LL ‐37 IgG levels are associated with clinical characteristics and T follicular cell response in acute coronary syndrome in adults

Elevated LL‐37 IgG levels are implicated in inflammatory conditions and immune complexes formed with LL‐37 potentially propagate immunothrombosis in acute coronary syndrome (ACS). The reported binding of LL‐37 to LDL may be relevant in this context given that LDL autoantibodies are implicated in ACS risk. In this report, three distinct cohorts were used to evaluate immunologic characteristics, clinical relevance, and potential mechanisms of elevated LL‐37 IgG levels in ACS. First, evaluation of IgG reactive to native (n) LDL and LL‐37 complexed with LDL (LL‐37_LDL) in a cohort without acute disease demonstrated significantly higher levels of LL‐37 IgG compared to LL‐37_LDL IgG and nLDL IgG. Next, evaluation of LL‐37 IgG levels in samples ( N = 500) from the AZACS study (Azithromycin in ACS) and population‐level associations with clinical characteristics showed that LL‐37 IgG levels were significantly higher in subjects who had prior myocardial infarction and were negatively correlated with blood pressure. Third, an ACS cohort showed a negative association of LL‐37 IgG with LVEF. There was also significantly reduced CD8 + CD25 + CXCR5 + T follicular (Tf) regulatory cells with constant CD8 + CD137 + CXCR5 + Tf‐like cells in response to LL‐37 stimulation of peripheral blood mononuclear cells suggesting the association of Tf cells with increased LL‐37 IgG levels in ACS.