Analysis Of The Correlation Between HLA Allele And Clinical Phenotype And Prognosis Of Children With Primary Nephrotic Syndrome

Difference of HLA allelefrequency in children with Primary nephrotic syndrome with different clinical phenotypesObjective:The study showed that children with Primary renal syndrome(PNS)with different clinical phenotypes have different clinical characteristics and genetic heterogeneity.Compared with healthy people,there are differences in HLA allele carrying frequency in children with SSNS,however,there are few reports on the characteristics of HLA allele carrying frequency in children with SSNS,SSNS-WR and SDNS/FRNS.This part aims to study the difference of HLA allele carrying frequency in children with PNS with different clinical phenotypes by using second-generation sequencing method based on the research of multi center and large samples.Methods:PNS children were from the Affiliated Children’s Hospital of Chongqing Medical University and kidney medicine in 2multi center hospitals,241 cases were in total,and the health control was from mygenomics database of Beijing Maijino Gene Technology Co.,Ltd.,1835 cases.Clinical data of PNS children were collected by outpatient and inpatient system;DNA separation,genotyping and quality control(QC)were performed by standard procedures;four digit resolution genotyping of HLA alleles was carried out by x HLA software;clinical characteristics,HLA-I/II allele distribution and expression frequency of children with PNS were statistically analyzed and compared.Results:1.compared with SSNS-WR,the level of C3 and C4 were lower(P< 0.05),and the first urinary protein transfer time of SDNS/FRNS children was significantly longer than SSNS-WR(P<0.0001);2.the first five alleles with the highest frequency in the six loci of HLA were the same in healthy population,SSNS,SSNS-WR and SDNS/FRNS;3 HLA-A-11:01,A*02:01 and B*15:02:01,B*15:02 were the most significant alleallegenes(P< 0.01),DQB1*06:02 and A*02:01 were the most significant protective allele(P < 0.01),A*11:01,B*15:02,DQB1*107:01,A*11:01,B*15:02,DQB1*107:01 were the SSNS-WR allelegenes(P < 0.01),DQB1*06:02 were the protective allele(P< 0.01);A*02:03 and A*11:01 were the susceptible allele(P < 0.01);A*02:03 and A*11:01were the susceptible allele(P < 0.01);A*02:03 and A*11:01 were the susceptible allele(P<0.01).However,there was no significant difference in HLA allele carrying frequency between SSNS-WR and SDNS/FRNS children;4 HLA-A*11:01 and HLA-DQB1*06:02 are alleles(P < 0.001)which are differentially expressed in PNS children(including SSNS,SSNS-WR and SDNS/FRNS).Among them,A*11:01 is highly expressed in PNS children and DQB1 *06:02 is low.Conclusion:1.There were differences in the first clinical indicators,therapeutic effects and long-term prognosis among children with PNS with different clinical phenotypes.Compared with SSNS-WR,SDNS/FRNS children had worse prognosis and higher risk of renal injury in the long term;2.The distribution of HLA-I/II alleles among the health control,SSNS,SSNS-WR and SDNS/FRNS groups was relatively average;3 Compared with the healthy control,there are differences in the carrying frequency of HLA alleles in children with PNS with different clinical phenotypes,and HLA-I is the main among the children in each group;4.there are some duplication of alleles expressed in children with different clinical phenotypes and health control.The correlation between HLA allele and clinical phenotype and prognosis of children with Primary nephrotic syndrome Objective: in the first part of the study,we have confirmed that PNS children have different clinical characteristics.Compared with the healthy control,there are differences in HLA allele carrying frequency between children with SSNS,SSNS-WR and SDNS/FRNS,and there are some duplication of alleles in children with PNS and healthy controls.Previous studies have shown that HLA-I/II alleles play an important role in antigen presentation,activation of immune response complex and regulation of immune homeostasis.Therefore,this part mainly discusses the relationship between HLA alleles and the possible mechanism of clinical characteristics and prognosis in children with PNS with different clinical phenotypes.Methods: To compare the effect of carrying / not carrying different alleles on clinical characteristics and prognosis of PNS children with different clinical phenotypes;taking gender and age as covariates,single factor and multi factor Logistic regression analysis were conducted to find out the risk factors related to SDNS/FRNS in PNS children;logistic regression analysis was used to explore the allele with frequency of >1%(frequency = 3) Because of the relationship with the risk factors of SDNS/FRNS,HLA alleles related to SDNS/FRNS risk were selected to be included in the analysis of the mediating effect.Results:1.In SSNS group,the first urinary protein transfer time of children with HLA-A* 02:01,A*30:01 and C*06:02 alleles was significantly shorter(P < 0.05);the level of Ig A in children with HLA-A* 01:01 was increased,on the contrary,the level of Ig A in children with DRB1 * 13:12,DPB1 * 107:01 and DPB1 * 131:01 decreased(P < 0.05);C3 and C4 water in children with HLA-A* 02:03,A* 03:01 and dpb1*131:01 were significantly reduced(P< 0.05)The results showed that the level of complement C3 and C4 in the patients with HLA-B*15:02 and DPB1*107:01 were higher in SSNS-WR group(P < 0.05);3.in SDNS/FRNS group,children with HLA-A*02:01,A*02:03 and A*11:01 alleles respectively affected the short time of urinary protein Yin transfer,higher TC level and higher onset age(P< 0.05);4.single factor and multivariate logistic regression analysis showed that C4 with lower level was an independent risk factor for children with PNS(P=0.041),5.logistic regression showed that HLA-B * 15:11,HLA-B * 44:03,HLA-C* 07:06 had significant correlation with C4(P< 0.05).Further analysis showed that there was a mediating effect among the three alleles,C4 and SDNS/FRNS.Conclusion:1.HLA alleles affect the clinical characteristics of PNS children,and there are some clinical heterogeneity in children with different clinical phenotypes;2.in PNS children with initial hormone sensitivity,lower C4 level may suggest that SDNS/FRNS may occur in the long term;3 HLA-B * 15:11,HLA-B*44:03 and HLA-C*07:06 may affect C4 level of PNS children and participate in regulating immune response,and indirectly affect long-term efficacy and prognosis.