Abstract Body (Do not enter title and authors here): Background: Reduced level of IgG autoantibodies specific for the apoB-100 peptide P210 is associated with increased risk for myocardial infarction (MI). However, the underlying mechanism for reduced P210 IgG levels in patients at risk of MI is unknown. Methods: We evaluated the baseline P210 IgG and immune complex (P210 IgG-IC) levels using ELISA of plasma samples of a sub-cohort of volunteers having coronary artery calcium scans (CACS) as part of the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) trial. The sub-cohort selected were those that did not have MI (No MI, N=90) and those that had a future MI (FMI, N=23) during follow-up (13.2±2.1 years). We also evaluated plasma samples collected from patients admitted to Cedars-Sinai for acute coronary syndrome (ACS, N=15). ELISA for P210 IgG and ICs were standardized against a pool of healthy control plasma and expressed as adjusted optical density (Adj OD). Flow cytometry evaluation of CXCR5+ T follicular helper (Tfh) cells that regulate IgG levels was performed in peripheral blood mononuclear cells (PBMCs) from ACS patients (N=8) in response to in vitro stimulation with P210. Specimen and data collection were IRB approved. Results: P210 IgG was significantly lower in FMI patients compared to No MI and ACS patients (FMI=0.6±0.6 vs No MI=1.5±1.6 and ACS=1.4±0.9 Adj OD; P<0.001). Plasma LDL was significantly higher in FMI patients compared to No MI and ACS patients (FMI=160.7±25.2 vs No MI=126.0±40.6 and ACS=114.9±53.4 mg/dL; P<0.0001). Since P210 is a peptide antigen of LDL apolipoprotein apoB-100 and considering that P210 IgG may form ICs with LDL, we evaluated plasma P210 IgG-ICs using a P210 capture monoclonal antibody. The No MI group for P210 IgG-IC ELISA only included subjects with the lowest risk of MI (CACS 0; N=23) to minimize variability within the group. FMI patients had significantly higher P210 IgG-ICs (FMI=3.3±2.4 vs No MI=2.0±2.0 and ACS=2.2±2.9 Adj OD; P<0.01), suggesting P210 IgG may have been depleted in FMI plasma by forming ICs with LDL. CD4+CD154+CXCR5+ Tfh cell response to P210 in PBMCs from ACS patients was significantly reduced compared to cells with no peptide stimulation (P<0.05). Conclusion: The results suggest that increased P210 IgG-IC formation may account for reduced P210 IgG in FMI patients. Reduced CD4+CD154+CXCR5+ Tfh cells in response to P210 stimulation may underly the lack of compensatory increase in P210 IgG in ACS patients.