PMID- 34973118 OWN - NLM STAT- MEDLINE DCOM- 20220308 LR - 20220308 IS - 1867-0687 (Electronic) IS - 1708-8569 (Print) VI - 18 IP - 2 DP - 2022 Feb TI - Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome. PG - 109-119 LID - 10.1007/s12519-021-00489-y [doi] AB - BACKGROUND: Few studies have addressed the effects of human leukocyte antigen (HLA) alleles on different clinical sub-phenotypes in childhood steroid-sensitive nephrotic syndrome (SSNS), including SSNS without recurrence (SSNSWR) and steroid-dependent nephrotic syndrome/frequently relapse nephrotic syndrome (SDNS/FRNS). In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS. METHODS: A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system. RESULTS: Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS/FRNS (C3, P < 0.001; C4, P = 0.018). The average time to remission after sufficient initial steroid treatment in SDNS/FRNS was significantly longer than that in SSNSWR (P = 0.0001). Low level of C4 was further identified as an independent risk factor for SDNS/FRNS (P = 0.008, odds ratio = 0.174, 95% confidence interval 0.048-0.630). The HLA-A*11:01 allele was independently associated with SSNSWR and SDNS/FRNS (P = 0.0012 and P = 0.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS/FRNS. In addition, a mediating effect among HLA-I alleles (HLA-B*15:11, HLA-B*44:03 and HLA-C*07:06), C4 level and SDNS/FRNS was identified. CONCLUSIONS: HLA-I alleles provide novel genetic markers for SSNSWR and SDNS/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation. CI - (c) 2021. The Author(s). FAU - Lee, Hao AU - Lee H AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Wang, Li AU - Wang L AD - Department of Nephrology, Chengdu Women and Children Central Hospital, Chengdu, 610041, China. FAU - Ni, Fen-Fen AU - Ni FF AD - Department of Nephrology, Shenzhen Children's Hospital, Shenzhen, China. FAU - Yang, Xue-Ying AU - Yang XY AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Feng, Shi-Pin AU - Feng SP AD - Department of Nephrology, Chengdu Women and Children Central Hospital, Chengdu, 610041, China. FAU - Gao, Xiao-Jie AU - Gao XJ AD - Department of Nephrology, Shenzhen Children's Hospital, Shenzhen, China. FAU - Chi, Huan AU - Chi H AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Luo, Ye-Tao AU - Luo YT AD - Department of Statistics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Chen, Xue-Lan AU - Chen XL AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Yang, Bao-Hui AU - Yang BH AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Wan, Jun-Li AU - Wan JL AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Jiao, Jia AU - Jiao J AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Wu, Dao-Qi AU - Wu DQ AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Zhang, Gao-Fu AU - Zhang GF AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Wang, Mo AU - Wang M AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Yang, Hai-Ping AU - Yang HP AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. FAU - Chan, Han AU - Chan H AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. chenhancq@126.com. FAU - Li, Qiu AU - Li Q AUID- ORCID: 0000-0002-2481-7168 AD - Pediatric Research Institute, Department of Nephrology, Ministry of Education Key Laboratory of Child Development and Disorders, National Clinical Research Center for Child Health and Disorders, China International Science and Technology Cooperation base of Child development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, China. liqiu809@hospital.cqmu.edu.cn. LA - eng PT - Journal Article DEP - 20220101 PL - Switzerland TA - World J Pediatr JT - World journal of pediatrics : WJP JID - 101278599 RN - 0 (Steroids) SB - IM MH - Alleles MH - Genome-Wide Association Study MH - Humans MH - *Nephrotic Syndrome/diagnosis/drug therapy/genetics MH - Phenotype MH - Recurrence MH - Steroids/therapeutic use PMC - PMC8843916 OTO - NOTNLM OT - Human leukocyte antigen OT - Immunoregulation OT - Mediating effect OT - Steroid-sensitive nephrotic syndrome OT - Sub-phenotypes COIS- No financial or non-financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article. The authors have no conflict of interest to declare. EDAT- 2022/01/02 06:00 MHDA- 2022/03/09 06:00 PMCR- 2022/01/01 CRDT- 2022/01/01 12:04 PHST- 2021/09/14 00:00 [received] PHST- 2021/11/11 00:00 [accepted] PHST- 2022/01/02 06:00 [pubmed] PHST- 2022/03/09 06:00 [medline] PHST- 2022/01/01 12:04 [entrez] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.1007/s12519-021-00489-y [pii] AID - 489 [pii] AID - 10.1007/s12519-021-00489-y [doi] PST - ppublish SO - World J Pediatr. 2022 Feb;18(2):109-119. doi: 10.1007/s12519-021-00489-y. Epub 2022 Jan 1.