Arahata K, Ishihara T, Fukunaga H, Orimo S, Lee J H, Goto K, Nonaka I
National Institute of Neuroscience (NCNP), Tokyo, Japan.
Muscle Nerve Suppl. 1995;2:S56-66.
To investigate the nature of the inflammatory response in facioscapulohumeral muscular dystrophy (FSHD), we analyzed mononuclear cells in muscle sections obtained from 18 FSHD patients and 8 controls. Monoclonal antibodies reactive for T cells, T cell subsets, B cells, and NK cells were used for cell typing. Macrophages were identified by acid phosphatase reaction. The localization of perforin, granzyme A, MHC-I and -II, dystrophin, and alpha-actinin antigens was also examined. We found that all FSHD patients, both familiar and sporadic cases, had greater amounts of mononuclear cellular infiltrates in muscle than controls, in whose specimens only few extra vascular mononuclear cells were counted. Seventy-two percent (13 of 18) of the patients had more than 50 inflammatory 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 cells with either T8+, perforin+, or granzyme A+ were not observed in FSHD, while a few degenerating fibers were superficially invaded by T cells and macrophages. Occasional T cells were observed moving through the blood vessel wall. The increased number of necrotic fibers was paralleled by an increased number of inflammatory cells (r = 0.783, P = 0.0001). Genetic analysis, using the probes p13E-11, pFR-1, D4S139, 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 linked 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.
为了研究面肩肱型肌营养不良症（FSHD）中炎症反应的本质，我们分析了从18例FSHD患者和8例对照者获取的肌肉切片中的单核细胞。使用对T细胞、T细胞亚群、B细胞和NK细胞有反应性的单克隆抗体进行细胞分型。通过酸性磷酸酶反应鉴定巨噬细胞。还检测了穿孔素、颗粒酶A、MHC-I和-II、肌营养不良蛋白和α-辅肌动蛋白抗原的定位。我们发现，所有FSHD患者，无论是家族性还是散发性病例，其肌肉中的单核细胞浸润都比对照者多，在对照者的标本中仅计数到少量血管外单核细胞。72%（18例中的13例）的患者每1000条肌纤维中有超过50个炎性单核细胞，33%（18例中的6例）的患者有大量炎性细胞，每1000条肌纤维超过600个（1835±482 SE）。在FSHD中未观察到被T8 +、穿孔素 + 或颗粒酶A + 的单核细胞侵入的非坏死性纤维，而少数变性纤维被T细胞和巨噬细胞浅表侵入。偶尔观察到T细胞穿过血管壁。坏死纤维数量的增加与炎性细胞数量的增加平行（r = 0.783，P = 0.0001）。对6例（3例家族性、3例散发性）有大量炎性浸润的患者进行了基因分析，使用探针p13E - 11、pFR - 1、D4S139和D4S163。这6例患者有与疾病相关的小（<28 kb）EcoRI片段，且疾病与4q35连锁。这些结果表明，在与4号染色体连锁的FSHD中：（1）肌肉中的炎症变化是常见的组织学特征；（2）单核细胞浸润可能会加重肌纤维损伤；但（3）针对肌纤维的T细胞介导的细胞毒性不太可能。我们推测FSHD中的免疫效应机制与先前报道的炎性肌病和杜兴氏肌营养不良症中的不同。
