TY - JOUR
T1 - Validation study of hla-b* 13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia
AU - Krismawati, Hana
AU - Irwanto, Astrid
AU - Pongtiku, Arry
AU - Irwan, Ishak Darryl
AU - Maladan, Yustinus
AU - Sitanggang, Yuli Arisanti
AU - Wahyuni, Tri
AU - Tanjung, Ratna
AU - Sun, Yonghu
AU - Liu, Hong
AU - Zhang, Furen
AU - Oktavian, Antonius
AU - Liu, Jianjun
N1 - Funding Information:
Funding:ThisworkwassupportedbyNational InstituteofHealthResearchandDevelopment, MinistryofHealthRepublicofIndonesia(Grant no:2069.053.051B,forauthorsHK,YM,YAS,TW, RT,AO),GenomeInstituteofSingapore,Agency forScienceTechnologyandResearch(Core FundingandGrantno:ETPL/17-GAP016-R20H,for authorsAI,JL),NationalKeyResearchand DevelopmentProgramofChina(Grantno: 2016YFE0201500,forauthorsYS,HL,FZ).The fundershadnoroleinstudydesign,datacollection andanalysis,decisiontopublish,orpreparationof themanuscript.
Publisher Copyright:
© 2020 Krismawati et al.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/10
Y1 - 2020/10
N2 - 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 ana-lysed using logistic regression and risk assessment was carried out. The results of HLA-typ-ing 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 bio-marker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good pre-dictor of DHS to help prevent this condition in the future.
AB - 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 ana-lysed using logistic regression and risk assessment was carried out. The results of HLA-typ-ing 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 bio-marker for DHS in leprosy patients in Papua, Indonesia, and can potentially be a good pre-dictor of DHS to help prevent this condition in the future.
UR - http://www.scopus.com/inward/record.url?scp=85094932391&partnerID=8YFLogxK
U2 - 10.1371/journal.pntd.0008746
DO - 10.1371/journal.pntd.0008746
M3 - Article
C2 - 33064728
AN - SCOPUS:85094932391
SN - 1935-2727
VL - 14
SP - 1
EP - 11
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 10
M1 - e0008746
ER -
