The rheumatology team of Renji Hospital reveals the core immunological characteristics of patients with anti-MDA5 antibody-positive dermatomyositis, which provides new ideas for precise targeted therapy

Recently, the rheumatology team of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine published a paper entitled "Single-cell profiling reveals distinct adaptive immune hallmarks in patients with MDA5+ dermatomyositis" online in the journal Nature Communications (impact factor IF: 17.
694).
in MDA5+ dermatomyositis with therapeutic implications), which provides new ideas
for the immunological pathogenesis and treatment strategies of anti-MDA5 antibody-positive dermatomyositis (MDA5+DM).

MDA5+DM is a special type of idiopathic inflammatory myopathy that is highly susceptible to rapidly progressive interstitial lung disease (RPILD), with approximately 40% of patients dying within 1 year of
onset.
The core pathogenic mechanism of the disease is still unknown, and there is a lack of specific and effective treatment methods, which is a hot spot and difficulty in clinical and basic research in the field of rheumatology
.

In this study, the clinical team of the Department of Rheumatology of Renji Hospital and the immunology research team of Zhang Xiaoming, a researcher at the Shanghai Pasteur Institute of the Chinese Academy of Sciences, analyzed the immunological characteristics of peripheral blood and lung tissues of MDA5+DM patients through single-cell sequencing technology, focusing on the gene expression profiles and receptor repertoire characteristics of T and B lymphocytes related to adaptive immunity, and verified them by multicolor flow cytometry and multiplex immunohistochemistry
。 The results found that the proportion of plasma cells (also known as antibody-secreting cells ASC) and proliferative CD8+ T cells in the peripheral blood of MDA5+DM patients with active disease increased significantly compared with the control group, indicating that the adaptive immune system was significantly activated
in the disease.
In addition, the type I interferon signaling pathway is overactive in the peripheral blood and lung tissues of patients, especially the proportion of CD8+ T cells expressing the interferon-inducing gene ISG15 is closely related to
the poor prognosis of the disease 。 Based on the above key cells and pathways related to MDA5+DM, the researchers proposed a new strategy for personalized detection and treatment of patients, evaluated the immune status of patients according to the activation of T and B cells and type I interferon signaling pathways, and combined with JAK inhibitors (JAKi) that have a targeted inhibition effect on interferon pathway and B cell differentiation and calcineurin inhibitors (CNI) targeting T cells, which may help improve treatment efficacy and improve patient survival
.

After more than 10 years of deep cultivation, the rheumatology team of Renji Hospital has accumulated rich clinical experience in the field of dermatomyositis and published a series of clinical research results: in 2019, Professor Ye Shuang led the publication of an innovative clinical study on the use of JAKi tofacitinib in the treatment of MDA5+DM combined with ILD in NEJM; In 2020, the rheumatology team published a FLAIR risk prediction model based on clinical indicators in the journal CHEST; Clinical stratification based on peripheral blood immunophenotyping and long-term follow-up and prognosis
of patients were reported in the journal Arthritis & Rheumatology and the journal Rheumatology in 2022.
This study focuses on the adaptive immunological characteristics of patients, which is not only of positive significance for pathogenesis research, but also provides new ideas
for exploring individualized targeted therapy.

Ye Yan, attending physician of the Department of Rheumatology of Renji Hospital, Chen Zechuan and Jiang Shan, doctoral students of the Pasteur Institute of the Chinese Academy of Sciences, are the co-first authors of the paper, and Fu Qiong, deputy chief physician of the Department of Rheumatology of Renji Hospital, and Zhang Xiaoming, researcher of the Pasteur Institute of the Chinese Academy of Sciences, are the co-corresponding authors
.

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