, Elio
中科院分区：
文献类型：
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作者：
Fabris, Martina;De Vita, Salvatore;Tonutti, Elio
类风湿性关节炎 (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 具有更高的特异性，因此比 RF 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，其信息量比 RF 少。最近，据报道，抗瓜氨酸波形蛋白 (a-MCV) 抗体测试可以识别 APCA 的特定亚组，该亚组可能对抗环瓜氨酸肽 (aCCP) 抗体呈阴性。关于 RF，RF IgA 同种型被描述为比总 RF 更具体的糜烂性关节损伤标志物。我们研究的目的是在接受 B 淋巴细胞耗竭型利妥昔单抗 (RTX) 治疗的 RA 患者的随访中监测 a-CCP、a-MCV、总 RF 和 RF IgA 水平，以检测这些自身抗体模式的任何差异或特殊性，特别是与它们作为治疗反应预测标志物的潜在用途有关。我们研究了 30 名接受 RTX 治疗的 RA 患者。所有患者之前均对至少 6 个月的缓解疾病抗风湿药物（DMARD；甲氨蝶呤、来氟米特、环孢素、氯喹）治疗和/或至少 6 个月的抗 TNF 生物制剂治疗无反应。使用 EULAR 标准 (DAS28) 在第 + 6 个月对 RTX 反应进行评估。在基线（第一次输注 RTX 之前）以及 1、3 和 6 个月后测定 a-CCP、a-MCV、总 RF 和 RF IgA。在治疗前获得的血清样本中，还测定了 B 淋巴细胞增殖必需的两种细胞因子：白细胞介素 6 (IL-6) 和 B 淋巴细胞刺激剂 (BLyS)。在随访期间发现所有患者的所有测试抗体均显着且一致地减少，对 RTX 的反应程度没有差异。值得注意的是，在基线时，通常在患者中观察到所有自身抗体滴度较高，然后对 RTX 表现出更好的反应。最后，患者血清中 IL-6 和 BLyS 浓度与所研究的自身抗体是否存在有关，没有差异，细胞因子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，a-MCV 与 aCCP 的比较，以及 RF IgA 与常规总 RF 的比较，都没有为接受 RTX 治疗的 RA 患者的随访提供任何额外的预测信息。
Rheumatoid arthritis (RA) is characterized by the presence of circulating rheumatoid factor (RF) and anti citrullinated 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 (aCCP) 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 aCCP, nor RF IgA compared to routine total RF, provided any additional predictive information in the follow-up of patients with RA treated with RTX.