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磷脂酶 A2 受体基因多态性联合免疫球蛋白 G 亚类在肾组织中对膜性肾病的临床预测价值。

Clinical Predictive Value of Phospholipase A2 Receptor Gene Polymorphism Combined with Subclass of Immunoglobulin G in Renal Tissues for Membranous Nephropathy.

出版信息

Altern Ther Health Med. 2023 Oct;29(7):418-423.

PMID:37535917
Abstract

CONTEXT

Idiopathic membranous nephropathy (IMN) is a common pathologic type of nephrotic syndrome, and the level of the M-type phospholipase A2 receptor (PLA2R) antibody can serve as one index for predicting its progression and prognosis. However, patients with the same level can show great differences in their responses and prognoses.

OBJECTIVES

The study aimed to explore the relationship between a PLA2R gene polymorphism combined with an immunoglobulin G (IgG) subclass in renal tissues and patients' responses to immunosuppressive therapy, to determine the clinical prognosis for IMN patients.

DESIGN

This is a prospective study. Patients with new onset membranous nephropathy who need treatment were selected and grouped according to the curative effect after 6 months of treatment.

SETTING

The study took place at the First Affiliated Hospital of Ningbo University, Ningbo, China.

PARTICIPANTS

Participants were 60 patients with IMN, who had been admitted in the hospital between January 1, 2021 and June 30, 2022.

INTERVENTION

Participants first received standard immunosuppressive therapy for six months. The research team then clinically divided participants into two groups: (1) a remission group with 32 participants and (2) a nonremission group with 28 participants.

OUTCOME MEASURES

The research team: (1) compared the groups, summarizing the demographic and clinical differences between the groups, (2) compared the PLA2R antibody titers at baseline and postintervention between the groups, (3) analyzed the genotyping of the PLA2R single nucleotide polymorphisms (SNPs) rs35771982 and rs4664308 loci as well as the human leukocyte antigen (HLA)-DQA1 SNP rs2187668 locus, and (4) compared the subclass IgG and PLA2R depositions in the renal tissues between the groups.

RESULTS

Compared with the remission group, the nonremission group included significantly more males (P < .05), was significantly older (P < .05), had significantly more participants with a BMI of >25 (P < .05), and included significantly more participants with a positive IgG3 (P < .01) than the remission group. The remission group's PLA2R antibody titers at baseline and postintervention weren't significantly different from those of the nonremission group. Postintervention, 24 participants in the remission group had a negative conversion of PLA2R antibodies, and 22 in the nonremission group had a negative conversion. The genotyping of the PLA2R SNP rs4664308 and the HLA-DQA1 SNP rs2187668 loci showed no relationship to the remission rate. The GC genotype on the PLA2R SNPrs35771982 locus may be a risk factor for a poor prognosis for IMN patients. Moreover, the patients with a positive IgG3 in the renal tissues and the GC genotype on the PLA2R SNPrs35771982 locus exhibited a poor response to immunosuppressive therapy and could need intensive treatment.

CONCLUSIONS

The PLA2R gene polymorphism combined with the IgG subclass can predict the sensitivity of IMN patients to immunosuppressive therapy.

摘要

背景

特发性膜性肾病(IMN)是肾病综合征的一种常见病理类型,M 型磷脂酶 A2 受体(PLA2R)抗体水平可作为预测其进展和预后的指标之一。然而,具有相同水平的患者在反应和预后方面可能存在很大差异。

目的

本研究旨在探讨 PLA2R 基因多态性与肾组织 IgG 亚类联合与患者对免疫抑制治疗的反应之间的关系,以确定 IMN 患者的临床预后。

设计

这是一项前瞻性研究。选择新诊断的需要治疗的膜性肾病患者,并根据治疗 6 个月后的疗效进行分组。

地点

中国宁波大学附属第一医院。

参与者

60 例 IMN 患者,于 2021 年 1 月 1 日至 2022 年 6 月 30 日期间在医院就诊。

干预措施

患者首先接受标准的免疫抑制治疗 6 个月。研究团队随后将患者临床分为两组:(1)缓解组 32 例,(2)未缓解组 28 例。

观察指标

(1)组间比较,总结组间的人口统计学和临床差异,(2)比较组间基线和治疗后 PLA2R 抗体滴度,(3)分析 PLA2R 单核苷酸多态性(SNP)rs35771982 和 rs4664308 以及人类白细胞抗原(HLA)-DQA1 SNP rs2187668 位点的基因分型,(4)比较组间肾组织 IgG 亚类和 PLA2R 沉积情况。

结果

与缓解组相比,未缓解组男性比例显著更高(P<0.05),年龄显著更大(P<0.05),BMI>25 的患者比例显著更高(P<0.05),且 IgG3 阳性的患者比例显著更高(P<0.01)。缓解组的 PLA2R 抗体滴度在基线和治疗后均与未缓解组无显著差异。治疗后,缓解组 24 例 PLA2R 抗体转为阴性,未缓解组 22 例转为阴性。PLA2R SNP rs4664308 和 HLA-DQA1 SNP rs2187668 位点的基因分型与缓解率无关。PLA2R SNP rs35771982 位点的 GC 基因型可能是 IMN 患者预后不良的危险因素。此外,肾组织中 IgG3 阳性和 PLA2R SNP rs35771982 位点 GC 基因型的患者对免疫抑制治疗反应不佳,可能需要强化治疗。

结论

PLA2R 基因多态性与 IgG 亚类联合可预测 IMN 患者对免疫抑制治疗的敏感性。

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