Autoantibodies against the immunodominant sCha epitope discriminate the risk of sudden death in chronic Chagas cardiomyopathy.
Chagas
Trypanosoma cruzi
alanine scan
cardiomyopathy
immunodominant epitope
prognosis
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
revised:
07
02
2021
received:
14
01
2021
accepted:
12
02
2021
pubmed:
9
3
2021
medline:
15
12
2021
entrez:
8
3
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Antibodies, Protozoan
0
Autoantibodies
0
Biomarkers
0
Immunodominant Epitopes
0
Types de publication
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
27-38Subventions
Organisme : Secretaría de Estado de Investigación, Desarrollo e Innovación
ID : SAF2015-63868-R
Organisme : Secretaría de Estado de Investigación, Desarrollo e Innovación
ID : SAF2016-75988-R
Organisme : Instituto de Salud Carlos III
ID : RD12/0018/0004
Organisme : UAM-Santander
ID : CEAL-AL/2015-12
Organisme : Ministerio de Ciencia e Innovación
ID : PGC2018-096132-B-I00
Organisme : Consejería de Educación e Investigación
ID : S-2010/BMD-2332
Informations de copyright
© 2021 New York Academy of Sciences.
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