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Related Experiment Videos

Rheumatic fever: from innate to acquired immune response.

L Guilherme1, J Kalil

  • 1Heart Institute (InCor), School of Medicine, Univaersity of São Paulo, São Paulo, Brazil. luizagui@usp.br

Annals of the New York Academy of Sciences
|September 7, 2007
PubMed
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Rheumatic fever and rheumatic heart disease involve complex immune responses. Genetic factors and specific immune cells contribute to autoimmune heart damage following S. pyogenes infection.

Area of Science:

  • Immunology
  • Genetics
  • Cardiology

Background:

  • Rheumatic fever (RF) and rheumatic heart disease (RHD) arise from S. pyogenes infection.
  • Genetic factors, including HLA class II alleles and Tumor Necrosis Factor-alpha (TNF-alpha), are implicated in RF/RHD development.
  • Mannose-binding lectin (MBL) deficiency is observed in some RHD patients, highlighting innate immunity's role.

Purpose of the Study:

  • To investigate the complex genetic and immunological mechanisms underlying autoimmune lesions in rheumatic heart disease.
  • To explore the role of specific genes and immune cell responses in the pathogenesis of RF/RHD.

Main Methods:

  • Analysis of HLA class II alleles and TNF-alpha gene polymorphisms in RHD patients.
  • Investigation of MBL deficiency in Brazilian RHD patients.

Related Experiment Videos

  • T cell clone analysis recognizing cardiac myosin peptides and cross-reactive M5 peptide.
  • Cytokine profiling (TNF-alpha, IFN-gamma, IL-4, IL-10) in myocardial and valvular tissues.

    • Main Results:

    • Associations found between TNFA-308 allele and valvular lesions in RHD patients.
    • HLA-DR7 positive antigen-presenting cells from RHD patients recognized a specific heart-tissue cross-reactive peptide (M5).
    • Predominance of pro-inflammatory cytokines (TNF-alpha, IFN-gamma) and regulatory cytokine IL-10 in affected heart tissues, with scarce IL-4.

    Conclusions:

    • The development of autoimmune lesions in RF/RHD is complex, involving both innate and adaptive immune responses.
    • Specific genetic variations and T cell recognition of cardiac antigens contribute to valvular damage.
    • The cytokine milieu in heart tissue plays a critical role in the autoimmune process of RF/RHD.