Department of Orthopaedic Surgery, Tokyo Women's Medical University, Medical Center East, 2-1-10 Nishiogu, Arakawa, Tokyo 116-8567, Japan.
Rheumatol Int. 2012 Sep;32(9):2669-74. doi: 10.1007/s00296-011-2021-9. Epub 2011 Jul 26.
The aim of this study was to investigate histological changes of bone marrow in response to tocilizumab for rheumatoid arthritis (RA). After tocilizumab therapy, bone marrow tissues were extracted from ten RA patients at the time of total knee arthroplasty (TKA). Control samples were obtained from ten RA patients who underwent MTX mono-therapy. Histological examination of structural differences between the tocilizumab and control groups in bone marrow was performed using hematoxylin and eosin (H&E) to evaluate differences. In immunohistochemical examination, the expression of seven molecules including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), CD68, osteoprotegerin (OPG), receptor activator of nuclear kappa B ligand (RANKL), CD4 and osteopontin (OPN) were compared between two groups. NTx was significantly low at 44.5 ± 2 nM BCE/mM Cr compared with control at 73.2 ± 8 nM BCE/mM Cr. Immunohistochemical examination revealed that the bone marrow tissues of the RA patients who underwent tocilizumab therapy demonstrated significant positive OPG as compared with the control. However, immunohistochemical examinations after tocilizumab revealed that TNF-α, IL-6, CD68, CD4, OPN and RANKL were not significantly different with control of MTX in bone marrow. Therefore, treatment with tocilizumab increased the expression of OPG as the histological changes with respect to inhibit RANKL-related bone resorption of bone marrow in RA.
本研究旨在探讨托珠单抗治疗类风湿关节炎（RA）时骨髓的组织学变化。在进行全膝关节置换术（TKA）时，从 10 名接受托珠单抗治疗的 RA 患者中提取骨髓组织。对照组则来自于 10 名接受 MTX 单药治疗的 RA 患者。通过苏木精和伊红（H&E）染色评估两组骨髓的结构差异，对托珠单抗组和对照组的骨髓进行组织学检查。在免疫组织化学检查中，比较了两组中包括肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、CD68、护骨素（OPG）、核因子κB 受体激活剂配体（RANKL）、CD4 和骨桥蛋白（OPN）在内的 7 种分子的表达。与对照组 73.2±8 nM BCE/mM Cr 相比，托珠单抗组的 NTx 显著降低（44.5±2 nM BCE/mM Cr）。免疫组织化学检查显示，与对照组相比，接受托珠单抗治疗的 RA 患者的骨髓组织中 OPG 表达显著增加。然而，托珠单抗治疗后的免疫组织化学检查显示，TNF-α、IL-6、CD68、CD4、OPN 和 RANKL 在骨髓中的表达与 MTX 对照组无明显差异。因此，托珠单抗治疗增加了 OPG 的表达，这是 RA 骨髓中与抑制 RANKL 相关的骨吸收的组织学变化。
