Pathogenic T-cell signature identified in myasthenia gravis

A Swiss in-depth analysis of the immune dysregulation underlying myasthenia gravis (MG) provided valuable insight into potential disease pathogenesis and the role of the thymus in connection with disease severity.

The auto-antigen and effector mechanisms of MG are well defined, but the cellular and molecular drivers of this auto-immune disease remain elusive. Dr Bettina Schreiner (University of Zürich, Switzerland) presented a study which employed high-dimensional single-cell mass and flow cytometry in a cohort of mainly newly diagnosed MG patients in order to:

• screen the peripheral blood for an MG disease signature;
• identify map correlations between immune clusters and MG severity; and
• create a leukocyte map of the diseased thymus [1].

B-cell frequencies were found to be highly increased in the inflamed thymus, but not in the peripheral blood of MG patients. A comprehensive immune map identified a decrease of inflammatory circulating memory T-helper subsets such as Th_GM and Th_CD103 cells that migrated to the inflamed thymus. Circulatory TNF-producing Th_CD103 cells populated the diseased thymus, were reduced in the blood of MG patients, and were strongly inversely correlated with clinical disease severity of MG patients.

After surgical removal of the thymus, both of these signature T-helper subsets seemed to rebound in the blood –underlining their role as cellular markers of disease activity– and were effectively targeted by azathioprine treatment.

1. Ingelfinger F, et al. Single-cell profiling of myasthenia gravis identifies a pathogenic T cell signature. OPR-209, EAN 2021 Virtual Congress, 19–22 June.

 

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Posted on 18 August 202118 August 2021