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利妥昔单抗与传统免疫抑制治疗对膜性狼疮性肾炎免疫沉积物的吸收作用比较。

Resorption of immune deposits in membranous lupus nephritis following rituximab vs conventional immunosuppressive treatment.

机构信息

Department of Medicine, Division of Rheumatology, Karolinska Institutet.

Rheumatology Unit.

出版信息

Rheumatology (Oxford). 2021 Jul 1;60(7):3443-3450. doi: 10.1093/rheumatology/keaa788.

Abstract

OBJECTIVES

Studies on repeat renal biopsies in membranous LN (MLN) are limited, and evaluation of treatment response is mainly based on proteinuria. EM of renal biopsies from rituximab (RTX)-treated MLN patients has revealed resorption of sub-epithelial ICs. Whether resorption phenomena are useful for treatment evaluation, or differs between treatment regimens is not known. We studied EM findings and clinical treatment response in MLN patients after RTX vs conventional immunosuppressive treatment.

METHODS

Twenty-four patients with MLN and renal biopsies performed before and after treatment were included in this retrospective observational study. Laboratory data were collected at both biopsy occasions. Seven patients had received RTX and 17 had received conventional treatment (CYC, MMF or AZA). Electron micrographs of renal tissue were scored using an arbitrary scale (0-3) for the level of sub-epithelial ICs, resorption of ICs and podocyte fusion.

RESULTS

Sub-epithelial ICs decreased after treatment, however not significantly and with no difference between treatments. The resorption phenomena increased after RTX (P = 0.028), but not after conventional therapy (P = 0.29). Six out of seven (86%) RTX-treated patients had increased resorption vs 7/17 (41%) after conventional therapies (P = 0.047). Clinical responders had more pronounced resorption of ICs vs non-responders (P = 0.022).

CONCLUSIONS

We report increased resorption of ICs in repeat renal biopsies in MLN, especially after RTX treatment. Increased resorption phenomena were associated with clinical response, suggesting that EM findings may be useful for treatment evaluation in MLN. Although of limited size, the study indicates that RTX is effective both clinically and at a tissue level.

摘要

目的

膜性肾病(MLN)重复肾活检的研究有限,治疗反应的评估主要基于蛋白尿。利妥昔单抗(RTX)治疗的 MLN 患者肾活检的 EM 显示,上皮下 IC 被吸收。吸收现象是否有助于治疗评估,或者在不同治疗方案之间是否不同尚不清楚。我们研究了 MLN 患者在接受 RTX 与传统免疫抑制治疗后的 EM 发现和临床治疗反应。

方法

本回顾性观察研究纳入了 24 例 MLN 患者,这些患者在治疗前后均进行了肾活检。在两次活检时均采集了实验室数据。7 例患者接受了 RTX 治疗,17 例患者接受了传统治疗(CYC、MMF 或 AZA)。使用任意评分(0-3)对肾组织的电子显微镜图像进行评分,用于评估上皮下 IC 水平、IC 吸收和足细胞融合。

结果

治疗后上皮下 IC 减少,但无统计学意义,且两种治疗方法之间无差异。RTX 治疗后吸收现象增加(P=0.028),但传统治疗后无变化(P=0.29)。7 例 RTX 治疗患者中有 6 例(86%)出现吸收增加,而 17 例传统治疗患者中有 7 例(41%)(P=0.047)。临床缓解者的 IC 吸收比非缓解者更明显(P=0.022)。

结论

我们报告了 MLN 重复肾活检中 IC 吸收增加,尤其是在接受 RTX 治疗后。吸收现象增加与临床反应相关,提示 EM 发现可能有助于 MLN 的治疗评估。尽管样本量有限,但该研究表明 RTX 在临床和组织水平均有效。

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