Decreased CD5+ B Cells in Active ANCA Vasculitis and Relapse after Rituximab
Decreased CD5+ B Cells in Active ANCA Vasculitis and Relapse after Rituximab
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DOI：
10.2215/cjn.03950412
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发表时间：
2013-03-01
影响因子：
9.8
通讯作者：
Nachman, Patrick H.
中科院分区：
文献类型：
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作者：
Bunch, Donna O'Dell;McGregor, JulieAnne G.;Nachman, Patrick H.
背景和目的B细胞在ANCA疾病发病机制中的重要性被以下发现所强调：在小鼠模型中单独的ANCA可以引起疾病以及利妥昔单抗作为ANCA-小血管炎（ANCA-SVV）的治疗的有效性。为了避免治疗引起的感染和不良事件，临床医生需要改进疾病活动性和即将复发的标志物，以指导利妥昔单抗治疗后的免疫抑制策略。设计、设置、参与者和测量研究了活动性ANCA-SVV和缓解期患者的B细胞表型。从2003年至2009年，对54例患者进行了4-99个月的纵向随访，并与68名健康对照者进行了比较。结果ANCA-SVV活动期患者CD 5（+）B细胞百分率较低，而缓解期患者CD 5（+）B细胞百分率与健康对照组无明显差异。利妥昔单抗治疗后，维持正常化%CD5（+）B细胞的患者中位复发时间为31个月，有或无维持免疫抑制。在B细胞重新增殖为低%CD5（+）B细胞或%CD5（+）B细胞急剧下降的患者中，低水平或未维持免疫抑制的患者复发更快（中位17个月）高于维持高水平口服维持免疫抑制剂的患者结论CD 5（+）B细胞作为人类B调节细胞表型的组成部分，是疾病活动、缓解和未来复发的有用指标，因此可指导利妥昔单抗治疗后的缓解维持治疗。Clin J Am Soc Nephrol 8：382-391，2013. doi：10.2215/CJN.03950412
Background and objectives B cell significance in ANCA disease pathogenesis is underscored by the finding that ANCA alone can cause disease in mouse models and by the effectiveness of rituximab as therapy in ANCA-small vessel vasculitis (ANCA-SVV). To avoid infections and adverse events from therapy, clinicians require improved markers of disease activity and impending relapse to guide immunosuppression strategies after rituximab treatment.Design, setting, participants, & measurements The B cell phenotype was investigated in patients with active ANCA-SVV and in remission. From 2003 to 2009,54 patients were followed longitudinally for 4-99 months and compared with 68 healthy controls. In a subset of 19 patients, the B cell immunophenotype was examined in samples after rituximab therapy.Results Patients with active ANCA-SVV had lower %CD5(+) B cells, whereas %CD5(+) B cells from patients in remission were indistinguishable from healthy controls. After rituximab, median time to relapse was 31 months in patients maintaining normalized %CD5(+) B cells, with or without maintenance immunosuppression. Among patients whose B cells repopulated with low %CD5(+) B cells or had a sharply declining %CD5(+) B cells, those who were on low or no maintenance immunosuppression relapsed sooner (median 17 months) than patients who were maintained on high levels of oral maintenance immunosuppression (29 months; P=0.002).Conclusions The %CD5(+) B cells, as a component of the human B regulatory cell phenotype, is a useful indicator of disease activity, remission, and future relapse, and thus may guide remission maintenance therapy after rituximab treatment. Clin J Am Soc Nephrol 8: 382-391, 2013. doi: 10.2215/CJN.03950412