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

OBJECTIVES: T-cell large granular lymphocytic leukemia (T-LGLL), reported in up to 58% of inclusion body myositis (IBM) patients, is a rare leukemia of cytotoxic or less commonly helper T cells. The range of myopathies in T-LGLL and the impact of coexisting T-LGLL in IBM are not well understood. Our objectives are to investigate the spectrum of myopathies in patients with T-LGLL and compare the clinical, serological, pathological, and transcriptomic features of IBM patients with and without T-LGLL. METHODS: We reviewed two Mayo Clinic cohorts: (1) T-LGLL patients evaluated for myopathies (2003-2018), and (2) IBM patients tested for T-LGLL via T-cell receptor gene rearrangement or flow cytometry (2016-2022). We also compared transcriptomic profiles of IBM muscle biopsies with and without T-LGLL. RESULTS: Of 447 T-LGLL patients, 13 (2.9%) had myopathies, IBM being the most common (n = 7). Of 43 IBM patients, 9 (20.9%) had T-LGLL, with 5 diagnosed prior to the onset of weakness. Clinical and pathological features were largely similar between IBM patients with and without T-LGLL, except for milder finger flexor weakness and more frequent neutropenia (55.6% vs. 0%, p < 0.001) in the T-LGLL group. However, transcriptomic analysis of muscle tissues revealed a more immunologically active profile, with upregulation of T-cell and macrophage markers, elevated levels of IFN-γ gene and IFN-γ-inducible genes, heightened cytokine activity, and enhanced immunoglobulin production in IBM patients with T-LGLL. INTERPRETATION: IBM is the most common myopathy in T-LGLL patients. While clinico-sero-pathological features were largely similar, transcriptomic differences suggest IBM with T-LGLL may represent a distinct, more immune-driven subtype.