Roccatello Dario, Sciascia Savino, Rossi Daniela, Solfietti Laura, Fenoglio Roberta, Menegatti Elisa, Baldovino Simone
Department of Clinical and Biological Sciences, Center of Research of Immunopathology and Rare Diseases, Coordinating Center of the Network for Rare Diseases of Piedmont and Aosta Valley, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.
Nephrology and Dialysis Unit, S. Giovanni Bosco Hospital and University of Turin, Turin, Italy.
Oncotarget. 2017 Jun 20;8(25):41764-41777. doi: 10.18632/oncotarget.16986.
Mixed cryoglobulinemia syndrome (MC) is a systemic vasculitis involving kidneys, joints, skin, and peripheral nerves. While many autoimmune, lymphoproliferative, and neoplastic disorders have been associated with this disorder, hepatitis C virus (HCV) is known to be the etiologic agent in the majority of patients. Therefore, clinical research has focused on anti-viral drugs and, more recently, on the new, highly potent Direct-acting Antiviral Agents (DAAs). These drugs assure sustained virologic response (SVR) rates >90%. Nevertheless, data on their efficacy in patients with HCV-associated cryoglobulinemic vasculitis are disappointing, possibly due to the inability of the drugs to suppress the immune-mediated process once it has been triggered.Despite the potential risk of exacerbation of the infection, immunosuppression has traditionally been regarded as the first-line intervention in cryoglobulinemic vasculitis, especially if renal involvement is severe. Biologic agents have raised hopes for more manageable therapeutic approaches, and Rituximab (RTX), an anti CD20 monoclonal antibody, is the most widely used biologic drug. It has proved to be safer than conventional immunosuppressants, thus substantially changing the natural history of HCV-associated cryoglobulinemic vasculitis by providing long-term remission, especially with intensive regimens.The present review focuses on the new therapeutic opportunities offered by the combination of biological drugs, mainly Rituximab, with DAAs.
混合性冷球蛋白血症综合征（MC）是一种累及肾脏、关节、皮肤和周围神经的系统性血管炎。虽然许多自身免疫性、淋巴增殖性和肿瘤性疾病都与该病症相关，但已知丙型肝炎病毒（HCV）是大多数患者的病原体。因此，临床研究主要集中在抗病毒药物上，最近则聚焦于新型、高效的直接抗病毒药物（DAA）。这些药物可确保持续病毒学应答（SVR）率超过90%。然而，关于它们对HCV相关冷球蛋白血症性血管炎患者疗效的数据却令人失望，这可能是因为一旦免疫介导过程被触发，这些药物无法抑制该过程。尽管存在感染加重的潜在风险，但传统上免疫抑制一直被视为冷球蛋白血症性血管炎的一线干预措施，尤其是在肾脏受累严重的情况下。生物制剂为更易于管理的治疗方法带来了希望，抗CD20单克隆抗体利妥昔单抗（RTX）是使用最广泛的生物药物。事实证明，它比传统免疫抑制剂更安全，通过实现长期缓解，尤其是采用强化治疗方案，极大地改变了HCV相关冷球蛋白血症性血管炎的自然病程。本综述重点关注生物药物（主要是利妥昔单抗）与DAA联合使用所带来的新治疗机会。
