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

ALTCHEH, JAIME; ABAL, MANUEL; CRUZ, V; L; BALOUZ,V; GIORGI M. E.; MARINO, C; LEDERKREMER R M; BUSCAGLIA, CA

Chicago

Simposio; 2023 Annual Meeting, American Society of Tropical Medicine and Hygiene; 2023

American Society of Tropical Medicine and Hygiene

Assessment of parasitological cure upon treatment in Chagas Disease (CD) relies on achieving consistent negative results in conventional parasitological and serological tests. Conventional serology (CS) was however optimized for diagnostic purposes and is based on total parasite lysates or mixtures of recombinant Trypanosoma cruzi antigens. Due to their complexity, it may take years or decades for patients to achieve negative seroconversion. Moreover, CS methods display low predictive value for diagnosis and/or follow up of congenital infections due to the passive transfer of maternal antibodies. The F2/3 antigenic fraction, which consists essentially of α-Gal (α-D-Galp(1→3)-β-D-Galp(1→4)-D-GlcNAc) and structurally related α-galactosyl glycotopes from the mucin coat of T. cruzi trypomastigotes is considered one of the gold standards for the serodiagnosis of CD patients. Several methodological drawbacks however preclude its routine implementation in clinical settings. Aiming at developing reliable post-therapeutic biomarkers, we recently developed neoglycoproteins (NPGs) consisting of synthetic α-Gal antigenic surrogates covalently coupled to BSA, which were validated for CD diagnosis. Here we compared the performance of one such NPGs as a biomarker to assess the effectiveness of treatment in pediatric CD. We analyzed 479 samples from 71 follow-ups of T. cruzi-infected and treated children (0-16 years old). In this population α-Gal sensitivity was 53.5% (38/71). In children younger than 1 year (n=15) α-Gal shortened the time of seronegativization as compared to conventional ELISA (TcELISA) (medians of 8 [range 1 to 98] and 33.5 [range 7 to 99] months, respectively). In children from 1 to 7 years old (n=12) the time of α-Gal negativization was also shortened as compared to TcELISA (medians of 48 [range 2 to 107] and 113 [range 46 to 107] months, respectively). Finally, in patients older than 7 years (n=11) the median time of α-Gal negativization was 62 [range 26 to 149] months whereas negativization with TcELISA was not achieved. These results suggest that the α-Gal-containing NPGs shorten follow-up periods, thereby reducing the risks of possible attrition bias and improving the clinical management of pediatric CD. Just as importantly, these reagents provide valuable tools for a better evaluation of new therapeutic drugs, an urgent need in CD.