{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T20:02:42Z","timestamp":1767211362837,"version":"3.34.0"},"reference-count":21,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T00:00:00Z","timestamp":1738108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016988","name":"Biomedical Research Institute, Jeonbuk National University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016988","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002701","name":"Ministry of Education","doi-asserted-by":"publisher","award":["NRF-2018R1D1A3B07049557"],"award-info":[{"award-number":["NRF-2018R1D1A3B07049557"]}],"id":[{"id":"10.13039\/501100002701","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec017\">\n<jats:title>Background<\/jats:title>\n<jats:p>Scrub typhus, a disease caused by <jats:italic>Orientia tsutsugamushi<\/jats:italic>, triggers systemic vasculitis and is prevalent in Eastern and Southern Asia. This study aimed to uncover the relationship between scrub typhus and autoimmune responses, focusing on antinuclear antibodies (ANAs) and the implications of elevated ANA titers during infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec018\">\n<jats:title>Method<\/jats:title>\n<jats:p>Data from a total of 139 patients diagnosed with scrub typhus and 30 healthy controls were retrospectively analyzed through serum samples to assess the levels of ANAs and related autoantibodies. The study further examined the temporal variation of these antibody titers in relation to post-symptom progression and evaluated their association with clinical and laboratory parameters.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec019\">\n<jats:title>Results<\/jats:title>\n<jats:p>The study results detail significant differences in autoimmune responses between scrub typhus patients and healthy controls. ANA titers above 1:80 were detected in 71.2% of patients; these titers were elevated in only 13.3% of the healthy controls. High-titer positivity (1:640 or higher) was observed exclusively in the scrub typhus group. The distribution of ANA titers revealed a progressive increase in mean ANA and double-stranded deoxyribonucleic acid Immunoglobulin M (anti-dsDNA IgM) titers as the duration after symptom onset increased, indicating an augmented immune response over time. This trend was observed along with a systematic elevation in median anti-dsDNA IgM titers, highlighting the dynamic nature of immune responses in scrub typhus infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec020\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>Our findings conclude a substantial autoimmunological reaction in scrub typhus patients, suggesting potential mimicry of autoimmune conditions like Systemic Lupus Erythematosus. These results underline the complex interplay between infectious diseases and autoimmunity, emphasizing the necessity for further research into these mechanisms and their clinical implications.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012766","type":"journal-article","created":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T18:32:55Z","timestamp":1738175575000},"page":"e0012766","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["Scrub typhus association with autoimmune biomarkers and clinical implications"],"prefix":"10.1371","volume":"19","author":[{"given":"Hwanseung","family":"You","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeongeun","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seonglyeong","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang-Min","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joo-Hee","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeong-Hwan","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wan-Hee","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7922-0705","authenticated-orcid":true,"given":"Yunjung","family":"Choi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2897-2202","authenticated-orcid":true,"given":"Chang-Seop","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,29]]},"reference":[{"issue":"3","key":"pntd.0012766.ref001","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1099\/00207713-45-3-589","article-title":"Classification of Rickettsia tsutsugamushi in a new genus, Orientia gen. nov., as Orientia tsutsugamushi comb. nov","volume":"45","author":"A Tamura","year":"1995","journal-title":"Int J Syst Bacteriol"},{"key":"pntd.0012766.ref002","doi-asserted-by":"crossref","first-page":"S203","DOI":"10.1086\/596576","article-title":"Scrub typhus: the geographic distribution of phenotypic and genotypic variants of Orientia tsutsugamushi","author":"DJ Kelly","year":"2009","journal-title":"Clin Infect Dis"},{"issue":"10","key":"pntd.0012766.ref003","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1056\/NEJMoa1603657","article-title":"Endemic scrub typhus in South America","volume":"375","author":"T Weitzel","year":"2016","journal-title":"N Engl J Med"},{"key":"pntd.0012766.ref004","doi-asserted-by":"crossref","first-page":"20737","DOI":"10.1038\/srep20737","article-title":"Determination of scrub typhus suggests a new epidemic focus in the Anhui Province of China","volume":"6","author":"M Cao","year":"2016","journal-title":"Sci Rep"},{"issue":"11","key":"pntd.0012766.ref005","doi-asserted-by":"crossref","first-page":"e0006062","DOI":"10.1371\/journal.pntd.0006062","article-title":"A