Laure Gineau1, David Courtin1, Mamadou Camara2, Hamidou Ilboudo3, Vincent Jamonneau4, Fabricio C Dias5, Leonidas Tokplonou6, Jacqueline Milet1, Priscila B Mendonça5, Erick C Castelli7, Oumou Camara2, Mariam Camara2, Benoit Favier8, Nathalie Rouas-Freiss8, Philippe Moreau8, Eduardo A Donadi5, Bruno Bucheton9, Audrey Sabbagh1, André Garcia10. 1. Institut de Recherche pour le Développement, UMR216 MERIT, Mère et Enfant face aux Infections Tropicales Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité. 2. Ministère de la Santé et de l'Hygiène Publique, Programme National de Lutte contre la Trypanosomose Humaine Africaine, Conakry, Guinea. 3. 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. 4. 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. 5. Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto. 6. 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. 7. Department de Pathology, School of Medicine, UNESP-Universidade Estadual Paulista, Botucatu, São Paulo, Brazil. 8. 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. 9. 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. 10. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: Plasma sHLA-G levels were significantly higher in HAT (P = 6 × 10-7) and SERO/HAT (P = .007) than SEROpatients. 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. CONCLUSIONS: These results strongly suggest the involvement of HLA-G in HAT disease progression. Importantly, high plasma sHLA-G levels in SEROpatients 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: Philippe Büscher; Jean-Mathieu Bart; Marleen Boelaert; Bruno Bucheton; Giuliano Cecchi; Nakul Chitnis; David Courtin; Luisa M Figueiredo; José-Ramon Franco; Pascal Grébaut; Epco Hasker; Hamidou Ilboudo; Vincent Jamonneau; Mathurin Koffi; Veerle Lejon; Annette MacLeod; Justin Masumu; Enock Matovu; Raffaele Mattioli; Harry Noyes; Albert Picado; Kat S Rock; Brice Rotureau; Gustave Simo; Sophie Thévenon; Sandra Trindade; Philippe Truc; Nick Van Reet Journal: Trends Parasitol Date: 2018-01-23
Authors: Fabrício C Dias; Bruna C Bertol; Isabelle Poras; Bruno M Souto; Celso T Mendes-Junior; Erick C Castelli; Laure Gineau; Audrey Sabbagh; Nathalie Rouas-Freiss; Edgardo D Carosella; Eduardo A Donadi; Philippe Moreau Journal: Sci Rep Date: 2018-04-04 Impact factor: 4.379