Division of Clinical Immunology, Department of Translational and Precision Medicine, Sapienza University of Rome, Rome, Italy.
Laboratory affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome, Italy.
Liver Int. 2019 Apr;39(4):628-632. doi: 10.1111/liv.14053. Epub 2019 Feb 15.
BACKGROUND & AIMS: Hepatitis C virus (HCV)-related mixed cryoglobulinaemia vasculitis (MCV) is characterized by the expansion of rheumatoid factor-producing B-cell clones. The aim of this study was to assess whether B-cell clones may persist in these patients after the clearance of the virus with antiviral therapy, and whether their persistence influences clinical outcomes.
Forty-five HCV-cured MCV patients were followed up for a median of 18.5 (range 9-38) months after the clearance of HCV. Circulating B-cell clones were detected using flow cytometry either by the skewing of kappa/lambda ratio or by the expression of a V 1-69-encoded idiotype.
The clinical response of vasculitis was 78% complete, 18% partial and 4% null. However, cryoglobulins remained detectable in 42% of patients for more than 12 months. Circulating B-cell clones were detected in 18 of 45 patients, and in 17 of them persisted through the follow-up; nine of the latter patients cleared cryoglobulins and had complete response of vasculitis. Several months later, two of these patients had relapse of MCV.
B-cell clones persist in MCV patients long after HCV infection has been cleared but halt the production of pathogenic antibody. These 'dormant' cells may be reactivated by events that perturb B-cell homeostasis and can give rise to the relapse of cryoglobulinaemic vasculitis.
丙型肝炎病毒（HCV）相关的混合性冷球蛋白血症血管炎（MCV）的特征是产生类风湿因子的 B 细胞克隆的扩增。本研究旨在评估在抗病毒治疗清除病毒后，这些患者的 B 细胞克隆是否可能持续存在，以及它们的持续存在是否会影响临床结局。
45 例 HCV 治愈的 MCV 患者在 HCV 清除后中位数为 18.5 个月（范围 9-38 个月）进行了随访。通过流式细胞术检测循环 B 细胞克隆，通过κ/λ 比值的倾斜或 V 1-69 编码的独特型的表达来检测。
血管炎的临床反应为 78%完全缓解，18%部分缓解，4%无效。然而，42%的患者在超过 12 个月的时间里仍可检测到冷球蛋白。在 45 例患者中有 18 例检测到循环 B 细胞克隆，其中 17 例在随访期间持续存在；在这些患者中，有 9 例清除了冷球蛋白，血管炎完全缓解。几个月后，其中 2 例患者发生 MCV 复发。
在 HCV 感染清除后很长时间，MCV 患者的 B 细胞克隆仍持续存在，但停止产生致病性抗体。这些“休眠”的细胞可能会因破坏 B 细胞平衡的事件而被重新激活，并导致冷球蛋白血症性血管炎的复发。
