Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function

Stephen H. Leech, Paul J. Mather, Howard J. Elsen, Lleana L. Pina, Kenneth B. Margulies, Alfred A. Bove, Valluvan Jeevanandam

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Although there is increasing evidence that mismatched donor HLA antigens are associated with a lowering of survival of human cardiac allografts, the effect of antibodies that bind those antigens is less clear. The existence of lymphocytotoxic antibodies prior to cardiac transplantation has been associated with a poor outcome in the majority of reports of relevant studies, as has their appearance post-transplantation. But how such antibodies, especially those with HLA specificity, cause poor outcomes has been poorly understood. The purpose of this study was to investigate the effect of anti-HLA antibodies appearing in the circulation after human orthotopic heart transplantation. Such antibodies were identified by a standard microlymphocytotoxicity technique using panels of frozen lymphocytes from normal donors who had been tissue typed. Of 74 patients transplanted over a 12-month period, 4 (5.4%) developed alloantibodies specific for mismatched donor HLA antigens. The first patient developed antibodies to HLA-A23 and B44 together with poor ventricular function and vascular rejection requiring retransplantation within 4 months. The other patients (3) developed antibodies specific for HLA-DQ antigens and experienced variable numbers of episodes of cellular rejection with no evidence of vascular rejection on endomyocardial biopsy. Two of these three patients died (8 and 11 months post-transplant) after three and six rejection episodes, respectively. The one surviving patient had seven rejection episodes and continues to have poor ventricular function 18 months post-transplant. We conclude that alloantibodies specific for mismatched donor HLA antigens may have a deleterious effect on the outcome of the human cardiac allograft and should be monitored closely post-transplant. Furthermore, such antibodies may mediate effects on the transplanted heart which are not detectable in specimens obtained by endomyocardial biopsy.

Original languageEnglish (US)
Pages (from-to)639-645
Number of pages7
JournalClinical Transplantation
Volume10
Issue number6 II
StatePublished - Dec 1996
Externally publishedYes

Fingerprint

Transplantation
Tissue Donors
Antibodies
HLA Antigens
Isoantibodies
Ventricular Function
Heart Transplantation
Transplants
Allografts
Blood Vessels
HLA-B44 Antigen
HLA-DQ Antigens
Biopsy
Antilymphocyte Serum
Anti-Idiotypic Antibodies
Lymphocytes
Antigens

Keywords

  • Graft rejection
  • Heart transplantation
  • HLA antibodies
  • HLA-DQ

ASJC Scopus subject areas

  • Transplantation
  • Immunology

Cite this

Leech, S. H., Mather, P. J., Elsen, H. J., Pina, L. L., Margulies, K. B., Bove, A. A., & Jeevanandam, V. (1996). Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function. Clinical Transplantation, 10(6 II), 639-645.

Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function. / Leech, Stephen H.; Mather, Paul J.; Elsen, Howard J.; Pina, Lleana L.; Margulies, Kenneth B.; Bove, Alfred A.; Jeevanandam, Valluvan.

In: Clinical Transplantation, Vol. 10, No. 6 II, 12.1996, p. 639-645.

Research output: Contribution to journalArticle

Leech, SH, Mather, PJ, Elsen, HJ, Pina, LL, Margulies, KB, Bove, AA & Jeevanandam, V 1996, 'Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function', Clinical Transplantation, vol. 10, no. 6 II, pp. 639-645.
Leech SH, Mather PJ, Elsen HJ, Pina LL, Margulies KB, Bove AA et al. Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function. Clinical Transplantation. 1996 Dec;10(6 II):639-645.
Leech, Stephen H. ; Mather, Paul J. ; Elsen, Howard J. ; Pina, Lleana L. ; Margulies, Kenneth B. ; Bove, Alfred A. ; Jeevanandam, Valluvan. / Donor-specific HLA antibodies after transplantation are associated with deterioration in cardiac function. In: Clinical Transplantation. 1996 ; Vol. 10, No. 6 II. pp. 639-645.
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