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

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.

• Authors: Laure Gineau, David Courtin, Mamadou Camara, Hamidou Ilboudo, Vincent Jamonneau, Fabricio C Dias, Leonidas Tokplonou, Jacqueline Milet, Priscila B Mendonça, Erick C Castelli, Oumou Camara, Mariam Camara, Benoit Favier, Nathalie Rouas-Freiss, Philippe Moreau, Eduardo A Donadi, Bruno Bucheton, Audrey Sabbagh, André Garcia
• Journal: Clinical infectious diseases : an official publication of the Infectious Diseases Society of America (Clin Infect Dis) Vol. 63 Issue 9 Pg. 1189-1197 (11 01 2016) ISSN: 1537-6591 [Electronic] United States
• PMID: 27470243 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail [email protected].

Chemical References

• Biomarkers
• HLA-G Antigens

Topics

• Adult
• Biomarkers (blood)
• Disease Progression
• Female
• HLA-G Antigens (blood)
• Haplotypes
• Humans
• Male
• Prognosis
• Trypanosoma brucei gambiense
• Trypanosomiasis, African (blood, physiopathology, prevention & control)