Systemic Soluble and Cellular Immune Response in Acute Rheumatic Fever and Rheumatic Heart Disease: A Systematic...

Area of Science:

• Immunology
• Cardiovascular Medicine
• Rheumatology

Background:

• Rheumatic heart disease (RHD) is a significant cause of illness in low- and middle-income countries.
• It is the most severe outcome of acute rheumatic fever (ARF), triggered by Streptococcus pyogenes.
• RHD results from molecular mimicry leading to autoimmune cardiac valve damage.

Purpose of the Study:

• To systematically review human studies and identify systemic immune signatures linked to valvular pathology in RHD and ARF.
• To clarify the roles of specific immune cells and mediators in disease pathogenesis.
• To identify potential prognostic markers and therapeutic targets.

Main Methods:

• Systematic review of human studies published between 1977 and 2025.
• Searches conducted across PubMed, LILACS, ScienceDirect, and Web of Science databases.
• Analysis of 29 studies (22 RHD, 7 ARF) focusing on immune signatures and valvular pathology.

Main Results:

• ARF showed elevated IL-6, IL-8, IL-17F, GM-CSF, TNF-α, CXCL10, and increased CD4+ Th1 and MAIT cell activity.
• RHD exhibited a consistent inflammatory-fibrotic profile with increased IL-17, IFN-γ, TNF-α, TGF-β1, Tenascin-C, and prothymosin alpha (ProTα).
• CD4+ and CD8+ T cells were implicated in valve injury, with ProTα correlating with CD8+ cytotoxic activity. Systemic inflammation mirrored local valve damage.

Conclusions:

• T cells and pro-inflammatory cytokines play a central role in RHD pathogenesis.
• Identified immune mediators and cell activities highlight potential prognostic markers.
• Findings provide a basis for developing targeted translational studies and therapeutic strategies for RHD.