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

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.

A Comprehensive Review of HLA and Severe Cutaneous Adverse Drug Reactions: Implication for Clinical Pharmacogenomics and Precision Medicine

“…These findings are also supported by another study conducted in Thailand for non-leprosy patients [185]. Similar trends were also found with leprosy patients in other parts of Asia concluded that HLA-B*13:01 allele was a strong predictor for dapsone induced SCARs including SJS/TEN or DRESS [186][187][188][189]. However, such genetic associations were not identified in European, Caucasian, American, African, or Oceanic population indicating that HLA-B*13:01 allele associated dapsone induced SCARs were only prevalent in Asian population especially in China and Southeast Asia.…”

Genetics of Severe Cutaneous Adverse Reactions

“…By using GWAS approach, the susceptible gene of DHS was first found in Han Chinese with HLA-B * 13:01 (51), which mainly exists in Asians. The same result was validated in Koreans (52) and Indonesians (53). This gene was also susceptible in Thai with dapsone-induced SCARs (54), including DRESS and SJS/TEN (Table 1).…”

Sustained Actions in Combating Neglected Tropical Diseases during the COVID-19 Pandemic: Lessons Learned From the Leprosy Program in the Hyper-Endemic Area in Papua Province, Indonesia

“…It is a rare life-threatening reaction globally with a range of incidence of 2% to 12% with a fatality rate of 9.9% (18). Due to the dominant HLA-B*13:01 carrier in Papuan ethnic groups, the incidence rate of DHS is highly reported among leprosy patients (11%) treated by dapsone as the significant component in MDT (19). It is necessary to improve effective engagement between leprosy health workers or dermatologists and the undergoing treatment patients and release from treatment (RFT) patients.…”