Ann Thorac Surg 2001;71:47-48
© 2001 The Society of Thoracic Surgeons
Invited commentary: original article: cardiovascular
Invited commentary
Richard A. Hopkins, MDa,
Diane Hoffman–Kim, PhDb,
Mary S. Maish, MDc
a Professor and Chief, Cardiothoracic Surgery, Brown University School of Medicine, Director, Collis Cardiac Surgical Research Laboratory, Rhode Island Hospital, The Miriam Hospital, Hasbro Children’s Hospital, Providence, RI 02906, USA
b Assistant Professor, Department of Surgery, Division of Cardiac Surgery, Brown University School of Medicine, Lead Scientist, Collis Cardiac Surgical Research Laboratory, Providence, RI 02906, USA
c Roddy Scholar in Cardiac Surgery Research, Collis Cardiac Surgical Laboratory, Department of Surgery, Brown University School of Medicine, Providence, RI 02906, USA
e-mail: rahopkins{at}lifespan.org
This study by Shaddy and colleagues from Primary Children’s Medical Center in Salt Lake City is extraordinarily interesting and despite the low number of patients involved is a significant contribution to the evolving literature on immunology of cryopreserved homograft valve conduit transplants. The first point of interest is how difficult this study was to pursue given the potential for significant complications. One-third of the prospective study patients (including parents) approached, declined to take part in the study. Of the 20 patients actually entered into the study, only 13 completed a course of Azathioprine or control. Two of the patients in the Azathioprine group were withdrawn for infectious complications, thus five of the ten patients initially entered into the Azathioprine arm sustained infectious complications, equivalent to the 50%, three of six, patients who actually completed the Azathioprine course but with infectious complications.
The second point of significant interest is that this group clearly demonstrated that panel reactive antibodies against histocompatibility leukocyte antigen (HLA) Class I and Class II alloantigens developed in patients following valve transplantation and were sustained for the duration of the study (3 months). This observation along with other similar studies performed around the world (as cited in their bibliography) clearly indicate that human cryopreserved allograft cardiac valves are immunogenic and induce specific alloantibodies. In the 1970’s and 1980’s, there were theories that cryopreserved heart valves had some form of "immunologic privilege" associated with minimal or absent antibody and cellular immune response. This study is yet one more nail in the coffin of those preposterous theories.
The final point and the central conclusion of this study is that a course of moderate Azathioprine has no effect on panel reactive antibodies: "Azathioprine does not reduce the alloimmune HLA antibody response, nor does it decrease the occurrence of allograft dysfunction." Since there were no reductions in the antibody levels during the three months of the study, the authors appropriately concluded that "immunosuppression with Azathioprine has no effect on the humoral immune response or the functional outcome of the allograft valve in the short term." In response to the misperceptions of the early 1980’s about immune privilege, there has evolved some anecdotal suggestions that low dose short or medium term immunosuppression might be useful for extending the durability of homograft valve transplants and various protocols have been promulgated around the world, but not appropriately subjected to prospective randomized studies. Hopefully, this study will put an end to such uncontrolled exposure of children to dangerous immunosuppressive protocols which appears to be a futile attempt to render the patient non-responsive to the transplanted antigenic proteins. Currently, there is no place for such ad hoc immunosuppressive protocols in the absence of prospective randomized studies accomplished with appropriate and thorough informed consent. The authors are to be congratulated for attempting this difficult but critically important research.
Related Article
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Prospective randomized trial of azathioprine in cryopreserved valved allografts in children
- Robert E. Shaddy, Linda M. Lambert, Thomas C. Fuller, Tracie Profaizer, Dixie D. Thompson, Shawna I. Baker, Karen A. Osborne, and John A. Hawkins
Ann. Thorac. Surg. 2001 71: 43-47.
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