Characterization of key immune signatures of MDA5⁺ DM [IMAGE: IPS]

In a study published in Nature Communications on October 29, entitled “Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5⁺ dermatomyositis with therapeutic implications”, Professor Zhang Xiaoming’s group at the Institut Pasteur of Shanghai (IPS) of the Chinese Academy of Sciences (CAS) 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 file of autoimmune diseases.

Professor Zhang Xiaoming’s group at CAS’s IPS, together with the Department of Rheumatology, Renji Hospital, have carried out a series of studies on MDA5⁺ DM. With an in-depth study of peripheral immune cells by high dimensional flow cytometry, researchers classified the MDA5⁺ DM patients into two groups: high-risk and low-risk, which results were recently published in 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 pathways are observed in peripheral blood and in affected lungs from the MDA5⁺ DM patients; and 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 pathways.

For more information, please contact:

Zhang Xiaoming

E-mail: xmzhang@ips.ac.cn

Institut Pasteur of Shanghai (IPS),

Chinese Academy of Sciences

Source: Institut Pasteur of Shanghai (IPS),

Chinese Academy of Sciences