BRYAN, C

DUQUESNOY, RJ

FUNG, JJ

GORDON, RD

KLINTMALM, G

MARKUS, BH

STARZL, TE

VANEK, M

VANTHIEL, D

English

PubMed

D-Scholarship@Pitt

~l Association of HLA Compatibility and Decreased Liver Transplant Survival B.H. Markus, R.J. Duquesnoy, R.D. Gordon, J.J. Fung, M. Vanek, G. Klintmalm, C. Bryan, D. Van Thiel, and T.E. Starzl i.HLA COMPATIBILITY has been widely recognized to improve the outcome of lddneyl.2 and probably heart transplants3 but no beneficial effect has been reported for liver transplants.4-6 Neither pretransplant HLA-specific antibodies nor a positive donor-specific I:[ossmatch seems to decrease liver allograft survival. 7·9 Recent studies have shown HLA-specific alloreactive T cells in lymphocyte cultures grown from hepatic allo-grafts, providing evidence that HLA antigens are involved in cellular immune mechanisms leading to rejection of liver allografts. 10.1 I We have recently reexamined the question of whether HLA compatibility influences liver transplant survival. This paper briefly sum-marizes the results of this analysis, a more detailed report will appear elsewhere. 12 METHODS AND RESULTS This ,(udv was conducted on more than 500 primary grafts and retransplants. The overall actuarial graft sur-vival was 59% at I year and 55% at 2 years. We observed that HLA compatibility was associated with lower sur-vival rates of liver allografts. For the HLA-A locus, liver transplants with zero mismatches (n - 42) did worse than those with one or two mismatched antigens (n - 532). One-year graft survivals were 41.1% and 61.6%, and 2-year graft survivals were 37.5% and 56.7%, respec-tively. The differences between the zero v one and two HLA-A mismatch groups were statistically significant. Although a similar trend was noted for HLA-8 compati-bility, insufficient numbers of zero HLA-8 antigen mis-matches were available for a meaningful statistical analy-sis. Similarly, liver transplants with zero HLA-DR mis-m.'h:nes shared lower survival rates than the group with on~ :lnd two HLA-DR mismatches. The I-year and 2-year graft survivals were 51.9% v 60.3%, and 45.0% v 56.9%, respectively. This study also considered a group of allograft failures in patients who were retransplanted. A total of 119 failures were classified into three diagnostic categories based on clinical and pathologic assessment as previously described.'! These were rejection (n - 53), primary non function (n - 31), and other causes of failure includ-ing vascular thrombosis, infections. and "technical" com-plications (n - 33). The frequency of rejection as the cause of transplant failure was the lowest in liver allo-grafts with zero mismatches. especially for HLA-DR, but also for HLA-A and HLA-B. Increased HLA incompati-bility was associated with higher incidence of rejection. On the other hand, primary non function occurred rela-tively more often with HLA-DR compatible liver trans-plants, whereas the incidence of other causes of liver allograft failure was associated with HLA-A- or -8-compatible liver transplants. DISCUSSION These data demonstrate that HLA compat-ibility is associated with a decreased survival of liver transplants. The effect was noted for both class I antigens of HLA-A and class II antigens of the HLA-DR locus. The present findings are in contrast to the widely reported beneficial effect of HLA compatibility on kidney transplant outcome. I•2 Our inability to demonstrate a beneficial effect of matching for HLA on liver trans-plant survival does not necessarily conflict with the concept that HLA influences trans-plant rejection of liver allografts. This is apparent from our observations that the fre-quency of liver transplant failures due to rejection correlated with the degree of HLA mismatching, especially for HLA-DR. Be-sides transplant rejection induced by HLA From the Division of Clinical Immunopathology and the Department of Surgery, University of Pittsburgh, and the Bay/or University Medica/ Center. Dallas. B.H. Markus is a recipient of a research fellowship from the Deutsche Forschungsgemeinschaft. Address reprint requests to Rene J. Duquesnoy. PhD, Division