Validation Study of HLA-B*13:01 as a Biomarker of Dapsone Hypersensitivity Syndrome in Leprosy Patients in Indonesia

Abstract

ABSTRACTImportanceLeprosy is a stigmatizing, chronic infection which degenerates the nervous system and often leads to incapacitation. Multi-drug therapy (MDT) which consists of dapsone, rifampicin and clofazimine has been effective to combat this disease. In Indonesia, leprosy is still a problem. Furthermore, there had been reports of Dapsone Hypersensitivity Syndrome (DHS) which also challenges leprosy elimination in certain aspects. HLA-B*13:01 has been found to be associated with DHS and prospective screening has proven its ability to prevent DHS in the Chinese population, but has not been validated in Indonesians.ObjectiveTo validate HLA-B*13:01 as a biomarker for DHS in the Indonesian population.DesignThis is a case-control study.SettingPopulation-based, multi-district recruitment from primary care centers in two of the top 3 most prevalent provinces in Indonesia, Papua and West Papua.ParticipantsLeprosy patients who presented themselves with DHS were recruited as case subjects (34 cases) and leprosy patients without DHS were recruited as control subjects (52 controls).ExposureLeprosy patients who had undergone multi-drug treatment for leprosy under the standard WHO guideline, consisting of rifampicin, dapsone and clofazamine.Main Outcome and MeasuresThe association of HLA-B*13:01 to DHS based on difference in allele frequencies between cases and controls. HLA-B alleles were typed using the gold-standard Sequence Based Typing method. Results were analyzed using logistic regression and risk assessment was carried out.ResultsThe results of HLA-typing showed that HLA-B*13:01 was the most significant allele associated with DHS, with odds ratio=247.6 and P-value=4.81E-9, confirming the strong association of HLA-B*13:01 to DHS in the Indonesian population. The sensitivity of this biomarker is 91.2% and specificity is 96.2%, with an area under the curve of 0.95.Conclusions and RelevanceHLA-B*13:01 is validated as a biomarker for DHS in leprosy patients in Indonesia, and can potentially be a good predictor of DHS to help prevent this condition in the future.KEY POINTSQuestionCan HLA-B*13:01 be a predictor of Dapsone Hypersensitivity Syndrome in Indonesians?FindingsIn this case control validation study, HLA-B*13:01 is significantly associated with DHS in Indonesians and can predict a person at risk of DHS 95% of the time.MeaningHLA-B*13:01 is validated as a biomarker for DHS in Indonesians and can be useful to screen and prevent further incidences of DHS in the population.