02462nas a2200301 4500000000100000008004100001260001200042653001400054100001700068700001400085700001500099700001200114700001300126700001800139700001400157700001400171700001000185700001000195700001200205700001500217700001000232245012200242856009900364300001300463490000700476520166300483022001402146 2020 d c10/202010aBiomarker1 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 Indonesia. uhttps://journals.plos.org/plosntds/article/file?id=10.1371/journal.pntd.0008746&type=printable ae00087460 v143 a

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.

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