31PClinico-sero-pathological and transcriptomic features of inclusion body myositis with T-cell large granular lymphocytic leukemia

Abstract

T-cell large granular lymphocytic leukemia (T-LGLL) is a rare indolent cytotoxic lymphocyte leukemia reported in 40–58% of inclusion body myositis (IBM) patients. We investigated the spectrum of myopathies in T-LGLL patients and compared clinicopathologic, laboratory, and transcriptomic features between IBM patients with and without T-LGLL. We retrospectively reviewed two Mayo Clinic cohorts: T-LGLL patients (2003–2018) evaluated for myopathies, and IBM patients (2016–2022) tested for T-LGLL by T-cell receptor gene rearrangement or flow cytometry. Among 447 T-LGLL patients, 13 (2.9%) had myopathies; IBM (n=7, 1.6%) was most common, followed by nonspecific inflammatory myopathy (n=3), nonspecific myopathy (n=2), and radiation-induced myopathy (n=1). Among 43 IBM patients, 9 (20.9%) had T-LGLL, with 5 diagnosed prior to the onset of weakness. Seven patients from the IBM cohort overlapped with the T-LGLL cohort. Clinical, pathological, and laboratory features were similar between IBM patients with and without T-LGLL, except for milder finger flexor weakness (median summated MRC 8.0 vs 6.0; p=0.01) and more frequent neutropenia (55.6% vs 0%; p<0.001) in the T-LGLL group. Two patients received immunotherapy for T-LGLL without improvement in myopathy. Transcriptomic analysis of IBM muscle biopsies showed that patients with T-LGLL had a more active immune profile, with upregulation of T-cell and macrophage markers, elevated levels of IFN-γ and IFN-γ–inducible genes, heightened cytokine activity, and enhanced immunoglobulin production. T-LGLL occurred in a minority of IBM patients in our cohort, less than previously reported. Despite similar clinicopathological features, transcriptomic data suggest IBM with T-LGLL reflects a more immunologically active disease subtype, which could have important implications for the development of future therapies.