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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.

Publication ,  Journal Article
Morrell, MR; Pilewski, JM; Gries, CJ; Pipeling, MR; Crespo, MM; Ensor, CR; Yousem, SA; D'Cunha, J; Shigemura, N; Bermudez, CA; McDyer, JF; Zeevi, A
Published in: J Heart Lung Transplant
December 2014

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.

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Published In

J Heart Lung Transplant

DOI

EISSN

1557-3117

Publication Date

December 2014

Volume

33

Issue

12

Start / End Page

1288 / 1294

Location

United States

Related Subject Headings

  • Tissue Donors
  • Survival Rate
  • Surgery
  • Risk Factors
  • Retrospective Studies
  • Prospective Studies
  • Proportional Hazards Models
  • Prognosis
  • Postoperative Period
  • Middle Aged
 

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Morrell, M. R., Pilewski, J. M., Gries, C. J., Pipeling, M. R., Crespo, M. M., Ensor, C. R., … Zeevi, A. (2014). 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, 33(12), 1288–1294. https://doi.org/10.1016/j.healun.2014.07.018
Morrell, Matthew R., Joseph M. Pilewski, Cynthia J. Gries, Matthew R. Pipeling, Maria M. Crespo, Christopher R. Ensor, Samuel A. Yousem, 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 33, no. 12 (December 2014): 1288–94. https://doi.org/10.1016/j.healun.2014.07.018.
Morrell MR, Pilewski JM, Gries CJ, Pipeling MR, Crespo MM, Ensor CR, 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 Dec;33(12):1288–94.
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.J Heart Lung Transplant, vol. 33, no. 12, Dec. 2014, pp. 1288–94. Pubmed, doi:10.1016/j.healun.2014.07.018.
Morrell MR, Pilewski JM, Gries CJ, Pipeling MR, Crespo MM, Ensor CR, Yousem SA, D’Cunha J, Shigemura N, Bermudez CA, McDyer JF, Zeevi A. 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):1288–1294.
Journal cover image

Published In

J Heart Lung Transplant

DOI

EISSN

1557-3117

Publication Date

December 2014

Volume

33

Issue

12

Start / End Page

1288 / 1294

Location

United States

Related Subject Headings

  • Tissue Donors
  • Survival Rate
  • Surgery
  • Risk Factors
  • Retrospective Studies
  • Prospective Studies
  • Proportional Hazards Models
  • Prognosis
  • Postoperative Period
  • Middle Aged