Abstract 12771: When Auto-Antibodies Potentiate: The Paradoxical Signalling Role of Anti-HSP27 Auto-Antibody Immune Complexes Improves Athero-Protection

Introduction: While we recently demonstrated that elevated serum levels of the Heat Shock Protein (HSP27) are athero-protective (JACC 2013), we are cognizant of the presence of anti-HSP27 auto-antibodies in human serum that, intuitively, might attenuate the salutary functions of this protein. Interestingly, we note higher levels of anti-HSP27 auto-antibodies in healthy controls compared to CAD patients. Hypothesis: Taking an iconoclastic perspective, we posit that auto-antibodies to HSP27 function to enhance the athero-protective effects of HSP27. Methods / Results: Briefly, we reassessed a number of the mechanistic published parameters of the athero-protective effects of HSP27 but now in the presence of anti-HSP27 auto-antibodies. Conclusion: Anti-HSP27 auto-antibodies enhance the athero-protective effects of HSP27 by augmenting internalization of the protein, increasing NF-kB signalling and unexpectedly producing a less inflammatory cellular milieu. Hence, there is the potential to develop HSP27 immunization strategies for the prevention and/or treatment of atherosclerosis.