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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

Insights

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.
  • 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.

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