Rheumatic heart disease: mediation by complex immune events

Area of Science:

• Immunology
• Cardiovascular Medicine
• Microbiology

Background:

• Rheumatic fever (RF) is an autoimmune disease triggered by Streptococcus pyogenes infection.
• Rheumatic heart disease (RHD), a severe complication, causes chronic valvular damage in 30-45% of RF patients.
• Genetic susceptibility plays a role in RF and RHD development.

Purpose of the Study:

• To investigate genes conferring susceptibility to RF and RHD.
• To understand the role of molecular mimicry in RHD pathogenesis.
• To analyze the involvement of T cell responses and cytokine profiles in RHD.

Main Methods:

• Identification of autoantigens involved in molecular mimicry.
• Analysis of T cell populations (CD4+) and their cytokine production (TNF-alpha, IFN-gamma, IL-4) in heart tissue.
• Comparison of cytokine profiles in myocarditis and valve lesions.

Main Results:

• Molecular mimicry involves cross-reactions between streptococcal antigens and human proteins like cardiac myosin and vimentin.
• Antigen-driven CD4+ T cell expansions producing TNF-alpha and IFN-gamma are implicated in rheumatic heart lesions.
• While IL-4 producing cells are present in the myocardium, they are scarce in RHD valve lesions.

Conclusions:

• The Th1/Th2 cytokine balance is crucial for resolving myocarditis in RF.
• Low levels of IL-4 in RHD valve lesions likely contribute to progressive and irreversible valvular damage.
• Understanding these immune mechanisms may inform RHD prevention and treatment strategies.