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EPITHELIAL SPECIFIC, NON-MHC ANTIBODIES, INDUCE HYPERACUTE REJECTION OF HUMAN LUNG ALLOGRAFTS.
S. Ramachandran Ph.D 1, T. Goers M.D 1, K. Parekh M.D 1, E. Trulock M.D 2, G. Patterson M.D 2 and T. Mohanakumar Ph.D 1,3. 1 Surgery, Washington University School of Medicine ; 2 Cardiothoracic Surgery and 3 Pathology & Immunology, Washington University, St Louis, MO, USA .
Transplantation across ABO incompatibility and positive HLA cross match has been shown to induce hyperacute rejection (HAR) of the transplanted lungs. However, the ability of non-HLA antibodies to induce HAR of transplanted lungs is not well defined.
Sera and lung biopsies from three lung transplant recipients (negative by cross match) undergoing hyperacute rejection were collected prior to and after transplantation. Serum and eluted antibodies from HAR lung was analyzed by FACS and western blot against a panel of human bronchial epithelial cells (HBEC), human aortic endothelial cells (HAEC) and lymphocytes to analyze specific reactivity and complement fixation. Complement deposition in HAR lung was analyzed by C4d ELISA kit.
FACS analyses demonstrated specific reactivity against HBECs but not against PBLs. Sera from these recipients were immunoreactive to 42 kDa polypeptide in HBEC extracts which was not observed against HAECs or lymphocytes indicating the epithelial specificity. Eluted antibodies from the hyperacutely rejected lung were iummunoreactive to the same 42kDa epithelial antigen recognized by sera from the lung transplant recipients. Isotype analysis demonstrated that these antibodies were IgG molecules and were developed prior to transplantation. A significant increase in C4d deposition was also observed in lung biopsies, indicating HAR.
Results obtained from the above experiments demonstrate that preformed anti-epithelial antibodies against a 42 kDa surface antigen in human lung transplant recipients can cause hyperacute rejection of human lung allografts.