98 Role of Antibodies to HLA, Collagen-V and K-α1-Tubulin in Antibody Mediated Rejection and Cardiac Allograft Vasculopathy

Abstract

Purpose Donor specific antibodies (DSA) to mismatched HLA and cardiac self antigens have been implicated in the pathogenesis of acute and chronic allograft rejection following human adult heart transplantation (HTx). We determined the role of DSA and antibodies (Abs) to self antigens, collagen-V (Col-V) and K-α1-Tubulin (KAT) in the pathogenesis of acute antibody mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) following HTx. Methods and Materials 137 HTx recipients - 60 early period (EP, 12 months) patients were enrolled. Circulating DSA was determined using LUMINEX. Abs against Col-I, II, IV, V and KAT were measured using ELISA. Frequency of CD4+ T helper cells (CD4+Th) secreting IFN-γ, IL-5, IL-10 or IL-17 specific to Col-V or KAT were determined using ELISPOT. Results A significant association between AMR and DSA (AMR(+):78%, AMR(-):18%, p=0.03) and Abs to Col-V (AMR(+): 383±72μg/mL, AMR(-):172±49μg/mL, p=0.033) and KAT (AMR(+): 252±49μg/mL, AMR(-): 61±21μg/mL, p=0.014) was demonstrated. AMR(+) patients demonstrated increased frequencies of CD4+Th cells secreting IFN-γ and IL-5 with reduction in IL-10 specific for Col-V and KAT. CAV(+) patients developed DSA (CAV(+):79%, CAV(-):25%, p=0.03) and Abs to Col-V (CAV(+):835±142μg/mL, CAV(-): 242±68μg/mL, p=0.025) and KAT (CAV(+): 768±206μg/mL, CAV(-): 196±72μg/mL p=0.001) with increased frequencies of CD4+Th cells IL-17 with reduction in IL-10 specific for Col-V and KAT. Conclusions We conclude that development of Abs to HLA and self antigens were associated with marked increases in CD4 T cells secreting IFN-γ and IL-5 specific for self antigens in AMR and IL-17 in CAV with reduction in T cells secreting IL-10 in both AMR and CAV.