USEFULNESS OF ANTI Α-GAL ANTIBODIES AS BIOMARKERS OF THERAPEUTIC RESPONSE IN CHAGAS DISEASE

ALTCHEH, JAIME; ABAL, MANUEL; CRUZ, CINTIA V; BALOUZ, VIRGINIA; GIORGI, M. EUGENIA; MARINO, CARLA; DE LEDERKREMER, ROSA M.; BUSCAGLIA, CARLOS A.

Chicago

Encuentro; ASTMH-2023 Annual Meeting; 2023

American Society of Tropical Medicine and Hygiene

Assessment of parasitological cure in Chagas Disease (CD) relies on achieving consistent negative results in parasitological and conventional serological tests. However, conventional serological reagents were optimized for diagnosis. These are based on mixtures of native or recombinant Trypanosoma cruzi antigens and display suboptimal performance as post-therapeutic biomarkers with low specificity and a long period required for negativization after treatment (known as seroconversion). Novel biomarkers are urgently needed. The F2/3 antigenic fraction of T. cruzi tripomastigotes, whose major epitope is the α-Gal glycan (Galp(α1-3) Galp(β1-4) GlcNAc), has been proposed as biomarker of early treatment response. However, its standardization remains challenging as large quantities of live infective parasites are required to produce it. We recently developed a synthetic αGal antigen. Here, we evaluated the use of antibodies anti αGal antigen as a biomarkers of treatment efficacy in a cohort of T. cruzi-infected children. Serological responses against αGal antigen were evaluated using an in-house enzymelinked immunosorbent assay (ELISA) and compared to conventional ELISA (TcELISA). We included 71 children (0-16 years old) with 479 samples in total. At baseline, αGal antibody was reactive in 38/71 patients (53.5%). After treatment, in children < 1 year (n=15) αGal antibodies became negative earlier than TcELISA (median of 8 months [range 1 to 98] and 33.5 mo [range 7 to 99], respectively). In children 1 to 7 years old (n=12) the seroconversion was also earlier than with TcELISA (median of 48 months [range 2 to 107] and 113 months [range 46 to 107], respectively). Finally, in patients older than 7 years (n=11) the median time of negativization with αGal was 62 months [range 26 to 149] whereas TcELISA did not became negative. This is the first study that evaluates the performance of αGal as biomarker of treatment response in CD. Our results suggest that the antibodies anti αGal would shorten follow-up periods following CD treatment. Just as important, αGal would facilitate the implementation of clinical trials with new drugs, an urgent need in CD.