Klein-Wieringa Inge R, de Lange-Brokaar Badelog J E, Yusuf Erlangga, Andersen Stefan N, Kwekkeboom Joanneke C, Kroon Herman M, van Osch Gerjo J V M, Zuurmond Anne-Marie, Stojanovic-Susulic Vedrana, Nelissen Rob G H H, Toes René E M, Kloppenburg Margreet, Ioan-Facsinay Andreea
From the Department of Rheumatology, Leiden University Medical Centre; Department of Radiology, Department of Orthopedics, and Department of Clinical Epidemiology, Leiden University Medical Center; TNO, Leiden; Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands; The Janssen Pharmaceutical Companies of Johnson & Johnson, Spring House, Pennsylvania, USA.I.R. Klein-Wieringa*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; B.J. de Lange-Brokaar*, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; E. Yusuf, MD, PhD, Department of Rheumatology, Leiden University Medical Centre; S.N. Andersen, Ing, Department of Rheumatology, Leiden University Medical Centre; J.C. Kwekkeboom, Ing, Department of Rheumatology, Leiden University Medical Centre; H.M. Kroon, PhD, Department of Radiology, Leiden University Medical Center; G.J. van Osch, PhD, Professor, Department of Orthopedics and Otorhinolaryngology, Erasmus MC, University Medical Center; A.M. Zuurmond, PhD, TNO; V. Stojanovic-Susulic, PhD, Janssen Pharmaceutical Companies of Johnson & Johnson; R.G. Nelissen, MD, PhD, Professor, Department of Orthopedics, Leiden University Medical Center; R.E. Toes, PhD, Professor, Department of Rheumatology, Leiden University Medical Centre; M. Kloppenburg, MD, PhD, Professor, Department of Rheumatology, and Department of Clinical Epidemiology, Leiden University Medical Centre; A. Ioan-Facsinay, PhD, Assistant Professor, Department of Rheumatology, Leiden University Medical Centre.
J Rheumatol. 2016 Apr;43(4):771-8. doi: 10.3899/jrheum.151068. Epub 2016 Mar 15.
To get a better understanding of inflammatory pathways active in the osteoarthritic (OA) joint, we characterized and compared inflammatory cells in the synovium and the infrapatellar fat pad (IFP) of patients with knee OA.
Infiltrating immune cells were characterized by flow cytometry in 76 patients with knee OA (mean age 63.3, 52% women, median body mass index 28.9) from whom synovial tissue (n = 40) and IFP (n = 68) samples were obtained. Pain was assessed by the visual analog scale (VAS; 0-100 mm). Spearman rank correlations and linear regression analyses adjusted for sex and age were performed.
Macrophages and T cells, followed by mast cells, were the most predominant immune cells in the synovium and IFP, and were equally abundant in these tissues. Macrophages and T cells secreted mostly proinflammatory cytokines even without additional stimulation, indicating their activated state. Accordingly, most CD4+ T cells had a memory phenotype and contained a significant population of cells expressing activation markers (CD25+, CD69+). Interestingly, the percent of CD69+ T cells was higher in synovial than IFP CD4+ T cells. Preliminary analyses indicated that the number of synovial CD4+ T cells were associated with VAS pain (β 0.51, 95% CI 0.09-1.02, p = 0.02).
Our data suggest that the immune cell composition of the synovium and the IFP is similar, and includes activated cells that could contribute to inflammation through secretion of proinflammatory cytokines. Moreover, preliminary analyses indicate that synovial CD4+ T cells might associate with pain in patients with endstage OA of the knee.
为了更好地了解骨关节炎（OA）关节中活跃的炎症途径，我们对膝骨关节炎患者滑膜和髌下脂肪垫（IFP）中的炎症细胞进行了表征和比较。
采用流式细胞术对76例膝骨关节炎患者（平均年龄63.3岁，52%为女性，体重指数中位数28.9）的浸润免疫细胞进行表征，这些患者的滑膜组织（n = 40）和IFP（n = 68）样本已获取。通过视觉模拟量表（VAS；0 - 100 mm）评估疼痛程度。进行了经性别和年龄调整的Spearman等级相关性分析和线性回归分析。
巨噬细胞和T细胞，其次是肥大细胞，是滑膜和IFP中最主要的免疫细胞，且在这些组织中的数量相当。即使没有额外刺激，巨噬细胞和T细胞也大多分泌促炎细胞因子，表明它们处于激活状态。相应地，大多数CD4 + T细胞具有记忆表型，并且包含大量表达激活标志物（CD25 +、CD69 +）的细胞。有趣的是，滑膜CD4 + T细胞中CD69 + T细胞的百分比高于IFP中的CD4 + T细胞。初步分析表明，滑膜CD4 + T细胞数量与VAS疼痛相关（β = 0.51，95% CI 0.09 - 1.02，p = 0.02）。
我们的数据表明，滑膜和IFP的免疫细胞组成相似，并且包括可通过分泌促炎细胞因子促进炎症的激活细胞。此外，初步分析表明，滑膜CD4 + T细胞可能与膝终末期OA患者的疼痛有关。
