TY - JOUR
T1 - Human leukocyte antigens antibodies after lung transplantation
T2 - Primary results of the HALT study
AU - Hachem, Ramsey R.
AU - Kamoun, Malek
AU - Budev, Marie M.
AU - Askar, Medhat
AU - Ahya, Vivek N.
AU - Lee, James C.
AU - Levine, Deborah J.
AU - Pollack, Marilyn S.
AU - Dhillon, Gundeep S.
AU - Weill, David
AU - Schechtman, Kenneth B.
AU - Leard, Lorriana E.
AU - Golden, Jeffrey A.
AU - Baxter-Lowe, Lee Ann
AU - Mohanakumar, Thalachallour
AU - Tyan, Dolly B.
AU - Yusen, Roger D.
N1 - Funding Information:
This study was funded by the National Institutes of Health, National Heart, Lung, and Blood Institute (Grant Number: HL105412).
Funding Information:
We conducted a prospective observational cohort study of lung transplant recipients at 6 centers in the United States to determine the cumulative incidence of posttransplant DSA, describe their characteristics, and assess their impact on clinical outcomes. The National Institutes of Health funded the study as a 2-year R34 grant (HL 10542). Each site aimed to prescreen/screen all lung transplant candidates placed on the United Network for Organ Sharing (UNOS) waiting list at the institution. Study personnel screened patients for eligibility (Table E1 in the online data supplement) at the time of listing for transplantation or within the first 10 days after transplantation. Enrollment was initiated on December 1, 2011 and completed on June 30, 2012; follow-up was completed on October 28, 2012. Local institutional review boards at each center approved the study protocol, and all participants provided written informed consent.
Publisher Copyright:
© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2018/9
Y1 - 2018/9
N2 - Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.
AB - Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P =.047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P =.039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.
KW - clinical research/practice
KW - histocompatibility
KW - lung transplantation/pulmonology
KW - major histocompatibility complex (MHC)
KW - monitoring: immune
KW - rejection: T cell mediated (TCMR)
KW - rejection: antibody-mediated (ABMR)
UR - http://www.scopus.com/inward/record.url?scp=85052526898&partnerID=8YFLogxK
U2 - 10.1111/ajt.14893
DO - 10.1111/ajt.14893
M3 - Article
C2 - 29687961
AN - SCOPUS:85052526898
SN - 1600-6135
VL - 18
SP - 2285
EP - 2294
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 9
ER -