The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome

Anat R. Tambur, Salpy V. Pamboukian, Maria Rosa Costanzo, Nancy D. Herrera, Stephanie Hope Dunlap, Michelle Montpetit, Alain Heroux

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Background. The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Methods. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1,2,3,6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9±1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Results. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6±1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Conclusions. Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Original languageEnglish (US)
Pages (from-to)1019-1025
Number of pages7
JournalTransplantation
Volume80
Issue number8
DOIs
StatePublished - Oct 27 2005

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Heart Transplantation
Allografts
Antibodies
HLA-A Antigens
Immunoglobulin Isotypes
HLA Antigens
Coronary Angiography
Serum
Immunosuppression
Antibody Formation
Ischemia
Transplantation
Tissue Donors
Transplants

Keywords

  • HLA-directed antibodies
  • Heart transplant
  • Panel reactive antibodies
  • Transplant outcome

ASJC Scopus subject areas

  • Transplantation

Cite this

The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. / Tambur, Anat R.; Pamboukian, Salpy V.; Costanzo, Maria Rosa; Herrera, Nancy D.; Dunlap, Stephanie Hope; Montpetit, Michelle; Heroux, Alain.

In: Transplantation, Vol. 80, No. 8, 27.10.2005, p. 1019-1025.

Research output: Contribution to journalArticle

Tambur, Anat R. ; Pamboukian, Salpy V. ; Costanzo, Maria Rosa ; Herrera, Nancy D. ; Dunlap, Stephanie Hope ; Montpetit, Michelle ; Heroux, Alain. / The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome. In: Transplantation. 2005 ; Vol. 80, No. 8. pp. 1019-1025.
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abstract = "Background. The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Methods. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1,2,3,6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9±1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Results. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4{\%}), and class II in 11 patients (15.5{\%}). The majority of donor recipient pairs were HLA mismatched (4.6±1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Conclusions. Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.",
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T1 - The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome

AU - Tambur, Anat R.

AU - Pamboukian, Salpy V.

AU - Costanzo, Maria Rosa

AU - Herrera, Nancy D.

AU - Dunlap, Stephanie Hope

AU - Montpetit, Michelle

AU - Heroux, Alain

PY - 2005/10/27

Y1 - 2005/10/27

N2 - Background. The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Methods. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1,2,3,6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9±1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Results. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6±1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Conclusions. Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

AB - Background. The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Methods. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1,2,3,6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9±1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Results. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6±1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Conclusions. Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

KW - HLA-directed antibodies

KW - Heart transplant

KW - Panel reactive antibodies

KW - Transplant outcome

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