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Ann Thorac Surg 1998;66:2022-2026
© 1998 The Society of Thoracic Surgeons

Original Articles

Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies

Franciska M.E. Hoekstra, MDa, Marian Witvliet, BScd, Christiaan Y. Knoop, BSca, Claes Wassenaar, MDc, Ad J.J.C. Bogers, MD, PhDb, Willem Weimar, MD, PhDa, Frans H.J. Claas, PhDd

a Department of Internal Medicine I, University Hospital Rotterdam, Rotterdam, the Netherlands
b Department of Thoracic Surgery, University Hospital Rotterdam, Rotterdam, the Netherlands
c Heart Valve Bank, University Hospital Rotterdam, Rotterdam, the Netherlands
d Department of Immunohematology and Blood Bank, University Hospital Leiden, Leiden, the Netherlands

Accepted for publication June 8, 1998.

Address reprint requests to Dr Hoekstra, Department of Internal Medicine I, University Hospital Rotterdam-Dijkzigt, Room Bd 293, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands
e-mail: (hoekstra{at}inw1a2r.nl)

Background. The kinetics of panel reactive antibodies (PRA) and incidence of antibodies directed against human leukocyte antigen (HLA) class II were studied in patients who received a cryopreserved cardiac valve allograft.

Methods. A complement-dependent microlymphocytotoxicity test was used to determine the percentage of panel reactive antibodies. Anti–HLA class II antibodies were measured by two-color fluorescence assays.

Results. The panel reactive antibodies became positive in 25 (78%) of 32 recipients between 1 and 16 months after implantation. Antibodies against HLA class II antigens were detected in 11 (37%) of 30 patients. In 9 (82%) of 11 cases these antibodies were donor specific. The induction of antibodies against donor HLA class II antigens suggests that intact HLA class II antigens are expressed by viable cells within the graft. Dithiothreitol analysis showed that the antibodies were of the immunoglobulin G type. Apparently, the HLA class II antigens are expressed in an immunogeneic way, as activation of specific T-helper cells is essential for the switch from immunoglobulin M to immunoglobulin G antibodies.

Conclusions. Allogeneic valve transplantation is associated with the production of donor-specific anti–HLA class I and II antibodies that could contribute to graft failure. This possibly detrimental effect might be prevented by cross matching in sensitized patients.


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Ann. Thorac. Surg. 1998 66: 2026. [Extract] [Full Text] [PDF]



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