胸腺異常と重症筋無力症

Thymic Abnormalities in Patients with Myasthenia Gravis

はじめに

　重症筋無力症（myasthenia gravis：MG）患者に胸腺異常が認められることは，今から100年以上前には既に知られていた事実である^1－5）。MGが主に骨格筋アセチルコリン受容体（acetylcholine receptor：AChR）に対する抗体を介する自己免疫疾患であると判明（1973年)^6）後，この自己免疫病態とMG胸腺の関連について多くの研究が行われてきた。総じて言えば，MGの発病と持続に必要な免疫病態の一部には胸腺が関与している。しかし，その関与の仕方，程度は，胸腺組織型や発症年齢，さらには発症後の期間によっても異なる。実際には，胸腺摘除により病勢が沈静化し完全寛解を得るような例は少ない^7－9）。

　MGの胸腺異常は，若年発症MG（early onset MG：EOMG，発症年齢＜50歳，＜40歳とする意見もある）例の約半数にみられる過形成胸腺（thymus exhibiting lymphofollicular hyperplasia：TLFH）と，MG例全体の10～15％にみられる胸腺腫（thymoma）である^10－11）。高齢発症MG（late onset MG：LOMG，発症年齢≧50歳）非胸腺腫例の萎縮胸腺は，正常対照例の萎縮胸腺と差はない^12，13）。本稿では，EOMGのTLFH，胸腺腫，LOMG非胸腺腫例の萎縮胸腺のそれぞれについて，MG病態との関連を概説し，胸腺摘除の臨床的な意義についても触れる。

Abstract

　Thymic abnormalities were first noticed at autopsies of patients with myasthenia gravis (MG) more than 100 years ago.　The thymus is believed to play an important role in the pathogenesis of MG, an autoimmune disease mediated by antibodies against the acetylcholine receptor (AChR) of skeletal muscles.　Production of these antibodies in B cells is T cell dependent.　T cells potentially specific for AChR are probably generated in the thymus via nontolerogenic thymopoiesis by an aberrant function of thymic epithelial cells.　However, generation of these AChR-specific T cells is not the cause of MG, because these cells are also found in healthy individuals.　The pathogenetic step in MG involves the activation of these potentially AChR-specific T cells; this activation is the trigger to develop the disease and a therapeutic target.　The intra-thymic activation of AChR-specific T cells is probably limited to particular types of MG patients: those with early-onset MG in whom the thymus exhibits lymphofollicular hyperplasia (TLFH) and a few patients in whom MG is associated with a thymoma.　The majority of thymomas and atrophic thymuses of patients with late-onset MG, an increasingly common condition, do not exhibit this T cell-activation process.

　In this paper,we review the available literature on thymic changes (TLFH,thymoma,and atrophic thymus) and the relationship of these changes to the pathogenesis of MG.