Abstract 14071: HSP27 and Anti-HSP27 Autoantibodies: Novel CAD Biomarkers That Non-Invasively Stratified a Medically Underserviced Population

Background: There is an important need to develop reliable, non-invasive biomarkers reflective of coronary artery disease (CAD). Previously, we reported that reduced serum Heat Shock Protein 27 (HSP27) levels measured using an ELISA method are associated with increased 5-year risk of cardiovascular death, MI or CVA. However, we recently noted the presence of HSP27 autoantibodies (AAbs) in serum that effectively obfuscate HSP27 ELISA measurements. Therefore we developed a novel mass spectrometry (MS) method to quantify (true) HSP27 serum levels. Purpose: To determine if serum HSP27 (as measured by MS) and anti-HSP27 AAbs levels correlate with the freedom from CAD. Methods: Serum HSP27 (using MS) and AAb levels were assessed in 242 patients with CAD (e.g., rest angina >20’, ECG changes, ACS, revascularization) or 92 subjects without (Healthy Control, HC). The cohorts consisted of approximately 40% medically underserved individuals. Results: Matching for sex and age, 79 cases in each group were compared. a) The MS HSP27 assay yielded results that paralleled our previous report on the predictive value of HSP27 levels measured by ELISA but were ~100-fold higher. CAD patients had lower Hsp27 (323.8 vs. 377.4 ng/ml; p=0.00067) and anti-Hsp27 levels (25.8 vs. 46.3 units; p=2.9E-6) compared to HC. b) Serial assessment of HSP27 levels did not vary over time (e.g., assays every 6 months) in stable subjects with or without CAD. c) Compared to female HCs, CAD females had lower HSP27 (350.3 vs. 387.9ng/ml; p=0.024) and anti-HSP27 levels (22.3 vs. 49.6 units; p=0.00015). Compared to male HCs, CAD males also had lower HSP27 (314.0 vs. 352.5 ng/ml; p=0.026) and anti-HSP27 levels (28.9 vs. 43.0 units; p=0.0073). d) HSP27 and anti-HSP27 AAbs levels are higher in females age 60 years (p=0.0048, p=0.016); while there were no age differences in males levels (p=0.524 and p=0.776). Conclusion: A novel MS assay for serum Hsp27 levels represent a robust new biomarker for CAD. As well, coupled with our recent in vitro studies on the mechanisms by which AAbs potentiate HSP27 signaling, we established the importance of AAbs as a complimentary biomarker for CAD. Together, these studies highlight the potential for developing HSP27 replacement / immunization therapy.