Yoon Taejun, Ahn Sung Soo, Ko Eunhee, Song Jason Jungsik, Park Yong-Beom, Lee Sang-Won
BK21 Plus Project, Department of Medical Science, College of Medicine, Yonsei University, Seoul 03772, Republic of Korea.
Division of Rheumatology, Department of Internal Medicine, Yongin Severance Hospital, College of Medicine, Yonsei University, Yongin 16995, Republic of Korea.
J Clin Med. 2023 Nov 13;12(22):7059. doi: 10.3390/jcm12227059.
We investigated the IL-6 receptor (IL-6R) expression on the surface of T cells isolated from peripheral blood mononuclear cells (PBMCs) of microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA) patients and measured the serum soluble IL-6R (sIL-6R) levels in these patients. Sera and PBMCs were obtained from 51 patients with MPA ( = 32) and GPA ( = 19), with 25 patients having active disease (defined as a Birmingham Vasculitis Activity Score [BVAS] ≥ 5). The median age of patients was 67.0 years, and 52.9% were women. Serum IL-6 levels were significantly correlated with the BVAS (r = 0.384); however, IL-6R expression on the surface of T cells did not significantly differ based on disease activity. Meanwhile, IL-6R expression on the surface of stimulated CD4+ (median mean fluorescence intensity [MFI] 588.0 vs. 1314.8; < 0.001), CD4+CD25+ (MFI 853.3 vs. 1527.3; < 0.001), and CD4+CD45RO+ (MFI 679.5 vs. 1241.5; < 0.001) T cells was significantly reduced compared with unstimulated conditions. Conversely, patients with active disease exhibited a significantly higher median serum sIL-6R level than those with inactive disease (38.1 ng/mL vs. 34.7 ng/mL; = 0.029). These results imply that the trans-signalling IL-6 pathway may be more activated than the classical signalling pathway in patients with MPA and GPA, suggesting the therapeutic potential of targeting sIL-6R.
我们研究了从显微镜下多血管炎(MPA)和肉芽肿性多血管炎(GPA)患者的外周血单核细胞(PBMC)中分离出的T细胞表面白细胞介素-6受体(IL-6R)的表达情况,并测定了这些患者血清中可溶性IL-6R(sIL-6R)的水平。血清和PBMC取自51例MPA患者(n = 32)和GPA患者(n = 19),其中25例患者患有活动性疾病(定义为伯明翰血管炎活动评分[BVAS]≥5)。患者的中位年龄为67.0岁,52.9%为女性。血清IL-6水平与BVAS显著相关(r = 0.384);然而,T细胞表面的IL-6R表达并未因疾病活动度而有显著差异。同时,与未刺激状态相比,刺激后的CD4 + T细胞(中位平均荧光强度[MFI] 588.0对1314.8;P < 0.001)、CD4 + CD25 + T细胞(MFI 853.3对1527.3;P < 0.001)和CD4 + CD45RO + T细胞(MFI 679.5对1241.5;P < 0.001)表面的IL-6R表达显著降低。相反,活动性疾病患者的血清sIL-6R中位水平显著高于非活动性疾病患者(38.1 ng/mL对34.7 ng/mL;P = 0.029)。这些结果表明,在MPA和GPA患者中,IL-6的转信号通路可能比经典信号通路更活跃,提示靶向sIL-6R具有治疗潜力。