Objectives To explore phenotypic differences between individuals with sporadic inclusion body myositis (sIBM) who are seropositive for the NT5c1A antibody compared with those who are seronegative. Methods Cross-sectional clinical, serological and functional analysis in 25 consecutive participants with sIBM. Results All participants met criteria for clinically defined or probable sIBM. 18 of 25 participants with sIBM (72%) were seropositive for the NT5c1A antibody. No differences between median age and duration of illness between the two groups were seen. Females have higher odds of being seropositive (OR=2.30). Participants with seropositive sIBM took significantly longer to get up and stand (p=0.012). There were no significant differences between the two groups in terms of distance covered on a 6 min walk. Seropositive participants were more likely to require assistive devices such as a walker or wheelchair for mobility (OR=23.00; p=0.007). A number of secondary (exploratory) outcomes were assessed. NT5c1A seropositive sIBM cases had lower total Medical Research Council (MRC) sum score and MRC sum score on the right (p=0.03 and 0.02, respectively). Participants with the NT5c1A antibody were significantly more likely to have symptoms of dysphagia (OR=10.67; p=0.03) and reduced forced vital capacity (p=0.005). Facial weakness occurred in 50% of seropositive participants while it was only seen in 14% of seronegative participants. Conclusions Even though the small sample size limits definite conclusions, our cross-sectional study showed seropositivity to the NT5c1A antibody is associated with greater motor and functional disability in sIBM. The study also suggests more prominent bulbar, facial and respiratory involvement in individuals positive for NT5c1A antibodies.

Objective:To evaluate the therapeutic potential of targeting highly differentiated T cells in inclusion body myositis (IBM) patients, by establishing a high-resolution mapping of killer cell lectin-like receptor subfamily G member 1 (KLRG1+) within the T and NK cell compartments.Methods:Blood was collected from 51 IBM and 19 healthy age-matched donors. Peripheral blood mononuclear cells (PBMCs) were interrogated by flow cytometry using a 12-marker antibody panel. The panel allowed the delineation of naïve (Tn), central memory (Tcm), 4 stages of effector memory differentiation (Tem 1-4), and effector memory re-expressing CD45RA (TemRA) T cells, 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 cells were expanded in both the CD4+ and CD8+ T cell subpopulations in IBM patients. KLRG1 expression in CD8+ T cells increased with T cell differentiation with the lowest levels of expression in naïve T cells (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 IBM and healthy donors. IBM disease duration correlated with increased CD8+ T cell differentiation.Discussion:Collectively, our findings reveal that the selective expansion of blood KLRG1+ T cells in IBM patients is confined to the TemRA and Tem cellular compartments.