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Humoral immunity to bone allografts: Development of IGG to donor alloantigens is associated with delayed union and poor function
8
Abstracts
C-6.5
HUMORAL IMMUNITY TO BONE ALLOGRAFTS: DEVELOPMENT OF IGG TO DONOR ALLOANTIGENS IS ASSOCIATED WITH DELAYED UNION AND POOR FUNCTION. K Nelson, J Hoekema, W Yadock, S Chloupek, R Bazzano, NA Sundling, DM Strong, and EU Conrad III. Immunogenetics Laboratory and Northwest Tissue Center, Puget Sound Blood Program, and Univ. of Washington Department of Orthopaedics, Seattle, WA. Recipients of osteochondral or osseous allografts have been reported to develop antibody to allogeneic HLAantigens. However, due to high incidence of perioperative transfusion in these patients, the role of the allograft in inducing sensitization is unclear. The specificity of the antibody for donor HLA antigens has not been established due to the lack of donor lymphoid cells for typing or crossmatching. A prospective study was designed to study the specificity of humoral immunity in these patients and its association with graft function. Lymphoid cells from donors and were cryopreserved. Recipient cells and serum were obtained prior to transplant and at 6 mo. intervals post-transplant and cryopreserved. Synovial fluid was removed when clinically indicated, fluid and infiltrating cells were cryopreserved. Typing for HLA class I and class II antigens was performed using standard techniques. The presence of antibody to donor alloantigens was detected using a two-color indirect immunofluorescence assay with donor or autologous lymphocytes as targets and was analysed on a flow cytometer. IgG which bound to donor T and/or B lymphocytes but not to autologous cells was interpreted as evidence of donor-specific alloantibody. To date, 21 patients have been followed for up to 27 months post-transplant. Pediatric recipients numbered 17, 4 were adults. Twenty of the 21 had no evidence of donor-specific alloantibody prior to transplant. Of these 20, 7 did not develop antibody during this study. All 7 were recorded with good to excellent function, one experienced delayed union. Of the thirteen who developed donor-specific IgG antibody post-transplant, 10 experienced poor function or delayed union. Three had good function although all 3 required revision due to fixation failure. The association of the development of alloantibody specific for donor antigens with poor outcome of the allograft was significant at p<0.05 by Fisher's exact test.
C-6.3
HEART TRANSPLANT REJECTION STRONGLY CORRELATES WITH HLA MISMATCH. S Sheldon, P Haselton, NA Yonan, AN Rahman, AK Deiraniya, CS Campbell, NH Brooks and PA Dyer. NW Regional Tissue Typing Laboratory, St. Mary's Hospital, MANCHESTER UK The effect of HLA incompatibility on heart transplant (HTPX) survivals has proved difficult to evaluate due to the strong bias towards transplants with a high degree of HLA mismatch (MM). This bias is a result of the relatively short cold ischaemia time which has traditionally deterred HTPX centres from pursuing prospective HLA matching policies. With accurate rapid prospective HLA matching now feasible we examined the role of HLA mismatching in HTPX on endomyocardial biopsies (EMB) from 157 consecutive orthotopic HTPX performed from April 1987 to August 1993. EMB grade > = 2 was used as the cut off point for definition of clinically significant rejection. We find that HTPX with least HLA-DR MM have a highly significantly reduced frequency of EMB grades > =2. This HLA-DR mismatching effect is observed with analysis of EMB results from the first three months post transplant, the first year post transplant and with the total data. This study clearly shows that HTPX matched at the HLA-DR locus have a HLA-DR HTPX EMB % Grades significantly reduced incidence of EMB MM No. No. > = 2 MM grades indicative of m a i n t e n a n c e immunosuppression being insufficient for management of rejection. Given the results 13 148 18 0 of this study and that high quality HLA 53 797 29 1 typing can now be achieved from donor peripheral blood we identify an urgent need 91 1624 34 2 for the widespread application of prospective < 0.0000~ HLA matching in HTPX.
