Department of Medicine, Rheumatology Unit, Landspitali University Hospital, 108, Reykjavík, Iceland.
Rheumatology (Oxford). 2013 May;52(5):847-55. doi: 10.1093/rheumatology/kes348. Epub 2013 Jan 3.
To investigate the long-term clinical, histological and serological affects of B-cell-depleting therapy (BCDT) in patients with LN refractory to conventional treatment.
Twenty-five patients, followed for a mean time of 36 months (9-95 months), were included. Renal disease activity was evaluated with the BILAG index and renal response was determined according to the LN European consensus statement. Renal biopsies were performed for histological evaluation at baseline and follow-up.
Partial response (PR) or complete renal response (CR) was observed in 22 of 25 after a median of 12 months. Sixteen patients achieved CR after a median of 24 months. Six patients experienced a renal relapse. Proteinuria decreased significantly (P = 0.0002) from baseline to 36 months. A noteworthy histological improvement was seen in nearly all patients with a significant reduction in activity index (P = 0.01). Longer depletion time and low baseline values of IgM were indicative of achieving clinical remission during the first year after treatment (P = 0.03 and P = 0.04, respectively).
In therapy-resistant LN, BCDT induced clinical and histological improvements in the majority of patients. Transition from PR to CR was mainly seen during the second year of follow-up. Patients with longer depletion time and low baseline levels of IgM were more likely to gain a faster remission, suggesting that the clinical benefit may be linked to suppression of autoreactive plasmablasts. Although formal evidence of BCDT in LN is lacking, our data may provide guidance to clinicians considering therapeutic options in patients with refractory LN.
探讨 B 细胞耗竭疗法（BCDT）对常规治疗无效的狼疮性肾炎（LN）患者的长期临床、组织学和血清学影响。
纳入 25 例患者，平均随访时间为 36 个月（9-95 个月）。采用 BILAG 指数评估肾脏疾病活动度，根据 LN 欧洲共识声明确定肾脏反应。基线和随访时进行肾活检进行组织学评估。
中位数 12 个月后，25 例患者中有 22 例观察到部分缓解（PR）或完全肾脏缓解（CR）。中位数 24 个月后，16 例患者达到 CR。6 例患者发生肾脏复发。蛋白尿从基线显著下降（P = 0.0002）至 36 个月。几乎所有患者均出现显著的组织学改善，活动指数显著降低（P = 0.01）。更长的耗竭时间和较低的基线 IgM 值提示在治疗后第一年达到临床缓解（P = 0.03 和 P = 0.04）。
在治疗抵抗性 LN 中，BCDT 诱导大多数患者的临床和组织学改善。从 PR 向 CR 的转变主要发生在随访的第二年。耗竭时间较长和基线 IgM 水平较低的患者更有可能更快获得缓解，这表明临床获益可能与抑制自身反应性浆母细胞有关。尽管缺乏 BCDT 在 LN 中的确切证据，但我们的数据可为考虑对难治性 LN 患者进行治疗选择的临床医生提供指导。
