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De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation.
J Heart Lung Transplant. 2014 Dec; 33(12):1288-94.JH

Abstract

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.

Authors+Show Affiliations

Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: morrellmr@upmc.edu.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Department of Pharmacy and Therapeutics, University of Pittsburgh, Pittsburgh, Pennsylvania.Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.Division of Pulmonary Allergy, and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.

Pub Type(s)

Journal Article
Observational Study

Language

eng

PubMed ID

25443870

Citation

Morrell, Matthew R., et al. "De Novo Donor-specific HLA Antibodies Are Associated With Early and High-grade Bronchiolitis Obliterans Syndrome and Death 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. 1288-94.
Morrell MR, Pilewski JM, Gries CJ, et al. De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. J Heart Lung Transplant. 2014;33(12):1288-94.
Morrell, M. R., Pilewski, J. M., Gries, C. J., Pipeling, M. R., Crespo, M. M., Ensor, C. R., Yousem, S. A., D'Cunha, J., Shigemura, N., Bermudez, C. A., McDyer, J. F., & Zeevi, A. (2014). De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation, 33(12), 1288-94. https://doi.org/10.1016/j.healun.2014.07.018
Morrell MR, et al. De Novo Donor-specific HLA Antibodies Are Associated With Early and High-grade Bronchiolitis Obliterans Syndrome and Death After Lung Transplantation. J Heart Lung Transplant. 2014;33(12):1288-94. PubMed PMID: 25443870.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - De novo donor-specific HLA antibodies are associated with early and high-grade bronchiolitis obliterans syndrome and death after lung transplantation. AU - Morrell,Matthew R, AU - Pilewski,Joseph M, AU - Gries,Cynthia J, AU - Pipeling,Matthew R, AU - Crespo,Maria M, AU - Ensor,Christopher R, AU - Yousem,Samuel A, AU - D'Cunha,Jonathan, AU - Shigemura,Norihisa, AU - Bermudez,Christian A, AU - McDyer,John F, AU - Zeevi,Adriana, Y1 - 2014/08/23/ PY - 2014/02/28/received PY - 2014/06/25/revised PY - 2014/07/19/accepted PY - 2014/12/3/entrez PY - 2014/12/3/pubmed PY - 2015/7/29/medline KW - bronchiolitis obliterans syndrome KW - death KW - donor-specific antibody KW - human leukocyte antigen KW - lung transplant SP - 1288 EP - 94 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: 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. SN - 1557-3117 UR - https://www.unboundmedicine.com/medline/citation/25443870/De_novo_donor_specific_HLA_antibodies_are_associated_with_early_and_high_grade_bronchiolitis_obliterans_syndrome_and_death_after_lung_transplantation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1053-2498(14)01285-6 DB - PRIME DP - Unbound Medicine ER -