Autoantibodies against the immunodominant sCha epitope discriminate the risk of sudden death in chronic Chagas cardiomyopathy

Héctor O. Rodríguez-Angulo, Andrés Lamsfus-Calle, Javier Isoler-Alcaráz, Javier Galán-Martínez, Alfonso Herreros-Cabello, Francisco Callejas-Hernández, María A. Chorro-de-Villaceballos, María C. Maza, Julien Santi-Rocca, Cristina Poveda, Javier Del Moral-Salmoral, Juan Marques, Iván Mendoza, Juan David Ramírez, Felipe Guhl, Irene Carrillo, Ramón Pérez-Tanoira, Miguel Górgolas, Ana Pérez-Ayala, Begoña Monge-MailloFrancesca Norman, José A. Pérez-Molina, Rogelio López-Vélez, Manuel Fresno, Núria Gironès

Research output: Contribution to journalArticlepeer-review

Abstract

In Chagas disease (ChD) caused by Trypanosoma cruzi, new biomarkers to predict chronic cardiac pathology are urgently needed. Previous studies in chagasic patients with mild symptomatology showed that antibodies against the immunodominant R3 epitope of sCha, a fragment of the human basic helix-loop-helix transcription factor like 5, correlated with cardiac pathology. To validate sCha as a biomarker and to understand the origin of anti-sCha antibodies, we conducted a multicenter study with several cohorts of chagasic patients with severe cardiac symptomatology. We found that levels of antibodies against sCha discriminated the high risk of sudden death, indicating they could be useful for ChD prognosis. We investigated the origin of the antibodies and performed an alanine scan of the R3 epitope. We identified a minimal epitope MRQLD, and a BLAST search retrieved several T. cruzi antigens. Five of the hits had known or putative functions, of which phosphonopyruvate decarboxylase showed the highest cross-reactivity with sCha, confirming the role of molecular mimicry in the development of anti-sCha antibodies. Altogether, we demonstrate that the development of antibodies against sCha, which originated by molecular mimicry with T. cruzi antigens, could discriminate electrocardiographic alterations associated with a high risk of sudden death.

Original languageEnglish (US)
Pages (from-to)27-38
Number of pages12
JournalAnnals of the New York Academy of Sciences
Volume1497
Issue number1
DOIs
StatePublished - 2021

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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