{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T15:11:16Z","timestamp":1781709076516,"version":"3.54.5"},"reference-count":20,"publisher":"American Society for Microbiology","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin. Vaccine Immunol."],"published-print":{"date-parts":[[2011,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The objective of this study was to retrospectively evaluate the utility of serum neopterin as a diagnostic marker of hemophagocytic lymphohistiocytosis (HLH). The medical records of patients diagnosed with HLH (familial and secondary) between January 2000 and May 2009 were reviewed retrospectively, and clinical and laboratory information related to HLH criteria, in addition to neopterin levels, was recorded. A group of 50 patients with active juvenile dermatomyositis (JDM) (who routinely have neopterin levels assessed) served as controls for the assessment of the accuracy, sensitivity, and specificity of neopterin as a diagnostic test for HLH. The Pearson correlation was used to measure the association between serum neopterin levels and established HLH-related laboratory data. Serum neopterin levels were measured using a competitive enzyme immunoassay. During the time frame of the study, 3 patients with familial HLH and 18 patients with secondary HLH were identified as having had serum neopterin measured (all HLH patients were grouped together). The mean neopterin levels were 84.9 nmol\/liter (standard deviation [SD], 83.4 nmol\/liter) for patients with HLH and 21.5 nmol\/liter (SD, 10.13 nmol\/liter) for patients with JDM. A cutoff value of 38.9 nmol\/liter was 70% sensitive and 95% specific for HLH. For HLH patients, neopterin levels correlated significantly with ferritin levels (<jats:italic>r<\/jats:italic>= 0.76,<jats:italic>P<\/jats:italic>= 0.0007). In comparison to the level in a control group of JDM patients, elevated serum neopterin was a sensitive and specific marker for HLH. Serum neopterin has value as a diagnostic marker of HLH, and prospective studies are under way to further evaluate its role as a marker for early diagnosis and management of patients.<\/jats:p>","DOI":"10.1128\/cvi.00306-10","type":"journal-article","created":{"date-parts":[[2011,1,27]],"date-time":"2011-01-27T02:44:09Z","timestamp":1296096249000},"page":"609-614","source":"Crossref","is-referenced-by-count":40,"title":["Serum Neopterin Levels as a Diagnostic Marker of Hemophagocytic Lymphohistiocytosis Syndrome"],"prefix":"10.1128","volume":"18","author":[{"given":"Maria F.","family":"Ibarra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Klein-Gitelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Proytcheva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren M.","family":"Pachman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice R. G.","family":"O'Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2011,1,26]]},"reference":[{"key":"key20180919073508_B1","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1002\/pbc.21423","article-title":"Highly elevated ferritin levels and the diagnosis of hemophagocytic lymphohistiocytosis","volume":"50","author":"Allen","year":"2008","journal-title":"Pediatr. Blood Cancer"},{"key":"key20180919073508_B2","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1056\/NEJM197502132920706","article-title":"Polymyositis and dermatomyositis","volume":"292","author":"Bohan","year":"1975","journal-title":"N. Engl. J. Med."},{"key":"key20180919073508_B3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1097\/PCC.0b013e3181a1ae08","article-title":"Secondary hemophagocytic lymphohistiocytosis and severe sepsis\/systemic inflammatory response syndrome\/multiorgan dysfunction syndrome\/macrophage activation syndrome share common intermediate phenotypes on a spectrum of inflammation","volume":"10","author":"Castillo","year":"2009","journal-title":"Pediatr. Crit. Care Med."},{"key":"key20180919073508_B4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1136\/adc.69.2.232","article-title":"Correlation of serum neopterin concentrations with disease activity in juvenile dermatomyositis","volume":"2","author":"De Benedetti","year":"1993","journal-title":"Arch. Dis. Child."},{"key":"key20180919073508_B5","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1182\/blood-2005-11-4413","article-title":"Lethal hemophagocytic lymphohistiocytosis in Hermansky-Pudlak syndrome type II","volume":"108","author":"Enders","year":"2006","journal-title":"Blood"},{"key":"key20180919073508_B6","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1097\/01.all.0000246626.57118.d9","article-title":"Hemophagocytic lymphohistiocytosis and related disorders","volume":"6","author":"Filipovich","year":"2006","journal-title":"Curr. Opin. Allergy Clin. Immunol."