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. 2020 Apr;20(4):1028-1038.
doi: 10.1111/ajt.15687. Epub 2019 Dec 24.

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation

Hrishikesh S Kulkarni  1 , Kevin Tsui  2 , Suraj Sunder  1 , Alex Ganninger  1 , Laneshia K Tague  1 , Chad A Witt  1 , Derek E Byers  1 , Elbert P Trulock  1 , Ruben Nava  3 , Varun Puri  3 , Daniel Kreisel  3 , Thalachallour Mohanakumar  4 , Andrew E Gelman  3   5 , Ramsey R Hachem  1
Affiliations

Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation

Hrishikesh S Kulkarni et al. Am J Transplant. 2020 Apr.

Abstract

Factors contributing to donor-specific HLA antibody (DSA) development after lung transplantation have not been systematically evaluated. We hypothesized that the isolation of Pseudomonas aeruginosa in respiratory specimens would increase the risk of DSA development. Our objective was to determine the risk of DSA development associated with the isolation of Pseudomonas aeruginosa after lung transplantation. We conducted a single-center retrospective cohort study of primary lung transplant recipients and examined risk factors for DSA development using Cox regression models. Of 460 recipients, 205 (45%) developed DSA; the majority developed Class II DSA (n = 175, 85%), and 145 of 205 (71%) developed DSA to HLA-DQ alleles. Univariate time-dependent analyses revealed that isolation of Pseudomonas from respiratory specimens, acute cellular rejection, and lymphocytic bronchiolitis are associated with an increased risk of DSA development. In multivariable analyses, Pseudomonas isolation, acute cellular rejection, and lymphocytic bronchiolitis remained independent risk factors for DSA development. Additionally, there was a direct association between the number of positive Pseudomonas cultures and the risk of DSA development. Our findings suggest that pro-inflammatory events including acute cellular rejection, lymphocytic bronchiolitis, and Pseudomonas isolation after transplantation are associated with an increased risk of DSA development.

Keywords: alloantibody; antibody biology; clinical research/practice; graft survival; immunobiology; infection and infectious agents - bacterial; lung (allograft) function/dysfunction; lung transplantation/pulmonology.

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Conflict of interest statement

DISCLOSURE

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

Figure 1:
Figure 1:. Flow diagram: study screening and eligibility.
Derivation of the study cohort. Flowchart of lung transplant recipients and application of eligibility criteria that resulted in the final study cohort stratified by whether they developed donor-specific antibodies (DSA), and whether they cleared it.
Figure 2:
Figure 2:. Freedom from donor-specific antibodies (DSA) after lung transplantation (LTx).
Kaplan-Meier survival methods estimated the proportion of recipients in whom DSA had not occurred at follow-up after lung transplantation (LTx). The numbers below the x-axis time points represent those at risk. Cohorts consisted of primary LTx reported from January 1, 2008 and December 31, 2015, with follow-up through December 31, 2018. Analyses censored for end of study follow-up and loss to follow-up.
Figure 3:
Figure 3:. Characteristics of donor-specific antibodies (DSA).
This graph represents the specificity of donor-specific antibodies (DSA) present in those recipients transplanted between January 1, 2008 and December 31, 2015, with follow-up through December 31, 2018 (n=205), represented as a proportion (out of 100%). Each recipient may have more than one DSA and thus, may have contributed to more than one bar.
See this image and copyright information in PMC

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References

    1. Chambers DC, Cherikh WS, Goldfarb SB, et al. The International Thoracic Organ Transplant Registry of the International Society for Heart and Lung Transplantation: Thirty-fifth adult lung and heart-lung transplant report-2018; Focus theme: Multiorgan Transplantation. J Heart Lung Transplant. 2018;37(10):1169–1183. - PubMed
    1. Kulkarni HS, Cherikh WS, Chambers DC, et al. Bronchiolitis obliterans syndrome-free survival after lung transplantation: An International Society for Heart and Lung Transplantation Thoracic Transplant Registry analysis. J Heart Lung Transplant. 2019;38(1):5–16. - PMC - PubMed
    1. Royer P-J, Olivera-Botello G, Koutsokera A, et al. Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms. Transplantation. 2016;100(9):1803–1814. - PubMed
    1. Hachem RR. Humoral responses after lung transplantation. Curr Opin Organ Transplant. 2016;21(3):267–271. - PubMed
    1. 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):1288–1294. - PubMed

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