Demetris, AJ

Fujisaki, S

Murase, N

Starzl, TE

Tanabe, M

Todo, S

PubMed

Name not available

Effects of preformed antibodies induced by whole blood transfusion on small bowel transplantation

D-Scholarship@Pitt

Effects of Preformed Antibodies Induced by Whole Blood Transfusion on Small Bowel Transplantation S. FUjisaki, N. Murase, A.J. Demetris, M. Tanabe, S. Todo, and T.E. Starzl ALTHOUGH pretransplant donor-specific transfu-sions (DSn have been effective in prolonging sub-sequent allograft survival. alloreactive antibodies are also produced after sensitization with DST. The purpose of this study was to examine the inftuence of blood transfusion on small bowel transplantation (SBTx). MATERIALS AND METHODS Using inbred male LEW (RTl 1), BN CRTl"). ACI CRTI"). and PYG CRT! 0) rats weighing 200 to 300 g. orthotopic SBTx was periormed as described previously. I Donor-specific or third-party heparinized whole blood 0.0 mLl was given 7 days before transplantation. As a control. SBTx was periormed in untrans-fused recipients. Furthermore. the effect of blood transfusion on the incidence of graft versus host disease (GYHDl was examined using LEW-to-BN SBTx, in which fatal GYHD occurs under FKS06 immunosuppression. l BN recipients received either LEW, PYG. whole blood. or no transfusion 7 days before LEW small bowel grafting. FKS06 (Fujisawa Pharm Co Ltd. Osaka. Japan) was given intramuscularly at a dose of 0.64 mglkgld for 14 postoperative days. Serum samples for Iymphocytoto,uc antibody (LAb) assay were obtained from ACI rats 7 days after PYG blood transfusion. To investigate the specificity of the preformed LAbs induced by blood transfusion. the sera were further absorbed with donor (PYG) or syngeneic (ACI) red blood cells (RBCs). which are known to carry suriace class I mlYor histocompatibility complex (MHC) antigenic determinants. A complement fixing LAb assay was periormed using unfractionated donor or third·party strain lymphocytes as targets according to the method described previ-ously.J In the LEW-ta-BN combination. percentages of donor cells in the recipient circulation were examined. Recipient peripheral blood lymphocytes were stained with monoclonal antibody (MAb) 163. which is specific for the RTt.AI antigen on LEW (kindly provided by Dr H. W. Kunz. University of Pittsburgh. Depart· ment of Pathology) and were analyzed using a FACScan flow cytometer. Statistical analysis was pcriormed using the Mann-Whitney U test. RESULTS DST significantly (P < .05) prolonged the survival of PVG recipients of ACI grafts (median survival 14.0 days. n = 12). LEW recipients of ACI grafts (median survival 16.5 days. n = 6). and BN recipients of LEW grafts (median survival 25.5 days. n = 6) when compared with those without DST (median survival 7.5. 5.5. and 12.5 days. respectively; n = 6 for each group). However. in the LEW-to-ACI combination. animals with DST developed severe graft damage soon after transplantation and two of six (33.3%) animals died within 3 days. suggesting that antibody-mediated rejection occurred in these animals. Surprisingly. the same changes were observed when ACI animals transfused with third-party (PVG) blood received LEW intestinal grafts and three of six (50.0%) died within 3 days. Similar results were obtained after PVG-to-ACI transplants. Six of eight (75.0%) recipients with DST and one of six (16.7%) recipients with third-party (LEW) blood transfusion died within 3 days. Macroscopically. early graft damage was observed in all animals; however. some animals that were able to recover from this early damage showed prolonged survival. LAb assay showed that sera from PVG blood transfused ACI rats were able to kill lymphocytes from donor (PVG) and all third-party strains (LEW. BN. and sm. When sera were absorbed with donor (PVG) RBCs to remove anti-bodies against donor MHC class I. LAb titer was slightly reduced from 211 to 210 against donor (PVG) and from 210 to 29 against third-party (LEW) lymphocytes. The same degree of decrease in LAb titer was also seen after syngeneic RBC absorption. suggesting that the reduction after RBC absorption was not significant and was caused by sample dilution during the procedure. All FK506-treated BN recipients of LEW grafts died of GVHD with a median survival of 32.0 days (n = 8). In contrast. when BN recipients received donor (LEW) and third-party (PVG) blood transfusion 7 days before grafting, animals did not show any signs of GVHD and survived for a median of 85.5 days (n = 12) and 92.0 days (n = 9), respectively. Four of 12 (33.3%) recipients pretreated with LEW blood transfusion and two of nine (22.2%) with PVG blood died of leakage or obstruction in intestinal anasto-moses early after transplantation. These complications were thought to be an immunological event mediated by preformed antibodies. According to ftow cytometric anal-ysis. circulating donor lymphocytes reached 10% in un-transfused recipients 6 to 7 days after SBTx. but donor or third-party blood transfusion totally eliminated donor lym-phocytes from the circulation. These findings explained the absence of GVHD in blood-transfused animals. From the Pittsburgh Transplantation Institute, University of Pitts· burgh Medical Center. Pittsburgh. Pennsylvania. Supported by research grants from the Veterans Administration and project grant No. DK29961 from the National Institutes of Health. Bethesda. Maryland. Address reprint requests to Thomas E. Slarzl. MD, PhD. Pitts· burgh Transplantation Institute. University of Pittsburgh Medical Center. 3601 Fifth Ave. Pittsburgh, PA 15213. £' 1994 by Appleton & Lange 0041-1345/94/$3.00/+0 1528 Transplantation Proceedings, Vol 26. No 3 (June), 1994: pp 1528-1529 PPJl PREFORMED ANTIBODIES DISCUSSION Although LAb production after blood transfusion has been described,1.4 damage caused by these antibodies was not reported after heart, kidney. or liver transplantation. 3,$.6 This study shows that hyperacute rejection of small bowel grafts occurs not only in donor-specific blood-transfused recipients. as reported by Gundlach et al.$ but also in third-party blood-transfused recipients. Results of in vitro LAb assay confirm that antibodies produced in blood-transfused animals are not blood donor MHC class I specific and are cytotoxic to lymphocytes from many rat strains. LAbs induced by blood transfusion have been shown to be of both IgG and IgM class and have low affinity to kidney and liver tissues.3,4 However. this study s~ggests that they may have high affinity to the lymphoid-nch small bowel graft. A distinctive feature of small bowel grafts is the exis-tence of specialized endothelial cells lining the high endo-theli~ venules (HEV) in lymph nodes and Peyer's patches. Specific cell-ta-cell recognition systems between lympho-._------ --- --- --- -_._--- -- ----- -1529 cytes and endothelial cells of HEV mediate migration of lymphocytes from the bloodstream to lymphoid tissues. LAbs produced by blood transfusion may have direct reactivity to endothelial cells of HEV. The nature of antibodies induced by blood transfusion and the mechanisms of damage seen only in small bowel graft are under investigation. REFERENCES I. Murase N. Demetris AJ, Kim 00. et al: Surgery 108:880 f~ • 2. Murase N, Demetris AJ, Woo J. et al: Transplantation 55: 1 1993 • 3. Furuya T. Murase N. Nakamura K. et al: Hepatology 16:141.5. 1992 4. Downey WE III, Baldwin WM Ill. Sanfilippo F: Transplan-tation 49:160. 1~ 5. Gundlach M. Oluwole SF. O'Agati V. et al: Transplantation 53:613. 1992 6. Hutchinson IV. Morris PJ: Transplantation 41:166.1986 

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Effects of preformed antibodies induced by whole blood transfusion on small bowel transplantation

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