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.
Institute of Neurology, Department of Neurosciences, Catholic University of Rome, largo Gemelli 8, 00168 Rome, Italy.
Giovanni
G
Frisullo
Roberto
R
Frusciante
Viviana
V
Nociti
Giorgio
G
Tasca
Rosaria
R
Renna
Raffaele
R
Iorio
Agata Katia
AK
Patanella
Elisabetta
E
Iannaccone
Alessandro
A
Marti
Monica
M
Rossi
Assunta
A
Bianco
Mauro
M
Monforte
Pietro Attilio
PA
Tonali
Massimiliano
M
Mirabella
Anna Paola
AP
Batocchi
Enzo
E
Ricci
D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000150:complications / Q000276:immunology* / Q000473:pathology*; D009220:Myositis / Q000175:diagnosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index; D020825:T-Box Domain Proteins / Q000378:metabolism; D000098815:T-bet Transcription Factor
D016207:Cytokines; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor