A Preliminary Study of Frequency and Clinical Relevance of Cytotoxic Peripheral CD4 and CD8 T Cells in Patients with Anti-MDA5 Positive Dermatomyositis

OBJECTIVES: Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5(+)DM) 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 MDA5(+)DM and this study aims to measure the frequency and clinical relevance of cytotoxic CD4 and CD8 T cells in this disease. METHODS: T cells expressing Perforin, Granzyme B (GZMB) and Granzyme K (GZMK) were analyzed by flow cytometry from peripheral blood of 19 patients with active MDA5(+)DM 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 MDA5(+)DM 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. RESULTS: Compared with HDs, patients with active MDA5(+)DM significantly had increased frequency of CD4 T cells, and reduced frequency of GZMK(+)GZMB(−) CD8 T cells. Furthermore, the frequency of GZMK(+)GZMB(−) CD8 T cells positively correlated with serum ferritin levels in active MDA5(+)DM patients. Notably, the patients in the Dead group of MDA5(+)DM had a significant higher frequency of GZMK(+)GZMB(−) CD4 and CD8 T cells. CONCLUSION: Substantial changes of cytotoxic T cell subsets are observed in active MDA5(+)DM patients. In addition, a high frequency of GZMK(+)GZMB(−) CD4 and CD8 T cells is associated with unfavorable prognosis in MDA5(+)DM. More studies are warranted to further explore the roles of cytotoxic T cells in MDA5(+)DM.