Nakashima Ran, Mimori Tsuneyo
Department of Rheumatology and Clinical Immunology, Kyoto University Hospital.
Nihon Rinsho Meneki Gakkai Kaishi. 2013;36(2):71-6. doi: 10.2177/jsci.36.71.
Anti-MDA5 antibody is one of the dermatomyositis-specific autoantibodies and anti-MDA5-potsitive patients show characteristic clinical features, such as hypomyositis, high prevalence of acute/subacute interstitial pneumonia (A/SIP) with poor prognosis, hyperferritinemia and elevated hepatobiliary enzyme. We found that serum IL-6, IL-18, M-CSF and IL-10 were significantly higher and serum IL-12 and IL-22 were significantly lower in anti-MDA5-positive patients than in anti-MDA5-negative patients before treatment. Taking together these serological findings, we hypothesized that monocyte and macrophage activation may underlie in the pathophysiology of anti-MDA5-positive patients. They rarely survive after they become to need oxygenation, and so need to be treated as soon as possible once the diagnosis has been made. Intensive regimen of combined immunosuppressive therapy (high-dose corticosteroids, oral cyclosporin and intravenous cyclophosphamide (IVCY, 900-1000 mg/m(2) in every other week)) improved the survival rate of anti-MDA5-positive patients. Especially, the serum ferritin levels tended to go down about 14 days after IVCY, suggesting that IVCY might be a key drug in the treatment of anti-MDA5-positive A/SIP patients.
抗MDA5抗体是皮肌炎特异性自身抗体之一，抗MDA5阳性患者表现出特征性临床特征，如肌无力、急性/亚急性间质性肺炎（A/SIP）患病率高且预后差、铁蛋白血症及肝胆酶升高。我们发现，治疗前抗MDA5阳性患者血清IL-6、IL-18、M-CSF和IL-10显著升高，血清IL-12和IL-22显著降低。综合这些血清学发现，我们推测单核细胞和巨噬细胞激活可能是抗MDA5阳性患者病理生理学的基础。一旦需要氧疗，他们很少能存活，因此一旦确诊就需要尽快治疗。联合免疫抑制治疗的强化方案（大剂量皮质类固醇、口服环孢素和静脉注射环磷酰胺（IVCY，每两周900 - 1000 mg/m²））提高了抗MDA5阳性患者的生存率。特别是，静脉注射环磷酰胺后约14天血清铁蛋白水平有下降趋势，提示静脉注射环磷酰胺可能是治疗抗MDA5阳性A/SIP患者的关键药物。
