Citations

ABSTRACT 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.

Abstract Vasculitic neuropathy is caused by inflammatory destruction of nerve blood vessels resulting in nerve ischaemia. Nerve vasculitis can be divided into two categories based on vessel size: large-arteriole vasculitis (≥75 µm) and microvasculitis (&lt;75 µm). Herein, we characterize the clinical features of nerve large-arteriole vasculitis in comparison to nerve microvasculitis. This is a retrospective cohort study of patients evaluated and biopsied at Mayo sites between 2001 and 2020. We collected clinical and histopathological data from patients whose nerve biopsies were either diagnostic or highly suggestive of nerve vasculitis. Two hundred and seventy-eight cases were identified: 125 cases of large-arteriole vasculitis and 153 cases of microvasculitis. Nerve large-arteriole vasculitis presented with a more acute (50.4% versus 26.8%) versus chronic onset (33.6% versus 57.5%) than nerve microvasculitis (P = 0.0001). Nerve microvasculitis had longer mean time to diagnosis (10.5 versus 4.3 months; P &lt; 0.0001) and longer time to plateau (8.9 versus 3.5 months; P &lt; 0.0001). Nerve large-arteriole vasculitis typically presented as distal asymmetric polyneuropathy (48.0%), whereas nerve microvasculitis typically presented as radiculoplexus neuropathy/polyradiculoneuropathy (more proximal involvement of shoulder and thigh) (43.8%) (P &lt; 0.0001). Systemic autoimmune disease was more common in nerve large-arteriole vasculitis (70.4% versus 22.9%, odds ratio, 8.0; 95% confidence interval, 4.7–13.7; P &lt; 0.0001). Nerve microvasculitis was significantly related to non-systemic vasculitis (71% versus 23%, odds ratio, 7.9; 95% confidence interval, 4.6–13.6; P &lt; 0.0001). Nerve microvasculitis had more autonomic involvement (24.2% versus 7.2%, odds ratio, 4.1; 95% confidence interval, 1.9–8.9; P = 0.0002). Nerve large-arteriole vasculitis and nerve microvasculitis have different but overlapping clinical features. Nerve large-arteriole vasculitis usually presents with acute onset, distal asymmetric polyneuropathy, associated with other autoimmune diseases and systemic involvement. In contrast, nerve microvasculitis usually presents with a subacute/chronic onset, as radiculoplexus neuropathy/polyradiculopathy (distal and proximal pattern) with autonomic involvement, and is more often a form of non-systemic vasculitis.