Immunophenotyping of Inclusion Body Myositis Blood T and NK Cells.

BACKGROUND AND OBJECTIVES: To evaluate the therapeutic potential of targeting highly differentiated T cells in patients with inclusion body myositis (IBM) by establishing high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1+) within the T and natural killer (NK) cell compartments. METHODS: Blood was collected from 51 patients with IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naive T cells (Tn), central memory T cells (Tcm), 4 stages of effector memory differentiation T cells (Tem 1-4), and effector memory re-expressing CD45RA T cells (TemRA), as well as total and subpopulations of NK cells based on the differential expression of CD16 and C56. RESULTS: We found that a population of KLRG1+ Tem and TemRA were expanded in both the CD4+ and CD8+ T-cell subpopulations in patients with IBM. KLRG1 expression in CD8+ T cells increased with T-cell differentiation with the lowest levels of expression in Tn and highest in highly differentiated TemRA and CD56+CD8+ T cells. The frequency of KLRG1+ total NK cells and subpopulations did not differ between patients with IBM and healthy donors. IBM disease duration correlated with increased CD8+ T-cell differentiation. DISCUSSION: Our findings reveal that the selective expansion of blood KLRG1+ T cells in patients with IBM is confined to the TemRA and Tem cellular compartments.

Correlations of disease severity outcome measures in inclusion body myositis.

This study aimed to evaluate the correlation between various outcome measures used to assess disease severity and progression in inclusion body myositis (IBM) clinical trials. A cross-sectional study, involving 51 IBM patients meeting the European Neuromuscular Center (ENMC) 2011 criteria for clinically defined or probable IBM, was completed at the University of California, Irvine. Clinical details, demographic data, and functional data including timed get up (TGU), manual muscle testing, hand grip, pinch dynamometry, as well as IBM functional rating scale (IBMFRS), modified Rankin score, forced vital capacity (FVC), and modified ocular bulbar facial respiratory scale (mOBFRS) were collected on all patients. Descriptive statistics and Pearson's r correlation were performed to analyze the data. Age of the patient did not correlate with any of the outcome measures. Greater severity of IBMFRS scores correlated with longer disease duration as well as greater severity for FVC, strength outcomes, TGU, modified Rankin, and mOBFRS. Additionally, TGU strongly correlated with muscle strength measurements, modified Rankin, and mOBFRS. mOBFRS moderately correlated with IBMFRS, muscle strength, FVC, TGU and modified Rankin score. We demonstrate moderate to strong correlations among the disease severity outcome measures in this study.