Abstract:

OBJECTIVE: To elucidate the common and distinct clinical features of immune-mediated necrotising myopathy (IMNM), also known as necrotising autoimmune myopathy associated with autoantibodies against signal recognition particle (SRP) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR).
METHODS: We examined a cohort of 460 patients with idiopathic inflammatory myopathies (IIMs) through a muscle biopsy-oriented registration study in Japan. Study entry was strictly determined by the comprehensive histological assessment to exclude other neuromuscular disorders. Anti-SRP and anti-HMGCR antibodies were detected by RNA immunoprecipitation and ELISA, respectively.
RESULTS: Of 460 patients with IIM, we diagnosed 73 (16%) as having inclusion body myositis (IBM). Of 387 patients with IIMs other than IBM, the frequencies of anti-SRP and anti-HMGCR antibodies were 18% and 12%, respectively. One patient had both autoantibodies. Severe limb muscle weakness, neck weakness, dysphagia, respiratory insufficiency and muscle atrophy were more frequently observed in patients with anti-SRP antibodies than in those with anti-HMGCR antibodies. Serum creatine levels were markedly higher in the patients with autoantibodies than in those without. Histology was characterised by necrosis and regeneration of muscle fibres and was consistent with IMNM except in 1 HMGCR-positive IBM patient. Most patients were initially treated with corticosteroids; however, additional immunosuppressive drugs were required, especially in the patients with anti-SRP antibodies. Rates of unsatisfactory neurological outcome were similar in the 2 autoantibody groups.
CONCLUSIONS: Anti-SRP antibodies are associated with severe neurological symptoms, more so than are anti-HMGCR antibodies. Although these autoantibodies are independent serological markers associated with IMNM, patients bearing either share common characteristics.

日本語要旨:

自己免疫介在性壊死性ミオパチー(iNM)に関連する自己抗体として抗SRP抗体と抗HMGCR 抗体が知られているが、両者がもたらす臨床病理学的な差異は明らかではなく、本研究はそれを明らかにすることを目的とした。2010 - 2014年に筋炎統合的診断研究プロジェクトに登録された特発性炎症性筋疾患症例 460例のうち、臨床病理学的にiNMと診断された例は177例であった。うち抗 SRP抗体陽性例は69例(39%)、抗HMGCR 抗体陽性例は46例(26%)であった。これらの症例を対象に臨床病理像を比較した。抗SRP 抗体陽性例では重度の筋力低下、筋萎縮、頚部筋力低下、嚥下障害、呼吸障害、間質性肺病変の頻度が有意に高く、一方、抗HMGCR抗体陽性例ではスタチン製剤の使用、細胞膜上へのMAC (C5b-9)沈着が高頻度であった。 本研究は抗SRP抗体と抗HMGCR抗体の臨床病理像を過去最大規模の症例数で解析し、両者の相違点を世界に先駆けて報告した。 尚、この内容は同号のEditorialで注目論文として取り上げられた。