Abstracts
C-6.5
HUMORAL IMMUNITY TO BONE ALLOGRAFTS: DEVELOPMENT OF IGG TO DONOR ALLOANTIGENS IS ASSOCIATED WITH DELAYED UNION AND POOR FUNCTION. K Nelson, J Hoekema, W Yadock, S Chloupek, R Bazzano, NA Sundling, DM Strong, and EU Conrad III. Immunogenetics Laboratory and Northwest Tissue Center, Puget Sound Blood Program, and Univ. of Washington Department of Orthopaedics, Seattle, WA. Recipients of osteochondral or osseous allografts have been reported to develop antibody to allogeneic HLAantigens. However, due to high incidence of perioperative transfusion in these patients, the role of the allograft in inducing sensitization is unclear. The specificity of the antibody for donor HLA antigens has not been established due to the lack of donor lymphoid cells for typing or crossmatching. A prospective study was designed to study the specificity of humoral immunity in these patients and its association with graft function. Lymphoid cells from donors and were cryopreserved. Recipient cells and serum were obtained prior to transplant and at 6 mo. intervals post-transplant and cryopreserved. Synovial fluid was removed when clinically indicated, fluid and infiltrating cells were cryopreserved. Typing for HLA class I and class II antigens was performed using standard techniques. The presence of antibody to donor alloantigens was detected using a two-color indirect immunofluorescence assay with donor or autologous lymphocytes as targets and was analysed on a flow cytometer. IgG which bound to donor T and/or B lymphocytes but not to autologous cells was interpreted as evidence of donor-specific alloantibody. To date, 21 patients have been followed for up to 27 months post-transplant. Pediatric recipients numbered 17, 4 were adults. Twenty of the 21 had no evidence of donor-specific alloantibody prior to transplant. Of these 20, 7 did not develop antibody during this study. All 7 were recorded with good to excellent function, one experienced delayed union. Of the thirteen who developed donor-specific IgG antibody post-transplant, 10 experienced poor function or delayed union. Three had good function although all 3 required revision due to fixation failure. The association of the development of alloantibody specific for donor antigens with poor outcome of the allograft was significant at p<0.05 by Fisher's exact test.
C-6.3
HEART TRANSPLANT REJECTION STRONGLY CORRELATES WITH HLA MISMATCH. S Sheldon, P Haselton, NA Yonan, AN Rahman, AK Deiraniya, CS Campbell, NH Brooks and PA Dyer. NW Regional Tissue Typing Laboratory, St. Mary's Hospital, MANCHESTER UK The effect of HLA incompatibility on heart transplant (HTPX) survivals has proved difficult to evaluate due to the strong bias towards transplants with a high degree of HLA mismatch (MM). This bias is a result of the relatively short cold ischaemia time which has traditionally deterred HTPX centres from pursuing prospective HLA matching policies. With accurate rapid prospective HLA matching now feasible we examined the role of HLA mismatching in HTPX on endomyocardial biopsies (EMB) from 157 consecutive orthotopic HTPX performed from April 1987 to August 1993. EMB grade > = 2 was used as the cut off point for definition of clinically significant rejection. We find that HTPX with least HLA-DR MM have a highly significantly reduced frequency of EMB grades > =2. This HLA-DR mismatching effect is observed with analysis of EMB results from the first three months post transplant, the first year post transplant and with the total data. This study clearly shows that HTPX matched at the HLA-DR locus have a HLA-DR HTPX EMB % Grades significantly reduced incidence of EMB MM No. No. > = 2 MM grades indicative of m a i n t e n a n c e immunosuppression being insufficient for management of rejection. Given the results 13 148 18 0 of this study and that high quality HLA 53 797 29 1 typing can now be achieved from donor peripheral blood we identify an urgent need 91 1624 34 2 for the widespread application of prospective < 0.0000~ HLA matching in HTPX.