1035-LBP: Development of antibodies to HLA in patients on left ventricular assisting device (LVAD) leads to increased proinflammatory cytokines and immune responses to cardiac self-antigens, Myosin and Vimentin

Aim Recent studies have demonstrated that patients with left ventricular assist devices (LVAD) are at increased risk of development of antibody mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) post heart transplantation (HTx). However, the role of pre-existing antibodies (Abs) to HLA in inducing immune responses to cardiac self-antigens (CSAgs) is yet to be defined. In this study, we determined the kinetics of development of Abs to HLA and immune responses to CSAgs during the pre-transplant period in patients on LVAD. Methods Sera from 70 HTx (40 LVAD, 30 Non-LVAD) were enrolled and serially analyzed for Abs to HLA using Luminex and for CSAgs by ELISA. Serum cytokines (IFN γ , IL-17, IL-1 β and IL-10) were analyzed by LUMINEX. Sera from 32 age and gender matched normal subjects were the controls. Results Among LVAD patients, 22/40 (55% vs. 3.1%, p p p p p  > 0.08) had anti-HLA prior to HTx. In this group, 5/30 (16.7% vs. normal 6.3%, p p γ (2.4 fold), IL-17 (1.9 fold), and IL-1 β (2.7 fold) along with decrease in IL-10 (3.1 fold). Conclusions LVAD patients have increased risk for development of anti-HLA prior to transplantation and anti-HLA positive patients further develop immune responses to CSAgs. LVAD patients with anti-HLA and anti-CSAgs have increased circulating pro-inflammatory cytokines prior to transplant which we hypothesize to play a significant role in the development of AMR and CAV following HTx.