Nature Communications—Zhang Xiaoming's research group uses single-cell technology to reveal core immunological characteristics and treatment of highly lethal MDA5 antibody-positive dermatomyositis...

On October 29, the international academic journal Nature Communications published online a report entitled Single-cell profiling reveals distinct adaptive immune hallmarks in MDA5+ dermatomyositis with therapeutic The research paper of implications reveals the core immunological characteristics and new ideas
of targeted therapy of the highly lethal "anti-melanoma differentiation-associated gene 5-positive dermatomyositis" (MDA5+ DM).

MDA5+ DM is a rare but highly lethal autoimmune disease with positive MDA5 antibodies as its serological marker, and patients are prone to death
from rapidly progressive interstitial lung disease (RP-ILD).
At present, the core pathogenic mechanism of the disease has not been elucidated, and the lack of specific therapeutic targets is a major difficulty and hot spot
in the current autoimmune field.

Zhang Xiaoming's research group and Renji Rheumatology clinical team carried out a series of key research on MDA5+ DM, a refractory disease, using high-dimensional flow cytometry technology to measure peripheral immune cells in the early stage, dividing MDA5+ DM patients into high-risk and low-risk groups, and finding that CD8+ T cells have a high degree of activation, and the relevant paper was published in the authoritative journal of rheumatology Arthritis & Rheumatology (2022, 74:1822).

。 This study is a further deepening of the above research, and the immunological characteristics of peripheral blood and affected lung tissues in MDA5+ DM patients were analyzed by single-cell sequencing technology, focusing on the gene expression profiles and receptor repertoire characteristics of B and T lymphocytes related to acquired immunity, and verified by flow cytometry and multiple immunohistochemistry techniques
。 The study found that MDA5+ DM had the following core immunological characteristics: 1) peripheral plasma cells (also known as antibody-secreting cells ASC) and proliferative CD8+ T cells were significantly increased in patients with active MDA5+ DM; 2) overactivation of the type I interferon signaling pathway in the peripheral blood and lung tissues of the patient; 3) Peripheral ISG15+ CD8+ T cell elevation is a typical marker of active MDA5+ DM patients, and its elevation is closely related to
poor prognosis.
Based on the above research results, researchers propose personalized treatment strategies for patients, classify and precision patients according to the abnormal activation of T, B cells and type I interferon signaling pathways, including B cell targeted therapy (such as B cell clearance), T cell targeted therapy (such as calcineurin inhibitors, CNI), and interferon pathway targeted therapy (such as JAK inhibitors, JAKi), in order to improve the cure rate
of patients.

Legend: Identification of core immunological features in MDA5+ DM patients

Dr.
Ye Yan of Renji Hospital, Chen Zechuan and Jiang Shan, doctoral students of Shanghai Pasteur Institute, are the co-first authors of this paper, and Zhang Xiaoming, researcher of Shanghai Pasteur Institute, and Fuqiong, deputy chief physician of Renji Hospital, are the co-corresponding authors
of this paper.
The research was supported
by the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences (Pilot B), the Key R&D Program of the Ministry of Science and Technology, and the Shanghai Municipal Major Science and Technology Project.

Study Group Introduction:

Zhang Xiaoming's research group carries out human immunology research that is highly integrated with basic and clinical practice, and the main research directions are: 1) B-cell single-cell omics and innovative antibody research; 2) Multi-omics study of
diseases.
In the past 3 years, the leader of the research group has published 9 papers in SCI journals with impact factors of 15 or more as a corresponding author, including Cancer Discov, Ann Rheum Dis, Nat Commun, Arthritis Rheumatol and other journals; The research group is currently recruiting postdoctoral fellows and welcomes aspirants to join the research team (xmzhang@ips.
ac.
cn).

Full text link: https://doi.
org/10.
1038/s41467-022-34145-4