Validation study of HLA-B13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia
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 proble...
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| creator | Krismawati, Hana Irwanto, Astrid Pongtiku, Arry Irwan, Ishak Darryl Maladan, Yustinus Sitanggang, Yuli Arisanti Wahyuni, Tri Tanjung, Ratna Sun, Yonghu Liu, Hong Zhang, Furen Oktavian, Antonius Liu, Jianjun |
| description | 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. |
| doi_str_mv | 10.1371/journal.pntd.0008746 |
| format | Article |
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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.</description><identifier>ISSN: 1935-2735</identifier><identifier>ISSN: 1935-2727</identifier><identifier>EISSN: 1935-2735</identifier><identifier>DOI: 10.1371/journal.pntd.0008746</identifier><identifier>PMID: 33064728</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject><![CDATA[Adolescent ; Adult ; Alleles ; Antibiotics ; Biological markers ; Biology and Life Sciences ; Biomarkers ; Case-Control Studies ; Chemotherapy ; Chronic infection ; Clofazimine ; Clofazimine - administration & dosage ; Complications and side effects ; Consent ; Dapsone ; Dapsone - administration & dosage ; Dapsone - adverse effects ; Deoxyribonucleic acid ; Dermatology ; Diagnosis ; Diaminodiphenylsulfone ; DNA ; Drug allergy ; Drug Hypersensitivity - epidemiology ; Drug Hypersensitivity - prevention & control ; Drug therapy ; Drug Therapy, Combination ; Female ; Funding ; Genomes ; Health aspects ; Histocompatibility antigen HLA ; Histocompatibility antigens ; HIV ; HLA histocompatibility antigens ; HLA-B13 Antigen - genetics ; Hospitals ; Human immunodeficiency virus ; Humans ; Hypersensitivity ; Indonesia ; Leprostatic Agents - administration & dosage ; Leprostatic Agents - adverse effects ; Leprosy ; Leprosy - drug therapy ; Logistic Models ; Male ; Medical research ; Medicine and Health Sciences ; Mortality ; Nervous system ; Nucleotide sequence ; Patients ; People and places ; Pneumonia ; R&D ; Regression analysis ; Research & development ; Rifampin ; Rifampin - administration & dosage ; Risk Assessment ; Risk factors ; Skin diseases ; Specificity ; Syndrome ; Therapy ; Tissue typing ; Tropical diseases ; Young Adult]]></subject><ispartof>PLoS neglected tropical diseases, 2020-10, Vol.14 (10), p.e0008746</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>2020 Krismawati et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2020 Krismawati et al 2020 Krismawati et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-b50ca79d02a803ed0a7b9fffc7a62fe1df661fd897fb905395b6be36f7be74f93</citedby><cites>FETCH-LOGICAL-c554t-b50ca79d02a803ed0a7b9fffc7a62fe1df661fd897fb905395b6be36f7be74f93</cites><orcidid>0000-0003-3190-3109 ; 0000-0002-3255-3019</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592909/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592909/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33064728$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Krismawati, Hana</creatorcontrib><creatorcontrib>Irwanto, Astrid</creatorcontrib><creatorcontrib>Pongtiku, Arry</creatorcontrib><creatorcontrib>Irwan, Ishak Darryl</creatorcontrib><creatorcontrib>Maladan, Yustinus</creatorcontrib><creatorcontrib>Sitanggang, Yuli Arisanti</creatorcontrib><creatorcontrib>Wahyuni, Tri</creatorcontrib><creatorcontrib>Tanjung, Ratna</creatorcontrib><creatorcontrib>Sun, Yonghu</creatorcontrib><creatorcontrib>Liu, Hong</creatorcontrib><creatorcontrib>Zhang, Furen</creatorcontrib><creatorcontrib>Oktavian, Antonius</creatorcontrib><creatorcontrib>Liu, Jianjun</creatorcontrib><title>Validation study of HLA-B13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia</title><title>PLoS neglected tropical diseases</title><addtitle>PLoS Negl Trop Dis</addtitle><description>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.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Alleles</subject><subject>Antibiotics</subject><subject>Biological markers</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers</subject><subject>Case-Control Studies</subject><subject>Chemotherapy</subject><subject>Chronic infection</subject><subject>Clofazimine</subject><subject>Clofazimine - administration & dosage</subject><subject>Complications and side effects</subject><subject>Consent</subject><subject>Dapsone</subject><subject>Dapsone - administration & dosage</subject><subject>Dapsone - adverse effects</subject><subject>Deoxyribonucleic acid</subject><subject>Dermatology</subject><subject>Diagnosis</subject><subject>Diaminodiphenylsulfone</subject><subject>DNA</subject><subject>Drug allergy</subject><subject>Drug