title: Osteopontin Is Upregulated in Human and Murine Acute Schistosomiasis Mansoni.
abstract: BACKGROUND
  Symptomatic acute schistosomiasis mansoni is a systemic hypersensitivity reaction against the migrating schistosomula and mature eggs after a primary infection. The mechanisms involved in the pathogenesis of acute schistosomiasis are not fully elucidated. Osteopontin has been implicated in granulomatous reactions and in acute hepatic injury. Our aims were to evaluate if osteopontin plays a role in acute Schistosoma mansoni infection in both human and experimentally infected mice and if circulating OPN levels could be a novel biomarker of this infection.
  
  
  RESULTS
  Serum/plasma osteopontin levels were measured by ELISA in patients with acute (n = 28), hepatointestinal (n = 26), hepatosplenic (n = 39) schistosomiasis and in uninfected controls (n = 21). Liver osteopontin was assessed by immunohistochemistry in needle biopsies of 5 patients. Sera and hepatic osteopontin were quantified in the murine model of schistosomiasis mansoni during acute (7 and 8 weeks post infection, n = 10) and chronic (30 weeks post infection, n = 8) phase. Circulating osteopontin levels are increased in patients with acute schistosomiasis (p = 0.0001). The highest levels of OPN were observed during the peak of clinical symptoms (7-11 weeks post infection), returning to baseline level once the granulomas were modulated (>12 weeks post infection). The plasma levels in acute schistosomiasis were even higher than in hepatosplenic patients. The murine model mirrored the human disease. Macrophages were the major source of OPN in human and murine acute schistosomiasis, while the ductular reaction maintains OPN production in hepatosplenic disease. Soluble egg antigens from S. mansoni induced OPN expression in primary human kupffer cells.
  
  
  CONCLUSIONS
  S. mansoni egg antigens induce the production of OPN by macrophages in the necrotic-exudative granulomas characteristic of acute schistosomiasis mansoni. Circulating OPN levels are upregulated in human and murine acute schistosomiasis and could be a non-invasive biomarker of this form of disease.
authors.affiliation: Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, United States of America.|Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.|Laboratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.|Immunopathogesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda,MD, United States of America.
authors.forename: Thiago Almeida
authors.initials: TA
authors.lastname: Pereira
authors.affiliation: Section of Gastroenterology, Ralph H Johnson Veteran Affairs Medical Center, Charleston, South Carolina, United States of America.|Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, United States of America.|Liver Regeneration and Repair Research Group, Institute of Hepatology, Foundation for Liver Research, London, United Kingdom.
authors.forename: Wing-Kin
authors.initials: WK
authors.lastname: Syn
authors.affiliation: Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Frederico Figueiredo
authors.initials: FF
authors.lastname: Amâncio
authors.affiliation: Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Pedro Henrique Diniz
authors.initials: PH
authors.lastname: Cunha
authors.affiliation: Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Julia Fonseca Morais
authors.initials: JF
authors.lastname: Caporali
authors.affiliation: Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.|Department of Physiology, School of Medicine, National University of Ireland, Galway, Ireland.
authors.forename: Guilherme Vaz de Melo
authors.initials: GV
authors.lastname: Trindade
authors.affiliation: Laboratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
authors.forename: Elisângela Trindade
authors.initials: ET
authors.lastname: Santos
authors.affiliation: Laboratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
authors.forename: Márcia Maria
authors.initials: MM
authors.lastname: Souza
authors.affiliation: Laboratório de Patologia Experimental, Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, Salvador, BA, Brazil.
authors.forename: Zilton Araújo
authors.initials: ZA
authors.lastname: Andrade
authors.affiliation: Thermo Fisher Scientific, Frederick, MD, United States of America.
authors.forename: Rafal P
authors.initials: RP
authors.lastname: Witek
authors.affiliation: Centers for Disease Control and Prevention, Atlanta, GA, United States of America.
authors.forename: William Evan
authors.initials: WE
authors.lastname: Secor
authors.affiliation: Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, ES, Brazil.
authors.forename: Fausto Edmundo Lima
authors.initials: FE
authors.lastname: Pereira
authors.affiliation: Departamento de Clínica Médica, Laboratório de Doenças Infecciosas e Parasitárias, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: José Roberto
authors.initials: JR
authors.lastname: Lambertucci
authors.affiliation: Division of Gastroenterology, Department of Medicine, Duke University Medical Center, Durham, NC, United States of America.
authors.forename: Anna Mae
authors.initials: AM
authors.lastname: Diehl
mesh_terms: D000328:Adult; D000818:Animals; D021461:Animals, Outbred Strains; D005260:Female; D006801:Humans; D008099:Liver / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D012550:Schistosoma mansoni / Q000502:physiology*; D012555:Schistosomiasis mansoni / Q000235:genetics* / Q000378:metabolism / Q000469:parasitology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D053495:Osteopontin