Immune Response to LL-37 Peptide Distinguishes Heart Disease Types

Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of morbidity and mortality, characterized by chronic inflammation and plaque buildup in arteries. The immune system plays a critical role in its development and progression, but specific immune signatures that differentiate various ASCVD phenotypes remain poorly understood. This study aimed to investigate whether adaptive immune responses to the autoantigen LL-37 could serve as a biomarker to distinguish different clinical presentations of ASCVD.

Patients with ACS exhibited significantly higher T-cell proliferative responses to LL-37 compared to both CAD patients and healthy controls, with a 2.8-fold increase in CD4+ T-cell proliferation in ACS vs. controls (p<0.001). Serum anti-LL-37 IgG antibody levels were also markedly elevated in ACS patients, showing a 43% higher mean concentration than in CAD patients (p=0.003). > The most striking finding was that a combined biomarker panel of anti-LL-37 IgG titers and LL-37-specific IFN-γ (interferon-gamma, a pro-inflammatory cytokine) production achieved an 88% accuracy in differentiating ACS from stable CAD patients. Conversely, stable CAD patients showed a modest, but statistically significant, 1.5-fold increase in IL-10 (interleukin-10, an anti-inflammatory cytokine) production by LL-37-stimulated T-cells compared to healthy controls (p=0.02), suggesting a different immune regulatory profile. No significant differences were observed in anti-LL-37 IgM levels across the groups.