In the study published in the journal Nature Communications on October 29, entitled Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic implications, Prof. ZHANG Xiaoming’s group at the Institut Pasteur of Shanghai, the Chinese Academy of Sciences has reported the key immune hallmarks of MDA5+ DM and provided a potential basis for future tailored therapies.
Anti-melanoma differentiation-associated gene 5-positive dermatomyositis (MDA5+DM) is an infrequent autoimmune condition associated with high mortality. Patients with MDA5+ DM are characterized by anti-MDA5 autoantibody and prone to develop life-threatening rapidly progressive interstitial lung disease (RP-ILD). The aetiology and pathogenesis of MDA5+DM are largely unknown and targeted therapies are missing. This disease has posed a great challenge in the filed of autoimmune diseases.
Prof. ZHANG Xiaoming’s group at Institut Pasteur of Shanghai, together with Department of Rheumatology, Renji Hospital, have carried out a series of study on MDA5+ DM. With an in-depth study of peripheral immune cells by high dimensional flow cytometry, researchers have classified the MDA5+ DM patients into two groups: high-risk and low-risk, which has been recently published on Arthritis & Rheumatology (2022, 74:1822). The current study is a continued exploration of the previous study via single-cell RNA sequencing in peripheral B and T cells and in affected lung tissue samples. Other analyses including flow cytometry, multiplex immunohistochemistry and prognostic study were also utilized.
The study reveals that: 1) Antibody-secreting cells (ASCs) and proliferating CD8+ T cells are greatly expanded in the active MDA5+ DM patients compared with the control groups; 2) systemic overactivation of type I interferon signaling pathway are observed in peripheral blood and in affected lungs from the MDA5+ DM patients; 3) ISG15+ CD8+ T cell is a novel prognostic biomarker to predict unfavorable outcome in the MDA5+ DM patients. Considering the complex nature of MDA5+ DM, the researchers propose that a comprehensive immune cell and molecular profiling should be applied before a tailored therapy can be considered, for instance, B cell depletion to target B cells, calcineurin inhibitors to target T cells and Janus kinase inhibitors to target type I interferon signaling pathway.
Characterization of key immune signatures of MDA5+ DM. (Image by IPS)
Contact
ZHANG Xiaoming
E-mail: xmzhang@ips.ac.cn
