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Immunoglobulin g lymphocytotoxic antibodies in clinical liver transplantation: Studies toward further defining their significance

Authors

  • Rafael Mañez,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Robert H. Kelly,

    1. Pathology, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Makoto Kobayashi,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
    2. Pathology, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Shunichi Takaya,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Oscar Bronsther,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • David Kramer,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
    2. Anesthesiology/Critical Care Medicine, Pittsburgh Transplant Institute, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Rene J. Duquesnoy,

    1. Pathology, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Yuichi Iwaki,

    1. Pathology, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • John J. Fung,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Thomas E. Starzl,

    1. Departments of Surgery, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
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  • Anthony J. Demetris MD

    Corresponding author
    1. Pathology, University of Pittsburgh School of Medicine, and The Veterans Administration Medical Center, Pittsburgh, PA
    • Department of Pathology, Division of Transplantation, Biomedical Science Tower, Room E1548, Pittsburgh, PA 15261
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Abstract

Twenty-two consecutive liver allograft recipients, who tested positive for immunoglobulin G (IgG) lympho-cytotoxicity were subjected to pretransplantion and posttransplantation immunologic monitoring of antidonor IgG lymphocytotoxic antibody titers, total hemolytic complement activity (CH100), circulating immune complexes (CIC), and platelet counts in an effort to improve our understanding of the preformed antibody state in clinical hepatic transplantation. Ten contemporaneous liver transplant recipients whose crossmatch results were negative and who experienced severe hepatocellular damage early after transplantation were included as controls. Crossmatch test results were negative 1 day after transplantation and during the 1 month follow-up remained negative in 14 of 22 (64%) sensitized recipients, most of whom had relatively low (≦ 1:16) antidonor IgG antibody titers before transplantation. After transplantation, this group and the control group experienced no thrombocytopenia, no increase of CIC, and a gradual increase in CH100 activity that reached normal levels within 1 week. A strong negative correlation between prothrombin time (PT) and CH100 activity in these groups of patients suggested that changes in CH100 activity (P < 0.0005) were tightly linked to liver synthetic function. In contrast, the crossmatch test results remained positive after transplantation in 8 of 22 (36%) sensitized recipients, all of whom had relatively high (> 1:32 to 1024) pretransplantation titers of antidonor IgG antibodies. After transplantation these patients developed a syndrome that was characterized by decreased CH100 activity and increased CIC compared with pretransplantation levels and refractory thrombocytopenia that was associated with a 50% allograft failure rate because of biopsy-proven humoral and acute (cellular) rejection. Moreover, the lack of a strong negative correlation between PT and CH100 activity (P = 0.1) in this group of patients suggested that the hypocomplementemia was not tightly linked to liver synthetic function. Before transplantation, determination of anti—donor antibody class (IgG) and titer alone showed a strong negative predictive value (100%) but less than optimal positive predictive value (67%) for identifying patients who experienced the posttransplantation syndrome described above. Therefore, evaluation of platelet counts, CH100 activity, CIC, persistence of anti-donor antibodies and results of a liver biopsy performed after transplantation assisted in identifying sensitized liver allograft recipients who suffered the adverse consequences of the preformed antibody state.

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