PMID- 25443870
OWN - NLM
STAT- MEDLINE
DCOM- 20150728
LR  - 20220330
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 33
IP  - 12
DP  - 2014 Dec
TI  - De novo donor-specific HLA antibodies are associated with early and high-grade 
      bronchiolitis obliterans syndrome and death after lung transplantation.
PG  - 1288-94
LID - S1053-2498(14)01285-6 [pii]
LID - 10.1016/j.healun.2014.07.018 [doi]
AB  - BACKGROUND: The development of human leukocyte antigen (HLA) antibody responses 
      has been associated with worse clinical outcomes, such as bronchiolitis 
      obliterans syndrome (BOS) and death, in lung transplant recipients (LTRs). 
      However, the role of donor-specific HLA antibody (DSA) responses as a risk factor 
      for poor outcomes remains controversial. METHODS: We prospectively screened 445 
      LTRs for DSA at our institution at the time of surveillance bronchoscopies for 
      the first 2 years after transplantation between 2003 and 2008, and evaluated 
      clinical outcomes. For this purpose, we used the combination of panel-reactive 
      antibodies (PRA) by enzyme-linked immunosorbent assay (ELISA) and the Luminex 
      single-antigen bead (SAB) assay (One Lambda, Canoga Park, CA). RESULTS: We 
      detected de novo DSA (dnDSA) in 58 of 445 (13%) LTRs in our cohort. Freedom from 
      BOS was significantly reduced in LTRs with dnDSA versus those without dnDSA (p < 
      0.001). Using a Cox proportional hazards model, the development of dnDSA was 
      associated with a significantly increased hazard ratio (HR = 6.59 [4.53 to 9.59]; 
      p < 0.001) for BOS and high-grade BOS (Stage >/= 2) (HR = 5.76 [3.48 to 9.52]; p < 
      0.001). Freedom from death was significantly reduced in LTRs with dnDSA (p < 
      0.001), including mortality attributable to BOS (HR = 9.86 [4.91 to 19.78]; p < 
      0.001). CONCLUSIONS: Taken together, our findings provide evidence that dnDSA is 
      associated with accelerated BOS kinetics and severity, as well as death due to 
      BOS after lung transplantation. In addition, these data support regular 
      monitoring for the development of dnDSA in LTRs and underscore the need for novel 
      strategies to mitigate the increased risk of poor outcomes associated with dnDSA.
CI  - Copyright (c) 2014 International Society for Heart and Lung Transplantation. 
      Published by Elsevier Inc. All rights reserved.
FAU - Morrell, Matthew R
AU  - Morrell MR
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: morrellmr@upmc.edu.
FAU - Pilewski, Joseph M
AU  - Pilewski JM
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Gries, Cynthia J
AU  - Gries CJ
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Pipeling, Matthew R
AU  - Pipeling MR
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Crespo, Maria M
AU  - Crespo MM
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Ensor, Christopher R
AU  - Ensor CR
AD  - Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, 
      Pennsylvania.
FAU - Yousem, Samuel A
AU  - Yousem SA
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
FAU - D'Cunha, Jonathan
AU  - D'Cunha J
AD  - Division of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, 
      Pennsylvania.
FAU - Shigemura, Norihisa
AU  - Shigemura N
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Bermudez, Christian A
AU  - Bermudez CA
AD  - Division of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, 
      Pennsylvania.
FAU - McDyer, John F
AU  - McDyer JF
AD  - Division of Pulmonary Allergy, and Critical Care Medicine, University of 
      Pittsburgh, Pittsburgh, Pennsylvania.
FAU - Zeevi, Adriana
AU  - Zeevi A
AD  - Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
LA  - eng
GR  - R01 AI079175/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Observational Study
DEP - 20140823
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Antibodies, Anti-Idiotypic)
RN  - 0 (Biomarkers)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antibodies, Anti-Idiotypic/*metabolism
MH  - Biomarkers/metabolism
MH  - Bronchiolitis Obliterans/*epidemiology/immunology/*mortality
MH  - Bronchoscopy
MH  - Cross-Sectional Studies
MH  - Female
MH  - Follow-Up Studies
MH  - HLA Antigens/*immunology
MH  - Humans
MH  - Lung/immunology/pathology
MH  - *Lung Transplantation
MH  - Male
MH  - Middle Aged
MH  - Postoperative Period
MH  - Prognosis
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Survival Rate
MH  - *Tissue Donors
OTO - NOTNLM
OT  - bronchiolitis obliterans syndrome
OT  - death
OT  - donor-specific antibody
OT  - human leukocyte antigen
OT  - lung transplant
EDAT- 2014/12/03 06:00
MHDA- 2015/07/29 06:00
CRDT- 2014/12/03 06:00
PHST- 2014/02/28 00:00 [received]
PHST- 2014/06/25 00:00 [revised]
PHST- 2014/07/19 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/07/29 06:00 [medline]
AID - S1053-2498(14)01285-6 [pii]
AID - 10.1016/j.healun.2014.07.018 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2014 Dec;33(12):1288-94. doi: 
      10.1016/j.healun.2014.07.018. Epub 2014 Aug 23.