Jia Fengyun, Jiang Shan, Zhang Jiamin, Fu Qiong, Zhang Xiaoming, Ye Yan
The Center for Microbes, Development and Health, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai/University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Blood Group Reference Laboratory, Shanghai Blood Center, Shanghai 200051, China.
Rheumatol Immunol Res. 2022 Oct 20;3(3):136-142. doi: 10.2478/rir-2022-0022. eCollection 2022 Oct.
Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5DM) is an autoimmune disease frequently accompanied by rapidly progressive interstitial lung disease (RP-ILD) with high mortality. T cells are implicated in the pathogenesis of MDA5DM and this study aims to measure the frequency and clinical relevance of cytotoxic CD4 and CD8 T cells in this disease.
T cells expressing Perforin, Granzyme B (GZMB) and Granzyme K (GZMK) were analyzed by flow cytometry from peripheral blood of 19 patients with active MDA5DM and 19 age- and sex-matched healthy donors (HDs). The frequency of CD4 and CD8 T cells and the cytotoxic subsets were compared between patients with MDA5DM and HDs. Correlations within T cell subsets and between T cell subsets and clinical parameters of lactate dehydrogenase (LDH), ferritin, neutrophil-to-lymphocyte ratio (NLR), and Myositis Intention-to-Treat Index (MITAX) were evaluated.
Compared with HDs, patients with active MDA5DM significantly had increased frequency of CD4 T cells, and reduced frequency of GZMKGZMB CD8 T cells. Furthermore, the frequency of GZMKGZMB CD8 T cells positively correlated with serum ferritin levels in active MDA5DM patients. Notably, the patients in the Dead group of MDA5DM had a significant higher frequency of GZMKGZMB CD4 and CD8 T cells.
Substantial changes of cytotoxic T cell subsets are observed in active MDA5DM patients. In addition, a high frequency of GZMKGZMB CD4 and CD8 T cells is associated with unfavorable prognosis in MDA5DM. More studies are warranted to further explore the roles of cytotoxic T cells in MDA5DM.
抗黑色素瘤分化相关基因5阳性皮肌炎（MDA5DM）是一种自身免疫性疾病，常伴有快速进展性间质性肺病（RP-ILD），死亡率高。T细胞与MDA5DM的发病机制有关，本研究旨在测定该疾病中细胞毒性CD4和CD8 T细胞的频率及其临床相关性。
通过流式细胞术分析19例活动性MDA5DM患者和19例年龄及性别匹配的健康供者（HD）外周血中表达穿孔素、颗粒酶B（GZMB）和颗粒酶K（GZMK）的T细胞。比较MDA5DM患者和HD中CD4和CD8 T细胞的频率以及细胞毒性亚群。评估T细胞亚群内部以及T细胞亚群与乳酸脱氢酶（LDH）、铁蛋白、中性粒细胞与淋巴细胞比值（NLR）和肌炎意向性治疗指数（MITAX）等临床参数之间的相关性。
与HD相比，活动性MDA5DM患者的CD4 T细胞频率显著增加，而GZMK⁺GZMB⁺ CD8 T细胞频率降低。此外，活动性MDA5DM患者中GZMK⁺GZMB⁺ CD8 T细胞的频率与血清铁蛋白水平呈正相关。值得注意的是，MDA5DM死亡组患者的GZMK⁺GZMB⁺ CD4和CD8 T细胞频率显著更高。
在活动性MDA5DM患者中观察到细胞毒性T细胞亚群有显著变化。此外，GZMK⁺GZMB⁺ CD4和CD8 T细胞的高频率与MDA5DM的不良预后相关。需要更多研究进一步探索细胞毒性T细胞在MDA5DM中的作用。
