Lymphotoxin alpha gene polymorphism influences the cardiomyopathy development in chagas’ disease patients (88.16)

Abstract

Chagas’ disease, caused by Trypanosoma cruzi, is an important parasitic disease in Latin America, affecting more than 8 millions of people. The chronic phase is characterized by commitment of heart or digestive organs and the reason for the development of one clinical form or another is not well known. It is speculated that host and parasite genetic characteristics contribute for it. LT-α is an inflammatory cytokine, important in the organization and maintenance of the inflammatory process by stimulating adhesion molecules, such as VCAM, ICAM and E-selectin. Polymorphism on LT-α gene, position +252, were analyzed on subjects (n= 295) from an endemic area for Chagas’ disease grouped according to serology for T. cruzi and with clinical form (cardiac or indeterminate forms).Expression of LT-α was evaluated in culture supernatants and by flow cytometry. Presence of G allele was significantly more frequent in patients with heart commitment (cardiac form) (p=0.016, OR=2.4). Patients with cardiac form produced significantly more LT-α than individuals with the indeterminate form. Furthermore, infected individuals with G allele produced significantly higher levels of LT-α than those without G allele. CD8+ T lymphocytes were the major source of LT-α in basal condition and after stimulation with specific antigens. This study presents genetic and biological evidence for a role of LT-α in the development of cardiac form of Chagas’ disease.