The VEC antigen system is an important immunogen in the pathogenesis of rejection. Our CURRENT function of acting as a service laboratory to screen for the monocyte/VEC antibody for over 30 transplant centers will be markedly restricted and only problem cases will be evaluated on an individual basis. Such cases will include hyperacute rejection in the absence of lymphocytotoxic antibody and HLA identical transplants who reject. A workshop on monocyte and VEC antigens will be organized. Sera made available through the reference laboratory and the workshop will aid in the development of our typing tray for VEC antigens. An expanded sera screening program will improve our current typing tray and support the prospective study on the significance of VEC typing to be carried out at the UNIVERSITY OF ROCHESTER, University of California at San Francisco, University of Wisconsin and University of Michigan, AND SYRACUSE UNIVERSITY. The VEC typing AND MONOCYTE CROSSMATCH WILL BE PERFORMED ONLY AT THE UNIVERSITY OF ROCHESTER. VEC typed patients will be tracked for 2 years for clinical outcome and for development of anti-VEC antibody. Risk factors in transplantation, VEC typing, the development of posttransplant sensitization to VEC and HLA antigens and graft outcome will be subjected to multivariant analysis. An understanding of the expression of the VEC antigens on different blood vessels and in different organs will be studied. We have noted that 16% of highly sensitized patients do not contain antibody to THE VEC OF THAT donor. This suggests that some sensitization may be directed to lymphocyte restricted antigens and not transplant antigens (HLA, VEC). THEREFORE, THE SIGNIFICANCE OF ANTI T CELL ANTIBODY WILL BE COMPARED TO ANTI-VEC ANTIBODY BY: 1) the presence in highly sensitized patients of donor specific T cell lymphocytotoxic antibody on current sera will be compared to the presence of donor specific anti-VEC antibody using the same cadaveric donor blood vessels as targets. 2) THE CLINICAL COURSE OF PATIENTS WITH NO ANTIBODY TO DONOR T OR B CELLS BUT WITH EITHER A NEGATIVE OR POSITIVE DONOR SPECIFIC VEC CROSSMATCH WILL BE COMPARED. If our preliminary observations are confirmed, it may A) make possible the transplantation of some """"""""sensitized"""""""" patients on the basis that such sensitization is directed towards lymphocyte """"""""specific"""""""" antigens and not transplant relevant (HLA, VEC, ABO) antigens; B) AVOID TRANSPLANTING PATIENTS WHO ARE SENSITIZED TO DONOR VEC ANTIGENS IN THE ABSENCE OF SENSITIZATION TO CLASS I OR CLASS II ANTIGENS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK032088-05A2
Application #
3230562
Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Project Start
1982-07-01
Project End
1993-03-31
Budget Start
1989-04-01
Budget End
1990-03-31
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Rochester
Department
Type
School of Medicine & Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627