TY - JOUR
T1 - Pseudomonas aeruginosa and acute rejection independently increase the risk of donor-specific antibodies after lung transplantation
AU - Kulkarni, Hrishikesh S.
AU - Tsui, Kevin
AU - Sunder, Suraj
AU - Ganninger, Alex
AU - Tague, Laneshia K.
AU - Witt, Chad A.
AU - Byers, Derek E.
AU - Trulock, Elbert P.
AU - Nava, Ruben
AU - Puri, Varun
AU - Kreisel, Daniel
AU - Mohanakumar, Thalachallour
AU - Gelman, Andrew E.
AU - Hachem, Ramsey R.
N1 - Publisher Copyright:
© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2020/4/1
Y1 - 2020/4/1
N2 - 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.
AB - 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.
KW - alloantibody
KW - antibody biology
KW - clinical research/practice
KW - graft survival
KW - immunobiology
KW - infection and infectious agents - bacterial
KW - lung (allograft) function/dysfunction
KW - lung transplantation/pulmonology
UR - http://www.scopus.com/inward/record.url?scp=85076880961&partnerID=8YFLogxK
U2 - 10.1111/ajt.15687
DO - 10.1111/ajt.15687
M3 - Article
C2 - 31677358
AN - SCOPUS:85076880961
SN - 1600-6135
VL - 20
SP - 1028
EP - 1038
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 4
ER -