HLA and MICA allosensitization patterns among patients supported by ventricular assist devices

Medhat Askar, Eileen Hsich, Patrick Reville, Amy S. Nowacki, William Baldwin, Suzanne Bakdash, Jenna Daghstani, Aiwen Zhang, Lynne Klingman, Nicholas Smedira, Nader Moazami, David O. Taylor, Randall C. Starling, Gonzalo Gonzalez-Stawinski

Research output: Contribution to journalArticle

Abstract

Background Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens. Methods We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups. Results Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs 0%, p <0.0001) and higher peak PRA (24% vs 6%, p <0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16% vs 0%, p <0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p <0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14% in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups. Conclusion Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.

Original languageEnglish (US)
Pages (from-to)1241-1248
Number of pages8
JournalJournal of Heart and Lung Transplantation
Volume32
Issue number12
DOIs
StatePublished - Dec 2013
Externally publishedYes

Fingerprint

Heart-Assist Devices
HLA Antigens
Antibodies
Transplants
Antigens
MHC class I-related chain A
Antibody Specificity
Immunoglobulin Isotypes
Immunologic Factors
Graft Survival
Major Histocompatibility Complex
Medical Records
Multivariate Analysis

Keywords

  • Allosensitization
  • Antibody detection
  • Heart transplantation
  • Hla antibodies
  • Mica antibodies
  • Vad

ASJC Scopus subject areas

  • Transplantation
  • Cardiology and Cardiovascular Medicine
  • Pulmonary and Respiratory Medicine
  • Surgery

Cite this

Askar, M., Hsich, E., Reville, P., Nowacki, A. S., Baldwin, W., Bakdash, S., ... Gonzalez-Stawinski, G. (2013). HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. Journal of Heart and Lung Transplantation, 32(12), 1241-1248. https://doi.org/10.1016/j.healun.2013.08.014

HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. / Askar, Medhat; Hsich, Eileen; Reville, Patrick; Nowacki, Amy S.; Baldwin, William; Bakdash, Suzanne; Daghstani, Jenna; Zhang, Aiwen; Klingman, Lynne; Smedira, Nicholas; Moazami, Nader; Taylor, David O.; Starling, Randall C.; Gonzalez-Stawinski, Gonzalo.

In: Journal of Heart and Lung Transplantation, Vol. 32, No. 12, 12.2013, p. 1241-1248.

Research output: Contribution to journalArticle

Askar, M, Hsich, E, Reville, P, Nowacki, AS, Baldwin, W, Bakdash, S, Daghstani, J, Zhang, A, Klingman, L, Smedira, N, Moazami, N, Taylor, DO, Starling, RC & Gonzalez-Stawinski, G 2013, 'HLA and MICA allosensitization patterns among patients supported by ventricular assist devices', Journal of Heart and Lung Transplantation, vol. 32, no. 12, pp. 1241-1248. https://doi.org/10.1016/j.healun.2013.08.014
Askar, Medhat ; Hsich, Eileen ; Reville, Patrick ; Nowacki, Amy S. ; Baldwin, William ; Bakdash, Suzanne ; Daghstani, Jenna ; Zhang, Aiwen ; Klingman, Lynne ; Smedira, Nicholas ; Moazami, Nader ; Taylor, David O. ; Starling, Randall C. ; Gonzalez-Stawinski, Gonzalo. / HLA and MICA allosensitization patterns among patients supported by ventricular assist devices. In: Journal of Heart and Lung Transplantation. 2013 ; Vol. 32, No. 12. pp. 1241-1248.
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abstract = "Background Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens. Methods We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups. Results Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18{\%} vs 0{\%}, p <0.0001) and higher peak PRA (24{\%} vs 6{\%}, p <0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16{\%} vs 0{\%}, p <0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p <0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14{\%} in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups. Conclusion Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.",
keywords = "Allosensitization, Antibody detection, Heart transplantation, Hla antibodies, Mica antibodies, Vad",
author = "Medhat Askar and Eileen Hsich and Patrick Reville and Nowacki, {Amy S.} and William Baldwin and Suzanne Bakdash and Jenna Daghstani and Aiwen Zhang and Lynne Klingman and Nicholas Smedira and Nader Moazami and Taylor, {David O.} and Starling, {Randall C.} and Gonzalo Gonzalez-Stawinski",
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T1 - HLA and MICA allosensitization patterns among patients supported by ventricular assist devices

AU - Askar, Medhat

AU - Hsich, Eileen

AU - Reville, Patrick

AU - Nowacki, Amy S.

AU - Baldwin, William

AU - Bakdash, Suzanne

AU - Daghstani, Jenna

AU - Zhang, Aiwen

AU - Klingman, Lynne

AU - Smedira, Nicholas

AU - Moazami, Nader

AU - Taylor, David O.

AU - Starling, Randall C.

AU - Gonzalez-Stawinski, Gonzalo

PY - 2013/12

Y1 - 2013/12

N2 - Background Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens. Methods We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups. Results Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs 0%, p <0.0001) and higher peak PRA (24% vs 6%, p <0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16% vs 0%, p <0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p <0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14% in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups. Conclusion Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.

AB - Background Ventricular assist devices (VADs) are increasingly being used as a bridge to transplantation and have been implicated as a risk factor for allosensitization to human leukocyte antigens (HLA). We investigate the association between VAD and allosensitization to human leukocyte antigens (HLA) and major-histocompatibility-complex (MHC) class I-related Chain A (MICA) antigens. Methods We considered all patients who received a VAD at our institution between 2000 and 2009; 89 of them had pre-VAD and post-VAD (≤6 months after implant) HLA antibody screening. A control group of non-VAD heart transplant candidates was constructed with at least 2 pre-transplant panel-reactive antibody (PRA) tests within 8 months. Two controls were randomly selected/VAD patient matched for year (n = 178). Patients and controls with available sera from these time-points were tested by Luminex/flow PRA single-antigen beads and by MICA antibody Luminex single-antigen beads. Medical records were reviewed for comparison of pre-transplant immunologic risk factors and post-transplant outcomes between the 2 groups. Results Compared with controls, VAD patients had greater Class I differences between peak and initial PRA (18% vs 0%, p <0.0001) and higher peak PRA (24% vs 6%, p <0.0001). The differences between the 2 groups in Class II were less pronounced than in Class I. Of patients who had single-antigen testing, VAD implantation was significantly associated with development of new HLA antibody specificities (Class I and/or Class II) post-VAD with an increase in calculated PRA (cPRA) post-VAD compared with controls (16% vs 0%, p <0.0001). This risk was still present after adjusting for age, gender, pre-VAD PRA, transfusion and duration of follow-up in a multivariate analysis (p <0.0001 and 0.02, respectively). There were no differences in development of MICA antibodies between the 2 groups (14% in both). There was no significant difference in the incidence of pre-transplant positive T-cell crossmatch, pre-transplant donor-specific HLA antibodies, rejection episodes or graft survival between the 2 groups. Conclusion Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.

KW - Allosensitization

KW - Antibody detection

KW - Heart transplantation

KW - Hla antibodies

KW - Mica antibodies

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