{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T15:09:52Z","timestamp":1780499392657,"version":"3.54.1"},"reference-count":38,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,3]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    Crimean-Congo hemorrhagic fever (CCHF) is a severe viral infection that may lead to coagulopathy and multiorgan failure. Although the programmed cell death protein 1\/programmed death ligand 1 (PD-L1) immune checkpoint pathway regulates excessive inflammation, the clinical significance of circulating soluble PD-L1 (sPD-L1) in CCHF is not well defined. The aim for the present study was to measure serum sPD-L1 levels in patients with CCHF and evaluate their association with disease severity and prognosis. This prospective study included 60 adults with confirmed CCHF and 30 healthy controls. Disease severity was classified using the Severity Scoring Index. Serum collected on admission was analyzed for sPD-L1, and routine laboratory values were recorded. Clinical and laboratory differences between severity groups were examined, and correlation and receiver operating characteristic analyses were performed. Neurological symptoms, fever, diarrhea, and bleeding were more common in moderate-to-severe cases. These patients had significantly lower platelet and fibrinogen levels and higher alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, international normalized ratio, and activated partial thromboplastin time values. Soluble PD-L1 levels were similar in healthy controls and mild cases but were markedly elevated in moderate-to-severe cases. Soluble PD-L1 accounted for more than half of the variation in severity scores (R\n                    <jats:sup>2<\/jats:sup>\n                    = 0.556). Receiver operating characteristic analysis revealed strong discriminatory ability (area under the curve: 0.901), with a cutoff of 10.91 ng\/mL yielding 96.7% sensitivity and 80% specificity. In conclusion, elevated sPD-L1 levels are closely associated with disease severity in CCHF. Soluble PD-L1 may have prognostic value, although this association should be confirmed in larger studies.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0760","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T18:08:53Z","timestamp":1776794933000},"page":"1184-1190","source":"Crossref","is-referenced-by-count":0,"title":["Association Between Serum Soluble Programmed Death Ligand 1 Levels and Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever"],"prefix":"10.4269","volume":"114","author":[{"given":"Ayten","family":"Yan\u0131k","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Erzurum City Hospital, Erzurum, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00d6mer","family":"Kara\u015fahin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Erzurum City Hospital, Erzurum, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rukiye \u0130nan","family":"Sar\u0131kaya","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Bal\u0131kesir University, Bal\u0131kesir, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rumeysa Temur","family":"\u00c7elik","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Clinical Microbiology, Ataturk University, Erzurum, Turkey;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Engin","family":"\u015eebin","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry, Erzurum City Hospital, Erzurum, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"issue":"5","key":"b1","series-title":"Emerg Infect Dis","first-page":"854","article-title":"Crimean-Congo hemorrhagic fever virus for clinicians\u2014Epidemiology, clinical manifestations, and prevention","volume":"30","author":"Frank","year":"2024"},{"issue":"4","key":"b2","series-title":"Lancet Infect Dis","first-page":"203","article-title":"Crimean-Congo haemorrhagic fever","volume":"6","author":"Erg\u00f6n\u00fcl","year":"2006"},{"issue":"12","key":"b3","series-title":"Clin Chem Lab Med","first-page":"2248","article-title":"Serum sPD-L1 levels are elevated in patients with viral diseases, bacterial sepsis or in patients with impaired renal function compared to healthy blood donors","volume":"61","author":"Loacker","year":"2023"},{"issue":"21","key":"b4","series-title":"J Clin Med","first-page":"6812","article-title":"Different prognostic role of soluble PD-L1 in the course of severe and non-severe COVID-19","volume":"12","author":"Sabbatino","year":"2023"},{"issue":"12","key":"b5","series-title":"Cancers (Basel)","first-page":"3034","article-title":"Soluble programmed death ligand-1 (sPD-L1): A pool of circulating proteins implicated in health and diseases","volume":"13","author":"Bailly","year":"2021"},{"issue":"3","key":"b6","series-title":"Curr Opin Immunol","first-page":"397","article-title":"Role of PD-1 in regulating acute infections","volume":"22","author":"Brown","year":"2010"},{"issue":"5","key":"b7","series-title":"Immunol Res","first-page":"698","article-title":"Soluble PD-L1 in blood correlates positively with neutrophil and negatively with lymphocyte mRNA markers and implies adverse sepsis outcome","volume":"70","author":"Derigs","year":"2022"},{"issue":"1","key":"b8","series-title":"Scand J Immunol","first-page":"e13049","article-title":"Serum-soluble PD-L1 may be a potential diagnostic biomarker in sepsis","volume":"94","author":"Sun","year":"2021"},{"issue":"9","key":"b9","series-title":"Clin Infect Dis","first-page":"1270","article-title":"Severity scoring index for Crimean-Congo hemorrhagic fever and the impact of ribavirin and corticosteroids on fatality","volume":"57","author":"Dokuzoguz","year":"2013"},{"issue":"4","key":"b10","series-title":"J Clin Microbiol","first-page":"e01580-19","article-title":"Diagnostic testing for Crimean-Congo hemorrhagic fever","volume":"58","author":"Raabe","year":"2020"},{"key":"b11","series-title":"Annu Rev Immunol","first-page":"677","article-title":"PD-1 and its ligands in tolerance and immunity","volume":"26","author":"Keir","year":"2008"},{"issue":"1","key":"b12","series-title":"Signal Transduct Target Ther","first-page":"192","article-title":"Storm of soluble immune checkpoints associated with disease severity of COVID-19","volume":"5","author":"Kong","year":"2020"},{"issue":"23","key":"b13","series-title":"Int J Mol Sci","first-page":"12612","article-title":"The role of PD-1\/PD-L1 and IL-7 in lymphocyte dynamics and sepsis progression: A biomarker study in critically ill patients","volume":"25","author":"Coman","year":"2024"},{"issue":"6","key":"b14","series-title":"mBio","first-page":"e01823-23","article-title":"Extracellular vesicles recovered from plasma of severe dengue patients induce CD4+ T cell suppression through PD-L1\/PD-1 interaction","volume":"14","author":"Kumari","year":"2023"},{"issue":"2","key":"b15","series-title":"Cureus","first-page":"e34882","article-title":"The relationship between cytokine concentrations and severity scoring index for Crimean-Congo hemorrhagic fever","volume":"15","author":"Onuk","year":"2023"},{"issue":"4","key":"b16","series-title":"J Clin Virol","first-page":"272","article-title":"Cytokine levels in Crimean-Congo hemorrhagic fever","volume":"36","author":"Papa","year":"2006"},{"issue":"7","key":"b17","series-title":"J Clin Invest","first-page":"2508","article-title":"PD-L1 has distinct functions in hematopoietic and nonhematopoietic cells in regulating T cell responses during chronic infection in mice","volume":"120","author":"Mueller","year":"2010"},{"key":"b18","series-title":"Front Immunol","first-page":"1323797","article-title":"The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways","volume":"14","author":"Chen","year":"2023"},{"issue":"5","key":"b19","series-title":"Crit Care Med","first-page":"1670","article-title":"Serum lactate is associated with mortality in severe sepsis independent of organ failure and shock","volume":"37","author":"Mikkelsen","year":"2009"},{"issue":"5","key":"b1","series-title":"Emerg Infect Dis","first-page":"854","article-title":"Crimean-Congo hemorrhagic fever virus for clinicians\u2014Epidemiology, clinical manifestations, and prevention","volume":"30","author":"Frank","year":"2024"},{"issue":"4","key":"b2","series-title":"Lancet Infect Dis","first-page":"203","article-title":"Crimean-Congo haemorrhagic 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