托珠单抗可降低类风湿关节炎患者滑膜中的 T 细胞，但不降低巨噬细胞，同时增加血清白细胞介素-6 和 RANKL 水平。
Tocilizumab decreases T cells but not macrophages in the synovium of patients with rheumatoid arthritis while it increases the levels of serum interleukin-6 and RANKL.
机构信息
Rheumatology Unit, Department of Gastroentorogy, Dematology and Rheumatology, Karolinska University Hospital, Stockholm, Sweden
Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
出版信息
RMD Open. 2021 Jun;7(2). doi: 10.1136/rmdopen-2021-001662.
OBJECTIVES
Our knowledge about the effect of tocilizumab (TCZ) on the synovium in rheumatoid arthritis (RA) is limited. The aim of this study was to investigate the effect of TCZ on citrullination and on inflammation in the synovial tissue and in the peripheral blood.
METHODS
15 patients with RA underwent synovial biopsy before and 8 weeks after TCZ initiation. Clinical evaluation was performed at baseline and at 8 weeks. Using immunohistochemistry, we evaluated the expression of CD68, CD3, CD20, osteoprotegerin (OPG) and receptor activator for nuclear factor-κB ligand (RANKL) before and after treatment with TCZ. We also analysed the expression of protein arginine deiminase (PAD)-2 and PAD-4 enzymes in the synovial tissue and protein citrullination patterns with the help of anticitrullinated protein antibody (ACPA) clones 1325:04C03 and 1325:01B09. Serum levels of interleukin-6 (IL-6), IL-8, RANKL, OPG and C-terminal crosslinked telopeptide type II collagen were measured by ELISA. Paired-wise Wilcoxon signed-rank test was used to compare median values before and after treatment.
RESULTS
Disease activity in patients was reduced from baseline to 8 weeks. Although PAD-2 and PAD-4 expressions remained unchanged after TCZ treatment, the binding of one ACPA clone decreased in the synovial tissue. TCZ did not affect the number of CD68+ macrophages or CD20+ B cells but induced significant decrease in the number of CD3+ T cells. RANKL and OPG expression remained unchanged in the synovial tissue. A significant increase in the levels of IL-6 and RANKL was observed in the serum. This increase was statistically significant in patients who responded to TCZ (achieving Clinical Disease Activity Index low disease activity or remission) but not in non-responders.
CONCLUSIONS
TCZ reduced synovial T-cell counts but not macrophages. A significant increase of serum IL-6 was observed in responders.
目的
我们对托珠单抗（TCZ）对类风湿关节炎（RA）滑膜的影响知之甚少。本研究旨在探讨 TCZ 对滑膜和外周血中瓜氨酸化和炎症的影响。
方法
15 例 RA 患者在 TCZ 起始前和 8 周后进行滑膜活检。在基线和 8 周时进行临床评估。使用免疫组织化学方法，我们评估了 TCZ 治疗前后 CD68、CD3、CD20、骨保护素（OPG）和核因子-κB 配体受体激活剂（RANKL）的表达。我们还分析了滑膜组织中蛋白精氨酸脱亚氨酶（PAD）-2 和 PAD-4 酶的表达，并使用抗瓜氨酸蛋白抗体（ACPA）克隆 1325:04C03 和 1325:01B09 分析蛋白质瓜氨酸化模式。通过 ELISA 测量血清白细胞介素-6（IL-6）、IL-8、RANKL、OPG 和 C 端交联型 II 型胶原 telopeptide。使用配对符号秩和检验比较治疗前后中位数。
结果
患者的疾病活动度从基线降低到 8 周。尽管 TCZ 治疗后 PAD-2 和 PAD-4 的表达保持不变，但滑膜组织中一种 ACPA 克隆的结合减少了。TCZ 对 CD68+巨噬细胞或 CD20+B 细胞的数量没有影响，但显著减少了 CD3+T 细胞的数量。RANKL 和 OPG 在滑膜组织中的表达保持不变。血清中 IL-6 和 RANKL 的水平显著升高。在对 TCZ 有反应（达到临床疾病活动指数低疾病活动或缓解）的患者中观察到这种增加具有统计学意义，但在无反应者中则不然。
结论
TCZ 减少了滑膜 T 细胞的数量，但没有减少巨噬细胞。在有反应者中观察到血清 IL-6 的显著增加。
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