Validation study of HLA-B*13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia

PLoS Negl Trop Dis. 2020 Oct 16;14(10):e0008746. doi: 10.1371/journal.pntd.0008746. eCollection 2020 Oct.

Abstract

Leprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, especially in Papua Island, leprosy is still a problem. Furthermore, there had been higher reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. Globally, DHS has a prevalence rate of 1.4% and a fatality rate up to 13%. The aim of this study is to validate HLA-B*13:01, a previously discovered biomarker for DHS in the Chinese population, as a biomarker for DHS in the Papua population.This is a case-control study of 34 leprosy patients who presented themselves with DHS (case subjects) and 52 leprosy patients without DHS (control subjects). Patients were recruited from 2 provinces: Papua and West Papua. DNA was extracted from 3 ml blood specimens. HLA-B alleles were typed using the gold-standard sequence based typing method. Results were then analysed using logistic regression and risk assessment was carried out. The results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio = 233.64 and P-value = 7.11×10-9, confirming the strong association of HLA-B*13:01 to DHS in the Papua population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95. HLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Biomarkers
  • Case-Control Studies
  • Clofazimine / administration & dosage
  • Dapsone / administration & dosage
  • Dapsone / adverse effects*
  • Drug Hypersensitivity / epidemiology
  • Drug Hypersensitivity / prevention & control*
  • Drug Therapy, Combination
  • Female
  • HLA-B13 Antigen / genetics*
  • Humans
  • Indonesia
  • Leprostatic Agents / administration & dosage
  • Leprostatic Agents / adverse effects*
  • Leprosy / drug therapy*
  • Logistic Models
  • Male
  • Rifampin / administration & dosage
  • Risk Assessment
  • Syndrome
  • Young Adult

Substances

  • Biomarkers
  • HLA-B13 Antigen
  • Leprostatic Agents
  • Dapsone
  • Clofazimine
  • Rifampin

Grants and funding

This work was supported by National Institute of Health Research and Development, Ministry of Health Republic of Indonesia (Grant no:2069.053.051 B, for authors HK, YM, YAS, TW, RT, AO), Genome Institute of Singapore, Agency for Science Technology and Research (Core Funding and Grant no: ETPL/17-GAP016-R20H, for authors AI, JL), National Key Research and Development Program of China (Grant no: 2016YFE0201500, for authors YS, HL, FZ). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.