The role of donor-specific antibodies in acute cardiac allograft dysfunction in the absence of cellular rejection

Nowell M. Fine, Richard C. Daly, Nisha Shankar, Soon J. Park, Sudhir S. Kushwaha, Manish J. Gandhi, Naveen Luke Pereira

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear. METHODS: We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50% and a decrement of 10% or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls. RESULTS: There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P<0.05) but remained unchanged over time for controls. Six (60%) patients with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P<0.01). There were 4 (40%) patients with AAD with no DSA or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.

Original languageEnglish (US)
Pages (from-to)229-238
Number of pages10
JournalTransplantation
Volume98
Issue number2
DOIs
StatePublished - Jul 27 2014

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Allografts
Tissue Donors
Antibodies
Transplants
Antigens
Stroke Volume
Morbidity

Keywords

  • Allograft dysfunction
  • Antibody-mediated rejection
  • Donor-specific antibodies
  • Heart transplant

ASJC Scopus subject areas

  • Transplantation

Cite this

The role of donor-specific antibodies in acute cardiac allograft dysfunction in the absence of cellular rejection. / Fine, Nowell M.; Daly, Richard C.; Shankar, Nisha; Park, Soon J.; Kushwaha, Sudhir S.; Gandhi, Manish J.; Pereira, Naveen Luke.

In: Transplantation, Vol. 98, No. 2, 27.07.2014, p. 229-238.

Research output: Contribution to journalArticle

Fine, Nowell M. ; Daly, Richard C. ; Shankar, Nisha ; Park, Soon J. ; Kushwaha, Sudhir S. ; Gandhi, Manish J. ; Pereira, Naveen Luke. / The role of donor-specific antibodies in acute cardiac allograft dysfunction in the absence of cellular rejection. In: Transplantation. 2014 ; Vol. 98, No. 2. pp. 229-238.
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abstract = "BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear. METHODS: We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50{\%} and a decrement of 10{\%} or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls. RESULTS: There were 10 (3{\%}) patients with AAD, 4 (40{\%}) had DSA detectable by SAB assay compared to 16 (53{\%}) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P<0.05) but remained unchanged over time for controls. Six (60{\%}) patients with AAD and 1 (3{\%}) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P<0.01). There were 4 (40{\%}) patients with AAD with no DSA or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.",
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AU - Kushwaha, Sudhir S.

AU - Gandhi, Manish J.

AU - Pereira, Naveen Luke

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N2 - BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear. METHODS: We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50% and a decrement of 10% or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls. RESULTS: There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P<0.05) but remained unchanged over time for controls. Six (60%) patients with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P<0.01). There were 4 (40%) patients with AAD with no DSA or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.

AB - BACKGROUND: Acute allograft dysfunction (AAD) is an important cause of morbidity among heart transplant recipients. The role of donor-specific antibodies (DSAs) in AAD, with the increasing use of single antigen bead (SAB) assays that have improved the ability to detect DSA, remains unclear. METHODS: We retrospectively reviewed 329 heart transplant recipients followed up at our institution. AAD was defined as an acute decline in left ventricular ejection fraction to less than 50% and a decrement of 10% or higher compared to baseline in the absence of cellular rejection. Patients with AAD were compared with matched 30 heart transplant controls. RESULTS: There were 10 (3%) patients with AAD, 4 (40%) had DSA detectable by SAB assay compared to 16 (53%) controls (P=0.43). Peak DSA mean fluorescent intensity (MFI) levels were significantly higher at baseline (class I and class II) in AAD compared to controls. DSA MFI values increased at the time of AAD and returned to baseline values during follow-up for these patients with AAD (P<0.05) but remained unchanged over time for controls. Six (60%) patients with AAD and 1 (3%) control had antibody-mediated rejection (AMR) by endomyocardial biopsy (P<0.01). There were 4 (40%) patients with AAD with no DSA or AMR. CONCLUSIONS: AAD after heart transplant is a heterogeneous process characterized by 1) AMR and DSA, 2) AMR but no DSA, and 3) no AMR or DSA. The presence of DSA is not associated with AAD, but the quantity assessed by MFI levels may play a role.

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KW - Antibody-mediated rejection

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KW - Heart transplant

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