title: Human Leukocyte Antigen-G: A Promising Prognostic Marker of Disease Progression to Improve the Control of Human African Trypanosomiasis.
abstract: Human African trypanosomiasis (HAT) caused by Trypanosoma brucei gambiense can be diagnosed in the early hemolymphatic stage (stage 1 [S1]) or meningoencephalitic stage (stage 2 [S2]). Importantly, individuals harbouring high and specific antibody responses to Tbg antigens but negative parasitology are also diagnosed in the field (seropositive [SERO]). Whereas some develop the disease in the months following their initial diagnosis (SERO/HAT), others remain parasitologically negative for long periods (SERO) and are apparently able to control infection. Human leucocyte antigen (HLA)-G, an immunosuppressive molecule, could play a critical role in this variability of progression between infection and disease.
  
  
  
  Soluble HLA-G (sHLA-G) was measured in plasma for patients in the SERO (n = 65), SERO/HAT (n = 14), or HAT (n = 268) group and in cerebrospinal fluid for patients in S1 (n = 55), early S2 (n = 93), or late S2 (n = 110). Associations between these different statuses and the soluble level or genetic polymorphisms of HLA-G were explored.
  
  
  
  Plasma sHLA-G levels were significantly higher in HAT (P = 6 × 10-7) and SERO/HAT (P = .007) than SERO patients. No difference was observed between the SERO/HAT and HAT groups. Within the HAT group, specific haplotypes (HG010102 and HG0103) displayed increased frequencies in S1 (P = .013) and late S2 (P = .036), respectively.
  
  
  
  These results strongly suggest the involvement of HLA-G in HAT disease progression. Importantly, high plasma sHLA-G levels in SERO patients could be predictive of subsequent disease development and could represent a serological marker to help guide therapeutic decision making. Further studies are necessary to assess the predictive nature of HLA-G and to estimate both sensitivity and specificity.
authors.affiliation: Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité.
authors.forename: Laure
authors.initials: L
authors.lastname: Gineau
authors.affiliation: Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité.
authors.forename: David
authors.initials: D
authors.lastname: Courtin
authors.affiliation: Ministère de la Santé et de l'Hygiène Publique, Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Camara
authors.affiliation: Centre International de Recherche-Développement sur l'Elevage en Zones Subhumides, Unité de Recherches sur les Bases Biologiques de la Lutte Intégrée, Bobo-Dioulasso, Burkina Faso.
authors.forename: Hamidou
authors.initials: H
authors.lastname: Ilboudo
authors.affiliation: Centre International de Recherche-Développement sur l'Elevage en Zones Subhumides, Unité de Recherches sur les Bases Biologiques de la Lutte Intégrée, Bobo-Dioulasso, Burkina Faso Institut de Recherche Pour le Développement, Campus International de Baillarguet, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jamonneau
authors.affiliation: Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto.
authors.forename: Fabricio C
authors.initials: FC
authors.lastname: Dias
authors.affiliation: Institut de Recherche Pour le Développement, UMR 216, Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Cotonou, Bénin.
authors.forename: Leonidas
authors.initials: L
authors.lastname: Tokplonou
authors.affiliation: Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Milet
authors.affiliation: Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto.
authors.forename: Priscila B
authors.initials: PB
authors.lastname: Mendonça
authors.affiliation: Department de Pathology, School of Medicine, UNESP-Universidade Estadual Paulista, Botucatu, São Paulo, Brazil.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.affiliation: Ministère de la Santé et de l'Hygiène Publique, Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea.
authors.forename: Oumou
authors.initials: O
authors.lastname: Camara
authors.affiliation: Ministère de la Santé et de l'Hygiène Publique, Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea.
authors.forename: Mariam
authors.initials: M
authors.lastname: Camara
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis Université Paris Diderot, Sorbonne Paris Cité, UMRE5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis.
authors.forename: Benoit
authors.initials: B
authors.lastname: Favier
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis Université Paris Diderot, Sorbonne Paris Cité, UMRE5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rouas-Freiss
authors.affiliation: Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Thérapies Innovantes, Service de Recherches en Hémato-Immunologie, Hôpital Saint-Louis Université Paris Diderot, Sorbonne Paris Cité, UMRE5, Institut Universitaire d'Hématologie, Hôpital Saint-Louis.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Ministère de la Santé et de l'Hygiène Publique, Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea Institut de Recherche Pour le Développement, Campus International de Baillarguet, Montpellier, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bucheton
authors.affiliation: Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sabbagh
authors.affiliation: Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité Institut de Recherche Pour le Développement, UMR 216, Centre d'Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l'Enfance, Faculté des Sciences de la Santé, Cotonou, Bénin.
authors.forename: André
authors.initials: A
authors.lastname: Garcia
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D059951:HLA-G Antigens / Q000097:blood*; D006239:Haplotypes; D006801:Humans; D008297:Male; D011379:Prognosis; D014347:Trypanosoma brucei gambiense; D014353:Trypanosomiasis, African / Q000097:blood* / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D059951:HLA-G Antigens
keywords: HLA-G; Trypanosoma brucei gambiense; genetic association; human African trypanosomiasis; susceptibility