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Association between the lymphotoxin-alpha gene polymorphism and chagasic cardiopathy

Cristina Wide Pissetti1, Rafael Faria de Oliveira, Dalmo Correia

  • 1Laboratory of Immunology, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil. cristinawpissetti@gmail.com

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|January 8, 2013
PubMed

Insights

Genetic variations in Lymphotoxin-alpha (LT-alpha) increase the risk of developing cardiac Chagas

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Lymphotoxin-alpha (LT-alpha) is a key inflammatory cytokine involved in immune responses and tissue organization.
  • Its role in chronic inflammation suggests a potential link to the pathogenesis of chronic Chagas' disease, particularly cardiac complications.

Purpose of the Study:

  • To investigate the genetic associations of LT-alpha polymorphisms with chronic Chagas' disease.
  • To explore the biological expression and function of LT-alpha in patients with chronic Chagas' disease.

Main Methods:

  • Genotyping of the LT-alpha (+252) single-nucleotide polymorphism using PCR-RFLP in 284 subjects.
  • Quantification of LT-alpha expression via ELISA in supernatants and flow cytometry on T lymphocytes.
  • Analysis of LT-alpha expression in relation to Trypanosoma cruzi antigen stimulation.

Main Results:

  • Carriers of LT-alpha genotypes GG and GA showed a significantly higher risk (2.8x and 2.4x, respectively) of developing cardiac Chagas' disease compared to genotype AA.
  • Individuals with the G allele exhibited higher LT-alpha production.
  • LT-alpha was predominantly expressed by CD8(+) T lymphocytes, both spontaneously and upon T. cruzi stimulation.

Conclusions:

  • Genetic variations in LT-alpha are associated with an increased susceptibility to cardiac Chagas' disease.
  • LT-alpha plays a significant biological role in the inflammatory processes underlying cardiac manifestations of chronic Chagas' disease.
  • CD8(+) T cells are a primary source of LT-alpha in the context of Chagas' disease.

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