},{"issue":"44","key":"key20180919073508_B7","doi-asserted-by":"crossref","first-page":"6840","DOI":"10.3748\/wjg.14.6840","article-title":"Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity","volume":"14","author":"Gulcan","year":"2008","journal-title":"World J. Gastroenterol."},{"issue":"2","key":"key20180919073508_B8","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1002\/pbc.21039","article-title":"HLH-2004: diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007","journal-title":"Pediatr. Blood Cancer"},{"key":"key20180919073508_B9","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1084\/jem.160.1.310","article-title":"Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma","volume":"160","author":"Humber","year":"1984","journal-title":"J. Exp. Med."},{"key":"key20180919073508_B10","doi-asserted-by":"crossref","first-page":"3023","DOI":"10.1002\/cncr.10515","article-title":"Low natural killer activity and central nervous system disease as a high-risk prognostic indicator for young patients with hemophagocytic lymphohistiocytosis (HLH)","volume":"94","author":"Imashuku","year":"2002","journal-title":"Cancer"},{"issue":"10","key":"key20180919073508_B11","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1200\/JCO.2001.19.10.2665","article-title":"Requirement for etoposide in the treatment of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis","volume":"19","author":"Imashuku","year":"2001","journal-title":"J. Clin. Oncol."},{"key":"key20180919073508_B12","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s00431-006-0258-1","article-title":"Familial and acquired hemophagocytic lymphohystiocytosis","volume":"166","author":"Janka","year":"2007","journal-title":"Eur. J. Pediat."},{"key":"key20180919073508_B13","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1097\/BOR.0b013e32825a6a79","article-title":"Recognition and management of macrophage activation syndrome in juvenile arthritis","volume":"19","author":"Kelly","year":"2007","journal-title":"Curr. Opin. Rheumatol."},{"key":"key20180919073508_B14","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1086\/427877","article-title":"Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection","volume":"40","author":"Mildvan","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"key20180919073508_B15","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1080\/10428190802258956","article-title":"Evaluation of procalcitonin, neopterin, C-reactive protein, IL-6 and IL-8 as a diagnostic marker of infection in patients with febrile neutropenia","volume":"49","author":"Prat","year":"2008","journal-title":"Leuk. Lymphoma"},{"key":"key20180919073508_B16","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1136\/adc.85.5.421","article-title":"Macrophage activation syndrome: a potentially fatal complication of rheumatic disorders","volume":"85","author":"Sawhney","year":"2001","journal-title":"Arch. Dis. Child."},{"key":"key20180919073508_B17","doi-asserted-by":"crossref","unstructured":"ShimizuM.. 14 May 2010, posting date. Distinct cytokine profiles of systemic-onset juvenile idiopathic arthritis-associated macrophage activation syndrome with particular emphasis on the role of interleukin-18 in its pathogenesis. Rheumatology. doi: 10.1093\/rheumatology\/keq133.","DOI":"10.1093\/rheumatology\/keq133"},{"key":"key20180919073508_B18","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.canlet.2009.05.008","article-title":"Neopterin, a prognostic marker in human malignancies","volume":"287","author":"Sucher","year":"2010","journal-title":"Cancer Lett."},{"key":"key20180919073508_B19","unstructured":"SumegiJ.\nJohnsonJ.\nFilipovichA.\nZhanK.\nMarshR.. 27 February 2004, posting date. Lymphoproliferative disease, X-linked. GeneReviews. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1406\/."},{"key":"key20180919073508_B20","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/0021-9150(91)90061-7","article-title":"Elevated serum neopterin levels in atherosclerosis","volume":"2-3","author":"Tatzber","year":"1991","journal-title":"Atherosclerosis"}],"container-title":["Clinical and Vaccine Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1128\/CVI.00306-10","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T20:44:50Z","timestamp":1627591490000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/CVI.00306-10"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,26]]},"references-count":20,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2011,4,6]]},"published-print":{"date-parts":[[2011,4]]}},"alternative-id":["10.1128\/CVI.00306-10"],"URL":"https:\/\/doi.org\/10.1128\/cvi.00306-10","relation":{},"ISSN":["1556-6811","1556-679X"],"issn-type":[{"value":"1556-6811","type":"print"},{"value":"1556-679X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,26]]}}}