Jansen Diahann T S L, Hameetman Marjolijn, van Bergen Jeroen, Huizinga Tom W J, van der Heijde Désirée, Toes René E M, van Gaalen Floris A
Department of Rheumatology and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
Rheumatology (Oxford). 2015 Apr;54(4):728-35. doi: 10.1093/rheumatology/keu382. Epub 2014 Oct 6.
Increased numbers of IL-17-producing CD4(+) T cells have been observed in AS. However, it is not known whether these CD4(+) T cells are already present in early disease or if this is a late disease phenomenon only. Therefore we aimed to investigate whether IL-17-producing CD4(+) T cells are involved in early active axial SpA, including patients without imaging abnormalities, by determining the frequency and phenotype of IL-17-producing CD4(+) T cells in these patients.
Flow cytometry was used to analyse cytokine production and surface marker expression of peripheral blood mononuclear cells from 31 patients suffering from early active HLA-B27-positive axial SpA fulfilling the Assessment of SpondyloArthritis International Society criteria with or without MRI abnormalities and 21 healthy controls.
Patients with early active axial SpA showed an increased percentage of IL-17-producing CD4(+) T cells compared with healthy controls (mean 1.1% vs 0.4%, respectively; P = 0.013). The percentage of IL-17-producing CD4(+) T cells was equally increased in patients with and without MRI abnormalities (1.2% vs 1.1%, respectively; P = 0.81). These IL-17-producing CD4(+)T cells expressed the αβ T cell receptor but not the γδ T cell receptor, exhibited a memory phenotype and expressed CD161, but only sporadically expressed killer cell immunoglobulin-like receptor 3DL2 (KIR3DL2).
IL-17-producing CD4(+) T cells are increased in patients with early active axial SpA both with and without MRI abnormalities. This finding shows that the frequency of IL-17-producing CD4(+) T cells is enhanced in the early stages of disease.
在强直性脊柱炎(AS)患者中已观察到产生白细胞介素-17(IL-17)的CD4(+) T细胞数量增加。然而,尚不清楚这些CD4(+) T细胞在疾病早期是否已然存在,还是仅为疾病晚期的现象。因此,我们旨在通过测定这些患者中产生IL-17的CD4(+) T细胞的频率和表型,来研究产生IL-17的CD4(+) T细胞是否参与早期活动性中轴型脊柱关节炎(SpA),包括无影像学异常的患者。
采用流式细胞术分析31例符合国际脊柱关节炎评估协会标准的早期活动性 HLA-B27阳性中轴型SpA患者外周血单个核细胞的细胞因子产生情况和表面标志物表达,这些患者伴有或不伴有MRI异常,同时纳入21名健康对照者。
与健康对照相比,早期活动性中轴型SpA患者中产生IL-17的CD4(+) T细胞百分比增加(分别为均值1.1%对0.4%;P = 0.013)。有和无MRI异常的患者中产生IL-17的CD4(+) T细胞百分比均同样增加(分别为1.2%对1.1%;P = 0.81)。这些产生IL-17的CD4(+) T细胞表达αβ T细胞受体而非γδ T细胞受体,呈现记忆表型并表达CD161,但仅偶尔表达杀伤细胞免疫球蛋白样受体3DL2(KIR3DL2)。
在伴有和不伴有MRI异常的早期活动性中轴型SpA患者中,产生IL-17的CD4(+) T细胞均增加。这一发现表明,在疾病早期阶段,产生IL-17的CD4(+) T细胞频率升高。