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J Heart Lung Transplant. 2014 Dec;33(12):1273-81. doi: 10.1016/j.healun.2014.07.012. Epub 2014 Jul 21.

De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.

Author information

1
Department of Transplantation, Harefield Hospital, Middlesex, UK.
2
Mathematics Department, University of Sussex, Brighton, Middlesex, UK.
3
Tissue Typing Laboratory, Heart Science Centre, Harefield Hospital, Harefield, Middlesex, UK. Electronic address: j.smith@rbht.nhs.uk.

Abstract

BACKGROUND:

Bronchiolitis obliterans syndrome (BOS) is the major cause of late graft failure after lung transplantation. The objective was to determine whether de novo donor human leukocyte antigen (HLA)-specific antibodies (DSA) are associated with the development of BOS or patient survival. Data were analyzed from 188 lung transplant recipients with a follow-up period up to 8 years.

METHODS:

HLA antibody monitoring was performed at 3-month intervals post-transplant at routine outpatient clinic attendances and during the investigation of any acute deterioration. HLA antibody data were available for 148 patients; 66 (45%) had produced HLA antibodies after transplant, of which 38 (26%) were DSA and 28 (19%) non-donor-specific HLA antibodies.

RESULTS:

De novo DSA was associated with development of BOS Stage 1 (BOS1; hazard ratio [HR] = 2.302, p = 0.0015), BOS2 (HR = 3.627, p < 0.0001) and BOS3 (HR = 5.736, p < 0.0001). De novo persistent DSA correlated strongly with shorter time to onset of BOS3 (HR = 6.506, p = 0.0001). There was a significant reduction in patient survival associated with de novo DSA (HR = 1.886, p = 0.047). In multivariable analyses, de novo DSA was an independent predictor for development of all stages of BOS as well as an independent predictor of poor patient survival.

CONCLUSIONS:

De novo DSA is a major risk factor for progression to BOS and shorter patient survival. Treatments to remove antibodies or limit antibody-mediated damage could be considered when DSA are first detected. However, a randomized, controlled trial of treatment options would enable a clearer understanding of the benefits, if any, of antibody-removal therapies.

KEYWORDS:

Luminex-xmap; MFI; bronchiolitis obliterans syndrome; donor-specific antibodies; lung transplantation

PMID:
25130554
DOI:
10.1016/j.healun.2014.07.012
[Indexed for MEDLINE]

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