Background Anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV)is a type of necrotizing vasculitis with poor prognosis,which is more severe in children.Classifying AAV patients may be helpful for diagnosis ...Background Anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV)is a type of necrotizing vasculitis with poor prognosis,which is more severe in children.Classifying AAV patients may be helpful for diagnosis and management.However,present classification criteria for pediatric AAV are developed mainly based on adults,which have limitations in clinical practice.In this study,we introduced an updated algorithm based on the European Medicines Agency(EMA)algorithm in conjunction with the American College of Rheumatology(ACR)/European Alliance of Associations for Rheumatology(EULAR)criteria.This new approach aims to resolve the issue of duplicate classification present in the 2022 ACR/EULAR criteria and to refine the existing EMA algorithm.Methods This study included 179 pediatric patients diagnosed with AAV across 17 centers in China.Patients were classified using the EMA algorithm,the ACR/EULAR criteria,and the EMA-ACR/EULAR algorithm.The Kappa value and Net Reclassification Index(NRI)were used to evaluate the classification performance of these criteria.Results According to the EMA algorithm,136(76.0%)patients were classified with microscopic polyangiitis(MPA)and 14(7.8%)with granulomatosis with polyangiitis(GPA),while 29(16.2%)remained unclassifiable.According to the ACR/EULAR criteria,145(81.0%)patients were classified with MPA,14(7.8%)with GPA,2(1.1%)with eosinophilic granulomatosis with polyangiitis(EGPA),and 4(2.2%)with both MPA and GPA,while 14(7.8%)remained unclassifiable.The EMA-ACR/EULAR algorithm classified 124 patients(69.3%)as MPA,26(14.5%)as GPA,and 2(1.1%)as EGPA,while 27(15.1%)were unclassified.The Kappa values between the EMA algorithm and ACR/EULAR criteria for GPA and MPA were 0.225[95%confidence interval(CI)0.000-0.456,P=0.003]and 0.357(95%CI 0.196-0.518,P<0.001).Compared to these two criteria,the EMA-ACR/EULAR algorithm demonstrated positive NRIs in the classification of both GPA(0.702,95%CI 0.258-1.146,P=0.002;0.54795%CI 0.150-0.944,P=0.007)and MPA(0.425,95%CI 0.209-0.642,P<0.001;0.519,95%CI 0.305-0.733,P<0.001).Conclusions The EMA-ACR/EULAR algorithm addresses the limitations of the 1990 ACR criteria within the EMA framework and resolves the issue of duplicate classification in the 2022 ACR/EULAR criteria.However,further research is necessary to validate the superiority of the EMA-ACR/EULAR algorithm in the clinical classification of pediatric AAV patients.展开更多
Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors...Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.展开更多
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(S...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.展开更多
基金sponsored by the National Key R&D Program of China(No.2021YFC2702002).
文摘Background Anti-neutrophil cytoplasmic antibody-associated vasculitis(AAV)is a type of necrotizing vasculitis with poor prognosis,which is more severe in children.Classifying AAV patients may be helpful for diagnosis and management.However,present classification criteria for pediatric AAV are developed mainly based on adults,which have limitations in clinical practice.In this study,we introduced an updated algorithm based on the European Medicines Agency(EMA)algorithm in conjunction with the American College of Rheumatology(ACR)/European Alliance of Associations for Rheumatology(EULAR)criteria.This new approach aims to resolve the issue of duplicate classification present in the 2022 ACR/EULAR criteria and to refine the existing EMA algorithm.Methods This study included 179 pediatric patients diagnosed with AAV across 17 centers in China.Patients were classified using the EMA algorithm,the ACR/EULAR criteria,and the EMA-ACR/EULAR algorithm.The Kappa value and Net Reclassification Index(NRI)were used to evaluate the classification performance of these criteria.Results According to the EMA algorithm,136(76.0%)patients were classified with microscopic polyangiitis(MPA)and 14(7.8%)with granulomatosis with polyangiitis(GPA),while 29(16.2%)remained unclassifiable.According to the ACR/EULAR criteria,145(81.0%)patients were classified with MPA,14(7.8%)with GPA,2(1.1%)with eosinophilic granulomatosis with polyangiitis(EGPA),and 4(2.2%)with both MPA and GPA,while 14(7.8%)remained unclassifiable.The EMA-ACR/EULAR algorithm classified 124 patients(69.3%)as MPA,26(14.5%)as GPA,and 2(1.1%)as EGPA,while 27(15.1%)were unclassified.The Kappa values between the EMA algorithm and ACR/EULAR criteria for GPA and MPA were 0.225[95%confidence interval(CI)0.000-0.456,P=0.003]and 0.357(95%CI 0.196-0.518,P<0.001).Compared to these two criteria,the EMA-ACR/EULAR algorithm demonstrated positive NRIs in the classification of both GPA(0.702,95%CI 0.258-1.146,P=0.002;0.54795%CI 0.150-0.944,P=0.007)and MPA(0.425,95%CI 0.209-0.642,P<0.001;0.519,95%CI 0.305-0.733,P<0.001).Conclusions The EMA-ACR/EULAR algorithm addresses the limitations of the 1990 ACR criteria within the EMA framework and resolves the issue of duplicate classification in the 2022 ACR/EULAR criteria.However,further research is necessary to validate the superiority of the EMA-ACR/EULAR algorithm in the clinical classification of pediatric AAV patients.
基金approved by the Ethics Committee of the Children’s Hospital of Chongqing Medical University(approval Number:149/2022)other enrolled centers.This study was registered at the Chinese Clinical Trial Registry(registered number:ChiCTR2000034203).
文摘Background Pediatric antineutrophil cytoplasmic antibody-associated vasculitis(AAV)is a life-threatening systemic vasculitis featured by liability to renal involvement.However,there are few studies on the risk factors and predictive models for renal outcomes of AAV in children.Methods Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively.The risk factors and predictive model of end-stage renal disease(ESRD)in AAV were explored.Results Renal involvement was the most typical manifestation(95.5%),and the crescent was the predominant pathological lesion(84.9%).The estimated glomerular filtration rate(eGFR)was evaluated in 114 patients,of whom 59.6%developed ESRD,and the median time to ESRD was 3.20 months.The eGFR[P=0.006,odds ratio(OR)=0.955,95%confidence interval(CI)=0.924–0.987]and the percentages of global glomerulosclerosis(pGGS;P=0.018,OR=1.060,95%CI=1.010–1.112)were independent risk factors for ESRD of renal biopsy.Based on the pGGS and eGFR at renal biopsy,we developed three risk grades of ESRD and one predictive model.The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades(P<0.001).Compared with serum creatinine at baseline,the predictive model had higher accuracy(0.86 versus 0.58,P<0.001)and a lower coefficient of variation(0.07 versus 0.92)in external validation.Conclusions Renal involvement is the most common manifestation of pediatric AAV in China,of which more than half deteriorates into ESRD.The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children.
基金funded by the China National Natural Science Foundation(No.81770713)China National Clinical Research Center Foundation(No.YBXM-2019-002).
文摘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.
