Benveniste O, Chérin P, Maisonobe T, Merat R, Chosidow O, Mouthon L, Guillevin L, Flahault A, Burland M C, Klatzmann D, Herson S, Boyer O
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, Service de Médecine Interne, and Laboratoire de Neuropathologie, Hôpital Pitié-Salpêtrière, Paris, France.
J Immunol. 2001 Sep 15;167(6):3521-9. doi: 10.4049/jimmunol.167.6.3521.
Polymyositis and dermatomyositis are diseases characterized by muscle weakness and muscle inflammatory infiltrates. Their pathogenesis remains unclear. A central role for endomysial autoaggressive CD8(+) T cells is suspected in polymyositis and for perivascular B cells in dermatomyositis. We compared the T cell repertoire of 10 polymyositis and 10 dermatomyositis patients by immunoscope, a method providing a global assessment of the T cell repertoire and a sensitive detection of clonal T cell expansions. Samples were analyzed qualitatively and quantitatively in the blood (unsorted cells and CD4(+) and CD8(+) cells) and in muscle infiltrates. Dramatic perturbations of the T cell repertoire were observed in the blood of polymyositis but not dermatomyositis patients (p < 0.0005), the latter being undistinguishable from controls. These perturbations were due to oligoclonal expansions of CD8(+) T cells and most blood clonal expansions were also found in muscle. These results indicate that the pathogenesis of polymyositis and dermatomyositis is different and reinforce the view that polymyositis but not dermatomyositis is an autoimmune CD8(+) T cell-mediated disease. Moreover, this method may be helpful for the differential diagnosis of polymyositis and dermatomyositis and for noninvasive follow-up of polymyositis patients.
多发性肌炎和皮肌炎是以肌肉无力和肌肉炎性浸润为特征的疾病。其发病机制尚不清楚。怀疑肌内膜自身攻击性CD8(+) T细胞在多发性肌炎中起核心作用，而血管周围B细胞在皮肌炎中起核心作用。我们通过免疫谱分析法比较了10例多发性肌炎患者和10例皮肌炎患者的T细胞库，该方法可对T细胞库进行全面评估，并能灵敏检测克隆性T细胞扩增。对血液（未分选细胞、CD4(+)和CD8(+)细胞）和肌肉浸润物进行了定性和定量分析。在多发性肌炎患者的血液中观察到T细胞库的显著紊乱，但皮肌炎患者未观察到（p < 0.0005），后者与对照组无差异。这些紊乱是由于CD8(+) T细胞的寡克隆扩增引起的，并且大多数血液中的克隆性扩增在肌肉中也能发现。这些结果表明，多发性肌炎和皮肌炎的发病机制不同，并强化了多发性肌炎而非皮肌炎是一种自身免疫性CD8(+) T细胞介导疾病的观点。此外，该方法可能有助于多发性肌炎和皮肌炎的鉴别诊断以及对多发性肌炎患者的无创随访。
