Abstract
Background. We determined the role of donor-specific antibodies (DSA) and antibodies (Abs) to self-antigens, collagen-V (Col-V), and K-alpha 1-Tubulin (KAT) in pathogenesis of acute antibody-mediated rejection (AMR) and cardiac allograft vasculopathy (CAV) after human heart transplantation (HTx).
Methods. One hundred thirty-seven HTx recipients, with 60 early period (<= 12 months) and 77 late period (>12 months), were enrolled in this study. Circulating DSA was determined using LUMINEX. Abs against Col-I, II, IV, V, and KAT were measured using ELISA. Frequency of CD4+Thelper cells(CD4+Th) secreting interferon (IFN)-gamma, interleukin (IL)-5, -10, or -17 specific to self-antigens were determined using Enzyme Linked Immunosorbent Spot assay.
Results. A significant association between AMR and DSA was demonstrated. Development of DSA in AMR patients correlated well with the development of auto-Abs to Col-V (AMR[+]: 383+/-72 mu g/mL, AMR[-]: 172+/-49 mu g/mL, P=0.033) and KAT (AMR[+]: 252+/-49 mu g/mL, AMR[-]: 61+/-21 mu g/mL, P=0.014). Patients who developed AMR demonstrated increased frequencies of CD4+Th secreting IFN-gamma and IL-5 with reduction in IL-10 specific for Col-V/KAT. Patients diagnosed with CAV also developed DSA and auto-Abs to Col-V (CAV[+]: 835+/-142 mu g/mL, CAV[-]: 242+/-68 mu g/mL, P=0.025) and KAT (CAV[+]: 768+/-206 mu g/mL, CAV[+]: 196+/-72 mu g/mL, P=0.001) with increased frequencies of CD4+Th secreting IL-17 with reduction in IL-10 specific for Col-V/KAT.
Conclusions. Development of Abs to human leukocyte antigens and self-antigens are associated with increases in CD4+Th secreting IFN-gamma and IL-5 in AMR and IL-17 in CAV, with reduction in CD4+Th secreting IL-10 in both AMR and CAV.