Department of Clinical Immunology and Rheumatology, Hiroshima University Hospital, Hiroshima City, Hiroshima, Japan.
PLoS One. 2013 Aug 1;8(8):e69944. doi: 10.1371/journal.pone.0069944. Print 2013.
Factor XIII is one of the twelve coagulation factors and also known as a fibrin-stabilizing factor. In 2012, we encountered a male RA patient with hemorrhagic factor XIII deficiency who had been treated with tocilizumab for two years. There are few reports regarding the relationship between tocilizumab (a humanized monoclonal antibody against the interleukin-6 receptor (IL-6R)) and factor XIII. We measured the factor XIII activity levels in the plasma of 40 RA patients (10 patients treated without biologics, 30 patients treated with biologics (15 patients treated with necrosis factor inhibitors and 15 patients treated with tocilizumab)) and 19 healthy controls. Consequently, the tocilizumab group exhibited lower levels than the other three groups according to the Steel-Dwass test (P<0.01). Furthermore, we compared the plasma factor XIII activity levels and the plasma factor XIII concentrations in the RA patients treated with biologics. Pearson's correlation test was used to assess the relationship between the factor XIII activity levels and the plasma factor XIII concentrations (r=0.449, P=0.019). According to the multiple regression analysis, the treatment with tocilizumab is an independent risk factor for plasma factor XIII reduction in RA patients. In conclusion, RA patients treated with tocilizumab, an IL-6R blocker, are at risk of developing acquired factor XIII deficiency. The mechanisms underlying the reduced factor XIII activity observed in RA patients treated with tocilizumab may result from the quantitative reduction in the plasma. These data imply that IL-6 plays an important role in maintaining the factor XIII activity level.
凝血 XIII 因子是 12 种凝血因子之一，也被称为纤维蛋白稳定因子。2012 年，我们遇到了一名患有出血性凝血 XIII 因子缺乏症的男性 RA 患者，他已经接受托珠单抗治疗两年了。关于托珠单抗（一种针对白细胞介素-6 受体（IL-6R）的人源化单克隆抗体）和凝血 XIII 因子之间的关系，已有少数报道。我们测量了 40 名 RA 患者（10 名未接受生物制剂治疗的患者，30 名接受生物制剂治疗的患者（15 名接受肿瘤坏死因子抑制剂治疗的患者和 15 名接受托珠单抗治疗的患者）和 19 名健康对照者的血浆凝血 XIII 因子活性水平。根据 Steel-Dwass 检验，托珠单抗组的水平明显低于其他三组（P<0.01）。此外，我们比较了接受生物制剂治疗的 RA 患者的血浆凝血 XIII 因子活性水平和血浆凝血 XIII 因子浓度。采用 Pearson 相关检验评估凝血 XIII 因子活性水平与血浆凝血 XIII 因子浓度之间的关系（r=0.449，P=0.019）。根据多元回归分析，托珠单抗治疗是 RA 患者血浆凝血 XIII 因子减少的独立危险因素。总之，接受 IL-6R 阻滞剂托珠单抗治疗的 RA 患者有发生获得性凝血 XIII 因子缺乏的风险。托珠单抗治疗的 RA 患者凝血 XIII 因子活性降低的机制可能与血浆中凝血 XIII 因子的数量减少有关。这些数据表明，IL-6 在维持凝血 XIII 因子活性水平方面发挥着重要作用。
