Kenji Koriyama

THE CONTINUOUS TREATMENT OF GENERALIZED MYASTHENIA GRAVIS WITH SMALL DOSES OF PREDNISOLONE WITH OR WITHOUT IMMUNOSUPPRESSANTS

重症筋無力症(以下MG)の病因として自己免疫説が注目されてきたにもかかわらず,本症に対しては副腎皮質ホルモンは一般に無効とされていた.最近になつて本剤の大量療法が難治全身型の本症に有効であることが見直されたが,なおその適応には種々の限界がある.わたくし達は胸腺摘出術(以下Thx)施行後の全身型MG8症例およびThx未施行の全身型MG8症例に対してprednisolone 5～10mg/dの少量持続療法を試みた.その結果, Thx施行後あるいは未施行のいずれの群でも60～75%の寛解あるいは著明改善例を認めることができ,効果発現時期は2～3カ月,寛解もしくは著明改善に到達するに要した期間は3～5カ月であつた.本療法開始後の臨床経過では一部の症例に1～2カ月以内に比較的不安定な時期がみられたが,これは抗cholinesterase剤(以下抗ChE剤)に対する神経筋接合部の反応性が増したためcholinergicに傾いたためであり,抗ChE剤を徐々に減量していくことによつて症状は好転し,この時期をすぎた3～5カ月頃には微量の抗ChE剤で安定した効果が得られるようになつた.本療法は少量であるところから従来の大量療法に較べ副作用はほとんどなく,一部の難治例に限られることなく軽症全身型MGにも応用できる点で適応の広い治療法であることが判明した.胸腺組織および末梢リンパ球にも検討を加え,本療法は胸腺(胚中心)ならびにリンパ球に働き,これらの異常を是正するとともに運動神経終板に結合する自己抗体の産生と機能を阻害すると考えられた.

SURFACE ULTRASTRUCTURE AND MICROVISCOSITY OF LYMPHOCYTE MEMBRANES IN MYASTHENIA GRAVIS

Myasthenia gravis (MG) is a disease caused by the impairment of neuromuscular junctions and characterized by high incidence of thymic involvement including thymoma or thymic hyperp1asia.l It has been demonstrated that the antibody against acetylcholine receptors (AChR) is present in sera of MG patienh2 The AChR has been found not only in synaptic membranes but also in thymic epithelial cells and thymic lymphocyte^.^ The antibody against AChR (anti-AChR antibody) is responsible for abnormality of neuromuscular j ~ n c t i o n . ~ Although direct evidence that peripheral lymphocytes of MG patients bear AChR is not found at present, abnormal findings such as decreased mitogenic activities,G higher response to AChR,7 and decreased T-cell in MG lymphocytes, and B-cell clone in the thymus were revealed. This evidence indicated that cell-mediated immune responses represented by lymphocytes play significant roles in the pathogenesis of MG. It is, therefore, of great interest to study the surface structures and functions of myasthenic lymphocytes resulting from the interaction between their receptors and anti-receptor antibodies since the impaired postsynaptic membrane is caused by the analogous interaction between AChR and the anti-AChR antibodies. The morphological alteration of cell surface can be observed by radioautography, ferritin or enzyme conjugated immunoelectron microscopy, immunoscanning electron microscopy and freeze-fractured technique. The functional changes in cell membranes can be evaluated by measuring the receptor activities and membrane microviscosity.8 We studied the relation between ultrastructural alterations and microviscosity of the cell membrane in the peripheral blood lymphocytes from MG patients, from the viewpoint that the alteration of MG lymphocyte membranes may represent the impairment of postsynaptic membranes in MG.