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De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation.
J Heart Lung Transplant. 2014 Dec; 33(12):1273-81.JH

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

25130554

Citation

Safavi, Shahideh, et al. "De Novo Donor HLA-specific Antibodies Predict Development of Bronchiolitis Obliterans Syndrome After Lung Transplantation." The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, vol. 33, no. 12, 2014, pp. 1273-81.
Safavi S, Robinson DR, Soresi S, et al. De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant. 2014;33(12):1273-81.
Safavi, S., Robinson, D. R., Soresi, S., Carby, M., & Smith, J. D. (2014). De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 33(12), 1273-81. https://doi.org/10.1016/j.healun.2014.07.012
Safavi S, et al. De Novo Donor HLA-specific Antibodies Predict Development of Bronchiolitis Obliterans Syndrome After Lung Transplantation. J Heart Lung Transplant. 2014;33(12):1273-81. PubMed PMID: 25130554.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - De novo donor HLA-specific antibodies predict development of bronchiolitis obliterans syndrome after lung transplantation. AU - Safavi,Shahideh, AU - Robinson,Derek R, AU - Soresi,Simona, AU - Carby,Martin, AU - Smith,John D, Y1 - 2014/07/21/ PY - 2013/09/16/received PY - 2014/07/15/revised PY - 2014/07/16/accepted PY - 2014/8/19/entrez PY - 2014/8/19/pubmed PY - 2015/7/29/medline KW - Luminex-xmap KW - MFI KW - bronchiolitis obliterans syndrome KW - donor-specific antibodies KW - lung transplantation SP - 1273 EP - 81 JF - The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation JO - J. Heart Lung Transplant. VL - 33 IS - 12 N2 - 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. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/25130554/De_novo_donor_HLA_specific_antibodies_predict_development_of_bronchiolitis_obliterans_syndrome_after_lung_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(14)01227-3 DB - PRIME DP - Unbound Medicine ER -