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Human complement receptor type 1 (CR1) protein levels and genetic variants in chronic Chagas Disease

Thaisa Lucas Sandri1,2, Kárita Cláudia Freitas Lidani1, Fabiana Antunes Andrade1

  • 1Laboratory of Molecular Immunopathology, Federal University of Paraná, Curitiba, Brazil.

Scientific Reports
|January 12, 2018
PubMed

Insights

Complement receptor 1 (CR1) levels are lower in Chagas Disease (CD) patients. Specific CR1 variants and haplotypes are linked to T. cruzi infection and chagasic cardiomyopathy risk.

Area of Science:

  • Immunology
  • Genetics
  • Infectious Diseases

Background:

  • Complement system is crucial in immunity and disease pathogenesis, including Chagas Disease (CD).
  • Human complement receptor 1 (CR1) influences pathogen entry and clearance of immune complexes.
  • CR1 exon 29 variants are linked to CR1 expression and disease susceptibility.

Purpose of the Study:

  • To investigate the association between CR1 plasma levels, CR1 exon 29 variants, and Chagas Disease in a Brazilian cohort.
  • To determine the role of CR1 in the immunopathogenesis and clinical presentation of chronic CD.

Main Methods:

  • Assessed CR1 plasma levels using ELISA in 232 chronic CD patients and 104 healthy controls.
  • Sequenced CR1 exon 29 to identify variants and haplotypes.
  • Analyzed statistical associations between CR1 levels, variants, haplotypes, and CD status/clinical outcomes.

Main Results:

  • CD patients exhibited significantly lower CR1 plasma levels compared to controls (p < 0.0001).
  • CR1 variants rs1704660G, rs17047661G, and rs6691117G were associated with CD and in high linkage disequilibrium.
  • The CR1*AGAGTG haplotype correlated with T. cruzi infection (OR 3.99), and CR1*AGGGTG with chagasic cardiomyopathy risk (OR 12.15).

Conclusions:

  • This study reveals a significant association between reduced CR1 levels and specific CR1 variants/haplotypes with Chagas Disease.
  • Findings provide novel insights into CR1's role in the development and clinical manifestations of chronic Chagas Disease.

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