LL-37 IgG levels link to prior MI, reduced LVEF, and altered T cells in ACS
Background
Elevated LL-37 IgG levels are implicated in inflammatory conditions, particularly in acute coronary syndrome (ACS), where immune complexes formed with LL-37 may propagate immunothrombosis. The binding of LL-37 to LDL is also relevant, as LDL autoantibodies contribute to ACS risk. Understanding the role of LL-37 IgG in ACS could uncover novel diagnostic biomarkers and therapeutic targets for this leading cause of mortality, given the limitations of current risk stratification and treatment strategies for recurrent events.
Study Design
Researchers utilized three distinct human cohorts to investigate LL-37 IgG levels. First, a cohort without acute disease was used to compare IgG reactivity to native (nLDL), LL-37 complexed with LDL (LL-37_LDL), and free LL-37. Second, N=500 samples from the AZACS (Azithromycin in ACS) study were analyzed for LL-37 IgG levels and their association with clinical characteristics. Third, an ACS cohort was evaluated for the association of LL-37 IgG with left ventricular ejection fraction (LVEF) and T follicular cell responses to LL-37 stimulation of peripheral blood mononuclear cells (PBMCs).
Results
In the initial cohort, LL-37 IgG levels were significantly higher compared to both LL-37_LDL IgG and nLDL IgG. Analysis of the AZACS cohort (N=500) revealed that LL-37 IgG levels were significantly higher in subjects with a history of prior myocardial infarction (MI). Furthermore, LL-37 IgG levels showed a negative correlation with blood pressure in this cohort. In the third ACS cohort, a negative association was observed between LL-37 IgG and LVEF, indicating a potential link to cardiac function. The study also found altered T follicular cell responses: > There was significantly reduced CD8+CD25+CXCR5+ T follicular regulatory cells, while CD8+CD137+CXCR5+ Tf-like cells remained constant, in response to LL-37 stimulation of PBMCs. This suggests a specific immune cell dysregulation associated with increased LL-37 IgG levels in ACS.
Key Findings
- LL-37 IgG levels are significantly higher than LL-37_LDL IgG and nLDL IgG in a non-acute disease cohort.
- LL-37 IgG levels are significantly higher in ACS subjects with prior myocardial infarction (N=500).
- LL-37 IgG levels negatively correlate with blood pressure in the AZACS cohort (N=500).
- A negative association exists between LL-37 IgG levels and LVEF in an ACS cohort.
- LL-37 stimulation reduces
CD8+CD25+CXCR5+T follicular regulatory cells in ACS patients.
Why It Matters
Identifying LL-37 IgG as a potential biomarker for ACS could significantly enhance risk stratification, especially for patients prone to recurrent myocardial infarction or those with compromised cardiac function. This finding suggests LL-37 IgG levels could serve as a prognostic indicator for adverse outcomes like reduced LVEF. While this is an observational study, it lays groundwork for future research into immunomodulatory therapies targeting the LL-37 pathway in ACS. For biohackers and clinicians, understanding this immune-mediated component of ACS opens avenues for exploring interventions that modulate LL-37 activity or its immune complexes, although a usable protocol is still far from development.
ll-37
acute-coronary-syndrome
myocardial-infarction
inflammation
immunology
biomarker