Internal Medicine Department, Rheumatology and Clinical Immunology Unit, Faculty of Medicine, Cairo University, Giza, Egypt.
Center for Genomics, Zewail City of Science and Technology, Giza, Egypt.
EBioMedicine. 2018 Sep;35:106-113. doi: 10.1016/j.ebiom.2018.08.007. Epub 2018 Aug 20.
Mixed Cryoglobulinemic Vasculitis (MCV) is a prominent extra-hepatic manifestation of Hepatitis C virus (HCV) infection. HCV has been reported to cause B-cell disorders and genomic instability. Here, we investigated B-cell activation and genome stability in HCV-MCV patients receiving the direct antiviral agent, Sofosbuvir, at multiple centers in Egypt. Clinical manifestations in HCV-MCV patients were improved at the end of treatment (EOT), such as purpura (100%), articular manifestations (75%) and neuropathy (68%). Eighteen patients (56%) showed vasculitis relapse after EOT. BAFF and APRIL were higher at EOT and continued to increase one year following treatment onset. Chromosomal breaks were elevated at EOT compared to baseline levels and were sustained at 3 and 6 months post treatment. We report increased expression of DNA genome stability transcripts such as topoisomerase 1 and TDP1 in HCV-MCV patients after treatment, which continued to increase at 12 months from treatment onset. This data suggest that B-cell activation and DNA damage are important determinants of HCV-MCV treatment outcomes.
混合性冷球蛋白血症性血管炎 (MCV) 是丙型肝炎病毒 (HCV) 感染的一种重要的肝外表现。据报道，HCV 可引起 B 细胞疾病和基因组不稳定性。在这里，我们在埃及的多个中心研究了接受直接抗病毒药物 Sofosbuvir 治疗的 HCV-MCV 患者的 B 细胞激活和基因组稳定性。HCV-MCV 患者的临床表现在治疗结束时 (EOT) 得到改善，如紫癜 (100%)、关节表现 (75%)和神经病 (68%)。18 名患者 (56%) 在 EOT 后出现血管炎复发。BAFF 和 APRIL 在 EOT 时升高，并在治疗开始后一年持续升高。与基线水平相比，EOT 时染色体断裂增加，并在治疗后 3 个月和 6 个月持续存在。我们报告称，HCV-MCV 患者在治疗后 DNA 基因组稳定性转录本如拓扑异构酶 1 和 TDP1 的表达增加，并且从治疗开始后 12 个月持续增加。这些数据表明 B 细胞激活和 DNA 损伤是 HCV-MCV 治疗结果的重要决定因素。
