Centre for Rheumatology, University College London, 5 University Street, London WC1E 6JF, UK.
Rheumatology (Oxford). 2012 Jul;51(7):1208-15. doi: 10.1093/rheumatology/ker526. Epub 2012 Feb 15.
To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels.
Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed. B-cell phenotype was examined in a subgroup of patients by flow cytometry.
Disease relapse was substantially delayed beyond B-cell repopulation, and early relapse was associated with a faster rate of repopulation. At relapse, B-cell numbers were significantly lower than at baseline in patients with high anti-dsDNA antibody levels (> 100 IU/ml) but not in patients with low anti-dsDNA antibody levels. Of the patients with high anti-dsDNA antibodies at baseline, levels fell significantly only in those patients who remained in remission after repopulation. Relapse with high anti-dsDNA antibody levels was associated with an increased percentage of IgD(-)CD27(hi) plasmablasts, whereas relapse with low anti-dsDNA antibody levels was accompanied by an increased percentage of IgD(-)CD27(-) B cells.
Anti-dsDNA antibody levels distinguished two patient groups, which differ in their B-cell number and phenotype at relapse following rituximab, and suggest that different B-cell pathologies exist in SLE. The data imply that B-cell numbers should be kept very low for a sustained period in patients with high dsDNA binding, therefore justifying a more aggressive regimen.
在系统性红斑狼疮（SLE）患者中，将 B 细胞再群体动力学与 B 细胞耗竭治疗后的复发相关联，并探讨复发率、B 细胞数量和表型的变化是否与抗双链 DNA（dsDNA）抗体水平相关。
61 例难治性 SLE 患者接受标准利妥昔单抗治疗方案。评估疾病活动度和 B 细胞数量的临床和血清学指标。通过流式细胞术检查患者亚组的 B 细胞表型。
疾病复发明显滞后于 B 细胞再群体，早期复发与再群体更快的速度相关。在复发时，高抗 dsDNA 抗体水平（>100 IU/ml）患者的 B 细胞数量明显低于基线水平，但低抗 dsDNA 抗体水平患者的 B 细胞数量则无明显变化。在基线时具有高抗 dsDNA 抗体的患者中，仅在再群体后仍处于缓解状态的患者中，抗体水平才显著下降。高抗 dsDNA 抗体水平的复发与 IgD(-)CD27(hi)浆母细胞百分比增加有关，而低抗 dsDNA 抗体水平的复发则伴随着 IgD(-)CD27(-)B 细胞百分比增加。
抗 dsDNA 抗体水平区分了两组患者，它们在利妥昔单抗治疗后复发时的 B 细胞数量和表型不同，提示 SLE 存在不同的 B 细胞病理。这些数据表明，在高 dsDNA 结合的患者中，B 细胞数量应保持非常低的水平持续一段时间，因此需要更积极的治疗方案。
