全身性アミロイドーシスの分類・病態と治療

Diagnosis and Treatment in Systemic Amyloidosis

要旨　アミロイドーシスは，アミロイドと呼ばれる細線維性蛋白が全身の諸臓器へ沈着して，臓器障害を来す疾患の総称である．本疾患は前駆蛋白質の化学的性状と，全身性か限局性かにより分類される．限局性アミロイドーシスは沈着局所に障害を来すが，患者の生命予後は良好である．消化管，特に胃・十二指腸とS状結腸・直腸は限局性アミロイドーシスで侵されやすい部位である．全身性アミロイドーシスは，心臓，腎臓，消化管，末梢神経などを障害して，生命予後が不良な疾患である．しかし近年，本疾患では体内におけるアミロイド前駆蛋白の産生を阻止する治療により，いったん沈着したアミロイドが患者体内から退縮することが見い出され，根治療法への道が開けてきた．

　Systemic amyloidosis is characterized by the involvement of multiple organs and the presence of an amyloid precursor protein in serum. This disorder is classified into four major forms : immunoglobulin light chain-derived（AL）, reactive AA, dialysis-related（Aβ2）and hereditary transthyretin（ATTR）type. Heart, kidney, gastrointestinal tract and peripheral nerves are commonly affected by amyloid deposition in systemic amyloidosis and histopathological demonstration of amyloid deposits on any of affected organs is the first step leading to the diagnosis of this disease. Immunohistochemical analysis of amyloid protein on tissue amyloid deposits is necessary to make classification of the disease and DNA testing is also useful in the hereditary form. Amyloidosis had been considered to be an incurable disease but during the past decade several therapeutic approaches have been employed for amyloidosis patients with diverse pathogenetic backgrounds : intravenous large dose of melphalan accompanied by autologous peripheral blood stem cell transplantation for AL amyloidosis and liver transplantation for hereditary ATTR type amyloidosis. As a result some amyloidosis patients have been rescued and are now enjoying their own social lives. It is likely that recent advance in the research of amyloidosis has changed the concept of this disease.