Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo, 116-8567, Japan,
Rheumatol Int. 2014 Jan;34(1):125-30. doi: 10.1007/s00296-012-2626-7. Epub 2013 Jan 19.
The aim of this study was to investigate immunohistological changes in mitogen-activated protein kinases (MAPKs) in the synovium following treatment with golimumab, compared with methotrexate (MTX). We assessed synovial tissues for 13 different molecules to detect cytokine levels histologically from 10 methotrexate (MTX)-treated rheumatoid arthritis (RA) patients as controls and 10 golimumab plus MTX-treated RA patients. Synovium samples from both groups were assessed by hematoxylin and eosin (HE) staining and analyzed for expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), CD4 (T cells), CD8 (T cells), CD20 (B cells), CD68 (macrophages), receptor activator of nuclear (kappa) B ligand (RANKL), bromodeoxyuridine (BrdU), CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (ERK1/ERK2), and phospho-c-Jun N-terminal kinase (JNK), by an immunohistological examination. HE staining showed that there was a significant decrease in cell proliferation in the synovium in RA patients who received golimumab compared with the controls. TNF-α, IL-6, MMP3, BrdU, p38, and ERK were not seen at significant levels in either group. On the other hand, CD4, CD8, CD20, CD29, CD68, RANKL, and JNK were significantly decreased in the golimumab group compared with the control. Based on a histological analysis of the synovium, it appears that the efficacy of the treatment with golimumab may involve the inhibition of cell proliferation, with decreases in T cells, B cells, macrophages, β-1 integrin, RANKL, and JNK in the synovium, compared with MTX treatment, in RA.
本研究旨在探讨与甲氨蝶呤（MTX）相比，戈利木单抗治疗后滑膜中丝裂原活化蛋白激酶（MAPKs）的免疫组织化学变化。我们评估了 10 例接受 MTX 治疗的类风湿关节炎（RA）患者（对照组）和 10 例接受戈利木单抗联合 MTX 治疗的 RA 患者的滑膜组织中的 13 种不同分子，以从组织学上检测细胞因子水平。对两组滑膜样本进行苏木精和伊红（HE）染色，并分析肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、基质金属蛋白酶-3（MMP-3）、CD4（T 细胞）、CD8（T 细胞）、CD20（B 细胞）、CD68（巨噬细胞）、核因子（kappa）B 配体（RANKL）、溴脱氧尿苷（BrdU）、CD29（β-1 整联蛋白）、磷酸化 p38 MAPK（Tyr180/Tyr182）、磷酸化 p44/42 MAPK（ERK1/ERK2）和磷酸化 c-Jun N-末端激酶（JNK）的表达。HE 染色显示，与对照组相比，接受戈利木单抗治疗的 RA 患者滑膜中细胞增殖显著减少。两组均未检测到 TNF-α、IL-6、MMP3、BrdU、p38 和 ERK 达到显著水平。另一方面，与对照组相比，戈利木单抗组的 CD4、CD8、CD20、CD29、CD68、RANKL 和 JNK 明显减少。根据滑膜的组织学分析，与 MTX 治疗相比，戈利木单抗治疗可能通过抑制细胞增殖、减少 T 细胞、B 细胞、巨噬细胞、β-1 整联蛋白、RANKL 和 JNK 来发挥疗效。
