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


CONCLUSIONS
Our results suggest that VAD is associated with significant HLA allosensitization independent of common risk factors.
Allogen Laboratories Transplant Center. Electronic address: askarm@ccf.org.
Medhat
M
Askar
Eileen
E
Hsich
Patrick
P
Reville
Amy S
AS
Nowacki
William
W
Baldwin
Suzanne
S
Bakdash
Jenna
J
Daghstani
Aiwen
A
Zhang
Lynne
L
Klingman
Nicholas
N
Smedira
Nader
N
Moazami
David O
DO
Taylor
Randall C
RC
Starling
Gonzalo
G
Gonzalez-Stawinski
D064591:Allografts; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D006680:HLA Antigens / Q000276:immunology*; D006333:Heart Failure / Q000628:therapy*; D016027:Heart Transplantation; D006353:Heart-Assist Devices; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A
HLA antibodies; MICA antibodies; VAD; allosensitization; antibody detection; heart transplantation