02872nas a2200241 4500000000100000008004100001260003400042100001700076700001400093700001500107700001200122700001300134700001800147700001400165700001400179700001000193700001000203700001200213700001500225700001000240245012100250520225900371 d bCold Spring Harbor Laboratory1 aKrismawati H1 aIrwanto A1 aPongtiku A1 aIrwan I1 aMaldan Y1 aSitanggang YA1 aWahyuni T1 aTanjung R1 aSun Y1 aLiu H1 aZhang F1 aOktavian A1 aLiu J00aValidation Study of HLA-B*13:01 as a Biomarker of Dapsone Hypersensitivity Syndrome in Leprosy Patients in Indonesia3 aImportance: Leprosy 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. Objective: To validate HLA-B*13:01 as a biomarker for DHS in the Indonesian population. Design: This is a case-control study. Setting: Population-based, multi-district recruitment from primary care centers in two of the top 3 most prevalent provinces in Indonesia, Papua and West Papua. Participants: Leprosy 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). Exposure: Leprosy patients who had undergone multi-drug treatment for leprosy under the standard WHO guideline, consisting of rifampicin, dapsone and clofazamine. Main Outcome and Measures: The 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. Results: The 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 Relevance: HLA-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. Keywords: HLA-B*13:01, dapsone hypersensitivity syndrome, leprosy, dapsone, adverse drug reaction, Papua, Indonesia