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环磷酰胺治疗儿童激素依赖型肾病综合征的II类人类白细胞抗原(HLA)等位基因的回顾性队列分析

Retrospective Cohort Analysis of Class II Human Leukocyte Antigen (HLA) Alleles in Children With Steroid-Dependent Nephrotic Syndrome Treated With Cyclophosphamide.

作者信息

Javed Sehrish, Zubair Aasia, Qaiser Habib, Lanewala Ali Asghar A, Abbas Khawar, Musharraf Wajiha

机构信息

Pediatric Nephrology, Sindh Institute of Urology and Transplantation, Karachi, PAK.

Immunology, Sindh Institute of Urology and Transplantation, Karachi, PAK.

出版信息

Cureus. 2024 Dec 23;16(12):e76245. doi: 10.7759/cureus.76245. eCollection 2024 Dec.

Abstract

Background The role of specific human leukocyte antigen (HLA) alleles as a risk factor for susceptibility, protection, and response to cyclophosphamide (CYC) treatment has been studied in patients with idiopathic nephrotic syndrome (INS). This study investigates the association of class II HLA alleles and the treatment outcome in children with steroid-dependent nephrotic syndrome (SDNS) who were treated with CYC. Methods A total of 77 children who were diagnosed with SDNS and had received CYC at least a year before were enrolled. After obtaining informed consent from the parents, blood samples were collected to type the HLA class II locus (DR and DQ) using sequence-specific primers (SSP). An equal number of adult healthy controls (AHC) were included. Results The median age of the study participants at disease onset was five (IQ: 3-7) years with a male-to-female ratio of 1.48:1. The common HLA alleles found in the study cohort and controls were DRB17 45 (29%), DRB115 30 (19.5%), and DQB12 57 (37%), and DRB115 31(20%), DRB117 36 (23%), DQB16 42 (27%), and DQB1*2 38 (25%), respectively. Identification of a particular allele to predict a good or poor response was not statistically significant (p-value >0.05). Conclusion The study demonstrates the common HLA alleles in the cohort. However, a specific allele that can predict a good and poor response to CYP was not identified. Further large-scale, prospective multicenter studies are needed to identify such alleles to decide the use of CYC in the SDNS population judiciously.

摘要

背景

在特发性肾病综合征(INS)患者中,已对特定人类白细胞抗原(HLA)等位基因作为环磷酰胺(CYC)治疗易感性、保护性及反应性的危险因素的作用进行了研究。本研究调查了接受CYC治疗的激素依赖型肾病综合征(SDNS)儿童中II类HLA等位基因与治疗结局的关联。方法:共纳入77例诊断为SDNS且至少在一年前接受过CYC治疗的儿童。在获得家长知情同意后,采集血样,使用序列特异性引物(SSP)对HLA II类基因座(DR和DQ)进行分型。纳入数量相等的成年健康对照(AHC)。结果:研究参与者发病时的中位年龄为5岁(四分位间距:3 - 7岁),男女比例为1.48:1。研究队列和对照组中常见的HLA等位基因分别为DRB17 45(29%)、DRB115 30(19.5%)、DQB12 57(37%),以及DRB115 31(20%)、DRB117 36(23%)、DQB16 42(27%)和DQB1*2 38(25%)。鉴定特定等位基因以预测反应良好或不良无统计学意义(p值>0.05)。结论:本研究展示了队列中的常见HLA等位基因。然而,未鉴定出可预测对CYC反应良好或不良的特定等位基因。需要进一步开展大规模、前瞻性多中心研究以鉴定此类等位基因,从而明智地决定在SDNS人群中使用CYC。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/675a/11752407/a531d5fd128f/cureus-0016-00000076245-i01.jpg

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