of Clinical Immunopathology, University of Pittsburgh. Children's Tower. Room 5725. Pittsburgh. PA /5213-3417. © /988 by Grune & Stratton. Inc. oo41-/345j88j2oo/-/013$3.00jO Transplllntation Proc86dings, Vol XX. No 1, Suppl 1 (February), 1988: pp 43-44 43 44 incompatibility, other immunologic mecha-nisms may be responsible for liver transplant failure. These mechanisms could be specific for a variety of antigens, including viral anti-gens, autoantigens, and tissue-specific compo-nents. Particular consideration must be given to the influence of HLA, especially in view of its role in cellular interactions during the immune response. This phenomenon is referred to as major histocompatibility com-plex (MHC) restriction and has been widely observed in human and animal models of immune responsiveness. Many cellular inter-actions during the immune response are HLA restricted, that is, they are efficient only if the cells involved express shared HLA antigens. This MHC restriction (or self-recognition) has been demonstrated in interactions between antigen-presenting cells and T lym-phocytes and in cytotoxic T cell-induced lysis of virus-infected and other antigen-expressing target cells. HLA restriction has been demon-strated for cellular immunity to clinically MARKUS ET AL relevant viral antigens such as hepatitis B virus, cytomegalovirus, and Epstein-Barr viruS. I4-16 During infection, cytotoxic lympho-cyte-mediated damage would probably be more efficient if infected target cells in the allograft express compatible HLA antigens. The phenomenon of HLA restriction has not been extensively studied in autoimmune liver diseases because the antigens involved are largely undefined. However, HLA has been indirectly implemented through its asso-ciation with several liver diseases including chronic active hepatitis and sclerosing cholan-gitis. 17 These processes would not only affect the original liver, but also may contribute to recurrent disease of the transplanted liver, especially from an HLA-compatible donor. Thus, the concept should be raised that HLA compatibility may have a dualistic effect on liver transplant outcome: On one hand it reduces the rejection process, whereas on the other hand, it may enhance other immunologic mechanisms leading to allograft dysfunction. REFERENCES I. Cecka JM: In Terasaki PI (ed) Clinical Kidney Transplants 1986. Los Angeles, UCLA Tissue Typing Laboratory, 1986, p 141 2. OpelzG: Transplant Proc 19:641, 1987 3. Yacoub M, Festenstein p, Doyle p, et al: Transplant Proc 19:2487, 1987 3. Starzl TE, Iwatsuki S, Van Thiel DH, et al: Hepa· tology 2:614, 1982 5. Malatack 11, Zitelli BJ, Gartner JC Jr, et al: Transplant Proc IS: 1292. 1983 6. Markus BH. Fung JJ, Gordon RD, et al: Transplant Proc 19:63, 1987 (suppI3) 7. Starzl TE, Ishikawa M, Putnam CW, et al: Trans-plant Proc 6: 129, 1974 (suppl) 8. Iwatsuki S, Rabin BS, Shaw BW Jr, et al: Trans-plant Proc 16:1427, 1984 9. Gordon RD. Fung 11, Markus BM, et al: Surgery 100:705, 1986 10. Fung 11, Zeevi A, Starzl TE, et al: Hum Immunol 16:182, 1986 II. Markus BH, Fung 11, Zeevi A, et al: Transplant Proc 19:2470, 1987 12. Markus BH, Duquesnoy RJ, Gordon RD, et al: submitted for publication 13. Shaw BW Jr, Gordon RG, Iwatsuki S, et al: Semin Liver Dis 5:394, 1985 14. Quinnan GV Jr, Kirmani N, Esber E, et al: J ImmunoI126:2036,1981 15. Lindsley MD, Torpey DJ III, Rinaldo CR Jr: J Immunol136: 3045, 1986 16. Misko IS, Moss DJ, Pope JH: Proc Nat! Acad Sci USA 77:4247,1980 17. Tiwari JL, Terasaki PI: HLA and disease associa-tions. New York, Springer, 1985 lJ 1 or. enf In idi, stu as me tio lyr ity SUI no; do an we Wt at' stl Ig se: sp xe na in fa af E Se Tr 

ASSOCIATION OF HLA COMPATIBILITY AND DECREASED LIVER-TRANSPLANT SURVIVAL

Markus, BH

Duquesnoy, RJ

Gordon, RD

Fung, JJ

Vanek, M

Klintmalm, G

Bryan, C

Van Thiel, D

Starzl, TE

Name not available

Association of HLA compatibility and decreased liver transplant survival

http://d-scholarship.pitt.edu/4217/1/31735062129824.pdf

ASSOCIATION OF HLA COMPATIBILITY AND DECREASED LIVER-TRANSPLANT SURVIVAL

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