Human Leukocyte Antigen-G: A Promising Prognostic Marker of Disease Progression to Improve the Control of Human African Trypanosomiasis

• Autor(a) principal: Gineau, Laure
• Data de Publicação: 2016
• Outros Autores: Courtin, David, Camara, Mamadou, Ilboudo, Hamidou, Jamonneau, Vincent, Dias, Fabricio C., Tokplonou, Leonidas, Milet, Jacqueline, Mendonça, Priscila B., Castelli, Erick C. [UNESP], Camara, Oumou, Camara, Mariam, Favier, Benoit, Rouas-Freiss, Nathalie, Moreau, Philippe, Donadi, Eduardo A., Bucheton, Bruno, Sabbagh, Audrey, Garcia, André
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1093/cid/ciw505; http://hdl.handle.net/11449/176957
• topic: genetic association; HLA-G; human African trypanosomiasis; susceptibility; Trypanosoma brucei gambiense

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.