Abstract: TH-PO1007
Associations of HLA Class II Alleles with Clinical Phenotype and Outcome in Patients with Primary Membranous Nephropathy: A Single Amino Acid Makes the Difference
Session Information
- Glomerular Diseases: Clinical, Outcomes, Trials - I
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Wang, Huaiyu, Peking University First Hospital, Peking University, Beijing, China
- Cui, Zhao, Peking University First Hospital, Peking University, Beijing, China
- Zhao, Minghui, Peking University First Hospital, Peking University, Beijing, China
Background
GWAS and HLA genotyping have revealed associations between HLA alleles and susceptibility to primary membranous nephropathy(pMN), but the associations with clinical phenotypes and kidney outcome are underinvestigated.
Methods
Patients with pMN were included. Associations between HLA alleles and clinical variants were analyzed by Logistic regression. Risk factors for kidney outcome were analyzed by Kaplan-Meier curve and COX regression. Structure of HLA molecules were modelled.
Results
DRB1*0301 was associated with higher level of PLA2R-Ab (OR=1.58, 95%CI 1.13-2.22, P=0.008). Although DRB1*1502 differs from DRB1*1501 by a single amino acid and was not risk allele for pMN, it was associated with lower eGFR both at baseline (OR=1.79, 95%CI 1.18-2.72, P=0.006) and last follow-up (OR=1.72, 95%CI 1.17-2.53, P=0.006), worse renal outcome (P=0.013) and higher risk of ESRD (HR=4.52, 95%CI 1.22-16.74, P=0.024). DRB1*1502 correlated to higher PLA2R-Ab level [161.4 (28.1, 268.0) vs. 36.3 (2.8, 130.5) U/mL, P=0.013] and showed interaction with DRB1*0301 for the variable(P=0.049). Homologous modelling showed the amino acid on position 86 is a valine in DRB1*1501, but a glycine in DRB1*1502, the latter facilitating the formation of a larger pocket 1 in the binding groove.
Conclusion
Our findings show that HLA genes control PLA2R antibody production and pMN severity and outcome. They additionally suggest that DRB1*1502 behaves like a modifier gene with a strong predictor value when associated with HLA risk alleles.
Figure 1. Renal survival curves in pMN patients.
Figure 2. Structure models of pocket 1 of DRB1*1501 and DRB1*1502.