review of the global epidemiology of scrub typhus","volume":"11","author":"G Xu","year":"2017","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012766.ref006","article-title":"Biochemistry, antinuclear antibodies (ANA).","volume-title":"StatPearls","author":"RS Nosal","year":"2024"},{"issue":"10","key":"pntd.0012766.ref007","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/s41584-020-0480-7","article-title":"New insights into the role of antinuclear antibodies in systemic lupus erythematosus","volume":"16","author":"DS Pisetsky","year":"2020","journal-title":"Nat Rev Rheumatol"},{"issue":"1","key":"pntd.0012766.ref008","doi-asserted-by":"crossref","first-page":"52","DOI":"10.4103\/0972-9062.234627","article-title":"Antinuclear antibodies in scrub typhus: transient occurrence during acute illness","volume":"55","author":"M Koshy","year":"2018","journal-title":"J Vector Borne Dis"},{"issue":"2","key":"pntd.0012766.ref009","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4269\/ajtmh.21-0850","article-title":"New genotypes and diversity of Orientia tsutsugamushi DNA samples from patients with scrub typhus in South Korea as determined by multilocus sequence typing","volume":"107","author":"J-H Hwang","year":"2022","journal-title":"Am J Trop Med Hyg"},{"issue":"1","key":"pntd.0012766.ref010","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1097\/00003246-199301000-00019","article-title":"Neurologic complications of critical medical illnesses","volume":"21","author":"TP Bleck","year":"1993","journal-title":"Crit Care Med"},{"issue":"2","key":"pntd.0012766.ref011","doi-asserted-by":"crossref","first-page":"250","DOI":"10.4269\/ajtmh.2011.09-0601","article-title":"Phylogenetic analysis of the 56\u2009kDa protein genes of Orientia tsutsugamushi in Southwest Area of Korea","volume":"84","author":"Y-M Lee","year":"2011","journal-title":"Am J Trop Med Hyg"},{"issue":"7","key":"pntd.0012766.ref012","doi-asserted-by":"crossref","first-page":"e752","DOI":"10.1371\/journal.pntd.0000752","article-title":"High rates of homologous recombination in the mite endosymbiont and opportunistic human pathogen Orientia tsutsugamushi","volume":"4","author":"P Sonthayanon","year":"2010","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0012766.ref013","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.meegid.2010.08.015","article-title":"Diversity of Orientia tsutsugamushi clinical isolates in Cambodia reveals active selection and recombination process","volume":"15","author":"V Duong","year":"2013","journal-title":"Infect Genet Evol"},{"issue":"9","key":"pntd.0012766.ref014","doi-asserted-by":"crossref","first-page":"1400","DOI":"10.1002\/art.40930","article-title":"2019 European league against rheumatism\/American College of rheumatology classification criteria for systemic lupus erythematosus","volume":"71","author":"M Aringer","year":"2019","journal-title":"Arthritis Rheumatol"},{"key":"pntd.0012766.ref015","volume-title":"Kelley and Firestein\u2019s textbook of rheumatology","author":"GS Firestein","year":"2017"},{"issue":"4","key":"pntd.0012766.ref016","doi-asserted-by":"crossref","first-page":"932","DOI":"10.3904\/kjim.2017.224","article-title":"The evaluation of cellular immune function in elderly patients with systemic lupus erythematosus","volume":"34","author":"K Men","year":"2019","journal-title":"Korean J Intern Med"},{"issue":"8","key":"pntd.0012766.ref017","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.it.2009.05.005","article-title":"Infections and autoimmunity \u2013 friends or foes?","volume":"30","author":"S Kivity","year":"2009","journal-title":"Trends Immunol"},{"issue":"6","key":"pntd.0012766.ref018","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1172\/JCI78088","article-title":"Mechanisms of human autoimmunity","volume":"125","author":"MD Rosenblum","year":"2015","journal-title":"J Clin Invest"},{"issue":"4","key":"pntd.0012766.ref019","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1097\/BOR.0000000000000068","article-title":"Infectious triggers for vasculitis","volume":"26","author":"MM Van Timmeren","year":"2014","journal-title":"Curr Opin Rheumatol"},{"key":"pntd.0012766.ref020","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1038\/nri.2016.91","article-title":"Infection stimulates self-antigen presentation","author":"E Kugelberg","year":"2016","journal-title":"Nat Rev Immunol"},{"issue":"2","key":"pntd.0012766.ref021","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1177\/0003319716654079","article-title":"Albumin is an acute or chronic inflammatory marker for in-stent restenosis in patients with coronary artery disease","volume":"68","author":"AG Ertem","year":"2017","journal-title":"Angiology"}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012766","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,29]],"date-time":"2025-01-29T18:33:09Z","timestamp":1738175589000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0012766"}},"subtitle":[],"editor":[{"given":"Yong","family":"Qi","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,29]]},"references-count":21,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,29]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0012766","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,29]]}}}