Revisiting the association between human leukocyte antigen and end-stage renal disease.

Naila Noureen,Mohammad Khalid,Nousheen Zaidi,Rimsha Munir,Farhad Ali Shah,Hina Usman,Jan Lisec,Xu-Jie Zhou

doi:10.1371/journal.pone.0238878

Abstract

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n = 497) and controls (n = 672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD, among which A*3_26 combination showed the highest strength of association (OR = 4.488, P≤ 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed that at least certain HLA alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, display a significant association with ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.

Highlights

A wide array of research works have indicated associations between human leukocyte antigen (HLA) status and various kidney diseases [1]
For HLA-A allele types, no significant differences were observed between the end-stage renal disease (ESRD) patients and the control group (Table 1)
For HLA-C allele types, again, no significant differences were observed between the ESRD patients and the control group (Table 1)

Summary

Introduction

A wide array of research works have indicated associations between human leukocyte antigen (HLA) status and various kidney diseases [1]. Few of these disorders are immune-mediated, while, in others, the pathogenesis is unclear or the relevance of HLA is not entirely understood. The end-stage renal disease (ESRD)–last stage of chronic renal failure–has become a global health problem [2] and has been investigated for HLA association [3,4,5]. In the majority of the previous works, ESRD patients waiting for kidney transplantation were examined.

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Conclusion