CD8(+) T cells in facioscapulohumeral muscular dystrophy patients with inflammatory features at muscle MRI

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited disease, and although strongly suggested, a contribution of inflammation to its pathogenesis has never been demonstrated. In FSHD patients, we found by immunohistochemistry inflammatory infiltrates mainly composed by CD8(+) T cells in muscles showing hyperintensity features on T2-weighted short tau inversion recovery magnetic resonance imaging (T2-STIR-MRI) sequences. Therefore, we evaluated the presence of circulating activated immune cells and the production of cytokines in patients with or without muscles showing hyperintensity features on T2-STIR-MRI sequences and from controls. FSHD patients displaying hyperintensity features in one or more muscles showed higher CD8(+)pSTAT1(+), CD8(+)T-bet(+) T cells and CD14(+)pSTAT1(+), CD14(+)T-bet(+) cells percentages and IL12p40, IFNγ and TNFα levels than patients without muscles displaying hyperintense features and controls. Moreover, the percentages of CD8(+)pSTAT1(+), CD8(+)T-bet(+) and CD14(+)pSTAT1(+) cells correlated with the proportion of muscles displaying hyperintensity features at T2-STIR sequences. These data indicate that circulating activated immune cells, mainly CD8(+) T cells, may favour FSHD progression by promoting active phases of muscle inflammation.