Hypersensitivity - epidemiology</subject><subject>Drug Hypersensitivity - prevention & control</subject><subject>Drug therapy</subject><subject>Drug Therapy, Combination</subject><subject>Female</subject><subject>Funding</subject><subject>Genomes</subject><subject>Health aspects</subject><subject>Histocompatibility antigen HLA</subject><subject>Histocompatibility antigens</subject><subject>HIV</subject><subject>HLA histocompatibility antigens</subject><subject>HLA-B13 Antigen - genetics</subject><subject>Hospitals</subject><subject>Human immunodeficiency virus</subject><subject>Humans</subject><subject>Hypersensitivity</subject><subject>Indonesia</subject><subject>Leprostatic Agents - administration & dosage</subject><subject>Leprostatic Agents - adverse effects</subject><subject>Leprosy</subject><subject>Leprosy - drug therapy</subject><subject>Logistic Models</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine and Health Sciences</subject><subject>Mortality</subject><subject>Nervous system</subject><subject>Nucleotide sequence</subject><subject>Patients</subject><subject>People and places</subject><subject>Pneumonia</subject><subject>R&D</subject><subject>Regression analysis</subject><subject>Research & development</subject><subject>Rifampin</subject><subject>Rifampin - administration & dosage</subject><subject>Risk Assessment</subject><subject>Risk factors</subject><subject>Skin diseases</subject><subject>Specificity</subject><subject>Syndrome</subject><subject>Therapy</subject><subject>Tissue typing</subject><subject>Tropical diseases</subject><subject>Young 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biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia</atitle><jtitle>PLoS neglected tropical diseases</jtitle><addtitle>PLoS Negl Trop Dis</addtitle><date>2020-10-01</date><risdate>2020</risdate><volume>14</volume><issue>10</issue><spage>e0008746</spage><pages>e0008746-</pages><issn>1935-2735</issn><issn>1935-2727</issn><eissn>1935-2735</eissn><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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33064728</pmid><doi>10.1371/journal.pntd.0008746</doi><orcidid>https://orcid.org/0000-0003-3190-3109</orcidid><orcidid>https://orcid.org/0000-0002-3255-3019</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1935-2735 |
| ispartof | PLoS neglected tropical diseases, 2020-10, Vol.14 (10), p.e0008746 |
| issn | 1935-2735 1935-2727 1935-2735 |
| language | eng |
| recordid | cdi_plos_journals_2460997841 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; PubMed Central Open Access; Public Library of Science (PLoS) |
| subjects | Adolescent Adult Alleles Antibiotics Biological markers Biology and Life Sciences Biomarkers Case-Control Studies Chemotherapy Chronic infection Clofazimine Clofazimine - administration & dosage Complications and side effects Consent Dapsone Dapsone - administration & dosage Dapsone - adverse effects Deoxyribonucleic acid Dermatology Diagnosis Diaminodiphenylsulfone DNA Drug allergy Drug Hypersensitivity - epidemiology Drug Hypersensitivity - prevention & control Drug therapy Drug Therapy, Combination Female Funding Genomes Health aspects Histocompatibility antigen HLA Histocompatibility antigens HIV HLA histocompatibility antigens HLA-B13 Antigen - genetics Hospitals Human immunodeficiency virus Humans Hypersensitivity Indonesia Leprostatic Agents - administration & dosage Leprostatic Agents - adverse effects Leprosy Leprosy - drug therapy Logistic Models Male Medical research Medicine and Health Sciences Mortality Nervous system Nucleotide sequence Patients People and places Pneumonia R&D Regression analysis Research & development Rifampin Rifampin - administration & dosage Risk Assessment Risk factors Skin diseases Specificity Syndrome Therapy Tissue typing Tropical diseases Young Adult |
| title | Validation study of HLA-B13:01 as a biomarker of dapsone hypersensitivity syndrome in leprosy patients in Indonesia |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T06%3A28%3A47IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Validation%20study%20of%20HLA-B13:01%20as%20a%20biomarker%20of%20dapsone%20hypersensitivity%20syndrome%20in%20leprosy%20patients%20in%20Indonesia&rft.jtitle=PLoS%20neglected%20tropical%20diseases&rft.au=Krismawati,%20Hana&rft.date=2020-10-01&rft.volume=14&rft.issue=10&rft.spage=e0008746&rft.pages=e0008746-&rft.issn=1935-2735&rft.eissn=1935-2735&rft_id=info:doi/10.1371/journal.pntd.0008746&rft_dat=%3Cgale_plos_%3EA645332932%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2460997841&rft_id=info:pmid/33064728&rft_galeid=A645332932&rft_doaj_id=oai_doaj_org_article_c783291113b74b05aa9da407139ec057&rfr_iscdi=true |