Baeten Dominique, Demetter Pieter, Cuvelier Claude A, Kruithof Elli, Van Damme Nancy, De Vos Martine, Veys Eric M, De Keyser Filip
Department of Rheumatology, OK121B, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium.
J Pathol. 2002 Mar;196(3):343-50. doi: 10.1002/path.1044.
The objective of this study was to investigate CD163+ macrophages in the synovial membrane of patients with spondyloarthropathy (SpA). Immunohistochemistry was performed on synovium of 17 SpA and 18 rheumatoid arthritis (RA) patients, on colonic biopsies of 16 SpA patients and ten healthy controls, and on paired synovial biopsies of eight SpA patients, before and after anti-TNFalpha therapy. Phenotype and cytokine production were analysed by flow cytometry. CD163+ macrophages were increased in the synovial lining and sublining in SpA versus RA, as well as in colonic lamina propria in SpA versus controls. The number of CD163+ macrophages in the synovial sublining correlated with C-reactive protein levels and erythrocyte sedimentation rate. Paralleling the increase of CD163, HLA-DR was increased in the synovial lining and sublining of SpA. In contrast, the co-stimulatory molecules CD80 and CD86 and the dendritic cell markers CD1a and CD83 were scarce in SpA synovium. Flow cytometry indicated that CD163+ macrophages expressed high levels of HLA-DR and could produce in vitro tumour necrosis factor alpha (TNFalpha) but not interleukin-10 (IL-10). Finally, anti-TNFalpha therapy in vivo induced a decrease of CD163+ macrophages in the synovial lining and sublining. In conclusion, macrophages expressing the scavenger receptor CD163 are increased in synovium and in colonic mucosa in SpA, highlighting the relationship between joint and gut in this disease. The correlation with inflammatory parameters, the expression of HLA-DR, the production of TNFalpha but not IL-10, and the reduction by anti-TNFalpha therapy support a role for CD163+ macrophages in the synovial inflammation in SpA.
本研究的目的是调查脊柱关节炎(SpA)患者滑膜中CD163+巨噬细胞的情况。对17例SpA患者和18例类风湿关节炎(RA)患者的滑膜、16例SpA患者和10例健康对照者的结肠活检组织以及8例SpA患者抗TNFα治疗前后的配对滑膜活检组织进行免疫组织化学检测。通过流式细胞术分析表型和细胞因子产生情况。与RA相比,SpA患者滑膜衬里和衬里下层以及与对照相比,SpA患者结肠固有层中的CD163+巨噬细胞增多。滑膜衬里下层中CD163+巨噬细胞的数量与C反应蛋白水平和红细胞沉降率相关。与CD163的增加并行,SpA滑膜衬里和衬里下层中HLA-DR增加。相反,共刺激分子CD80和CD86以及树突状细胞标志物CD1a和CD83在SpA滑膜中很少见。流式细胞术表明,CD163+巨噬细胞表达高水平的HLA-DR,并且在体外可产生肿瘤坏死因子α(TNFα),但不产生白细胞介素-10(IL-10)。最后,体内抗TNFα治疗导致滑膜衬里和衬里下层中CD163+巨噬细胞减少。总之,在SpA患者的滑膜和结肠黏膜中,表达清道夫受体CD163的巨噬细胞增多,突出了该疾病中关节与肠道之间的关系。与炎症参数的相关性、HLA-DR的表达、TNFα而非IL-10的产生以及抗TNFα治疗的减少支持CD163+巨噬细胞在SpA滑膜炎症中起作用。