INFLAMMATORY RESPONSE IN FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY (FSHD) - IMMUNOCYTOCHEMICAL AND GENETIC ANALYSES

To investigate the nature of the inflammatory response in facioscapulo humeral muscular dystrophy (FSHD), we analyzed mononuclear cells in mu scle sections obtained from 18 FSHD patients and 8 controls. Monoclona l antibodies reactive for T cells, T cell subsets, B cells, and NK cel ls were used for cell typing. Macrophages were identified by acid phos phatase reaction. The localization of perforin, granzyme A, MHC-I and -II, dystrophin, and oi-actinin antigens was also examined. We found t hat all FSHD patients, both familiar and sporadic cases, had greater a mounts of mononuclear cellular infiltrates in muscle than controls, in whose specimens only few extra vascular mononuclear cells were counte d. Seventy-two percent (13 of 18) of the patients had more than 50 inf lammatory mononuclear cells per 1000 muscle fibers, and 33% (6 of 18) patients had numerous inflammatory cells exceeding 600 per 1000 muscle fibers (1835 +/- 482 SE). Nonnecrotic fibers invaded by mononuclear c ells with either T8(+), perforin(+), or granzyme A(+) were not observe d in FSHD, while a few degenerating fibers were superficially invaded by T cells and macrophages. Occasional T cells were observed moving th rough the blood vessel wall. The increased number of necrotic fibers w as paralleled by an increased number of inflammatory cells (r = 0.783, P = 0.0001). Genetic analysis, using the probes p13E-11, pFR-1, D4S13 9, and D4S163, was done in 6 patients (3 familiar, 3 sporadic) who had numerous inflammatory infiltrates. These 6 patients had small (<28 kb ) EcoRI fragments associated with the disease, and the disease was lin ked to 4q35. These results suggest that, in chromosome 4-linked FSHD: (1) inflammatory changes in muscle are a common histological feature; (2) mononuclear cellular infiltrates may enhance muscle fiber damage; but (3) T-cell-mediated cytotoxicity directed against muscle fibers is unlikely. We speculate that the immune effector mechanism in FSHD is different from that in previously reported inflammatory myopathies and Duchenne muscular dystrophy. (C) 1995 John Wiley and Sons, Inc.