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Immune-Driven Expression in Inclusion Body Myositis With T-Cell Large Granular Lymphocytic Leukemia.

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Summary

Inclusion body myositis (IBM) is the most common myopathy in T-cell large granular lymphocytic leukemia (T-LGLL) patients. Transcriptomic analysis reveals IBM with T-LGLL may be a distinct, immune-driven subtype.

Keywords:
T‐cell large granular lymphocytic leukemiainclusion body myositistranscriptomic profiles

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Area of Science:

  • Hematology
  • Neurology
  • Immunology

Background:

  • T-cell large granular lymphocytic leukemia (T-LGLL) is a rare leukemia.
  • T-LGLL co-occurs in a significant percentage of inclusion body myositis (IBM) patients.
  • The spectrum of myopathies in T-LGLL and the impact of T-LGLL in IBM are not fully understood.

Purpose of the Study:

  • To investigate the spectrum of myopathies in T-LGLL patients.
  • To compare clinical, serological, pathological, and transcriptomic features of IBM patients with and without T-LGLL.
  • To determine if IBM with T-LGLL represents a distinct disease subtype.

Main Methods:

  • Retrospective review of two Mayo Clinic cohorts: T-LGLL patients with myopathies (2003-2018) and IBM patients tested for T-LGLL (2016-2022).
  • Analysis included T-cell receptor gene rearrangement or flow cytometry for T-LGLL detection.
  • Transcriptomic profiling of IBM muscle biopsies from patients with and without T-LGLL.

Main Results:

  • IBM was the most common myopathy (7/13) in T-LGLL patients.
  • 20.9% (9/43) of IBM patients had T-LGLL; 5 were diagnosed before weakness onset.
  • IBM patients with T-LGLL showed milder finger flexor weakness, more frequent neutropenia, and a more immunologically active muscle transcriptomic profile (T-cell/macrophage markers, IFN-γ, cytokines, immunoglobulin production).

Conclusions:

  • IBM is the predominant myopathy associated with T-LGLL.
  • Clinical and pathological features of IBM are largely similar with or without T-LGLL.
  • Transcriptomic data suggest that IBM with T-LGLL may represent a unique, immune-driven subtype of IBM.