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Prevalence of antibodies to lung self-antigens (Kα1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience.
Transpl Immunol. 2019 06; 54:65-72.TI

Abstract

PURPOSE

For patients with end stage lung disease, lung transplantation (LT) remains the only definitive treatment option. Long term survival post LT is limited by acute and chronic allograft dysfunction. Antibodies to lung self-antigens Kα1Tubulin and collagen V (autoantibodies) have been implicated in adverse outcomes post LT. The aim of our study was to determine the prevalence of autoantibodies in pre- and post-transplant sera, evaluate the impact on post-transplant outcomes.

METHODS

In a prospective observational cohort analysis, 44 patients were enrolled who received LT between 09/01/2014 and 10/31/2015. Pre- and post-transplant sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to collagen I, collagen V, and K-alpha 1 tubulin. The outcome variables are presence of primary graft dysfunction (PGD), cumulative acute cellular rejection (ACR), treatment with pulse steroids for clinical rejection, association with DSA, and onset of Bronchiolitis Obliterans Syndrome (BOS).

RESULTS

In our cohort, 33 patients (75%) tested positive for the presence of autoantibodies. Pre-transplant autoantibodies were present in 23 patients (70%). Only a small percentage (26%) cleared these antibodies with standard immunosuppression. Some developed de novo post-transplant (n = 10). PGD was observed in 34% of our cohort, however the presence of autoantibodies did not correlate with increase in the incidence or severity of PGD. The prevalence of donor specific antibodies (DSA) in the entire cohort was 73%, with an increased prevalence of DSA noted in the autoantibody positive group (78.7% vs. 54.5%) than in the autoantibody negative group. BOS was observed in 20% of the cohort, with a median time to onset of 291 days' post-transplant. Patients with pre-transplant autoantibodies had a statistically significant decrease in BOS-free survival (p = 0.029 by log-rank test).

CONCLUSIONS

In our cohort, we observed a high prevalence of autoantibodies and DSA in lung transplant recipients. Pre-transplant autoantibodies were associated with de novo development of DSA along with a decrease in BOS-free survival. Limitations to our study include the small sample size and single center enrollment, along with limited time for follow-up.

Authors+Show Affiliations

Kaiser Permanente San Jose Medical Center, San Jose, CA, United States.St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.St. Joseph's Hospital and Medical Center, Phoenix, AZ, United States.Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States.Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, United States.Division of Pulmonary and Critical Care Medicine, University of Texas Southwestern Medical Center, Dallas, TX, United States. Electronic address: Vaidehi.kaza@utsouthwestern.edu.

Pub Type(s)

Journal Article
Observational Study
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

30794945

Citation

Rao, Usha, et al. "Prevalence of Antibodies to Lung Self-antigens (Kα1 Tubulin and Collagen V) and Donor Specific Antibodies to HLA in Lung Transplant Recipients and Implications for Lung Transplant Outcomes: Single Center Experience." Transplant Immunology, vol. 54, 2019, pp. 65-72.
Rao U, Sharma M, Mohanakumar T, et al. Prevalence of antibodies to lung self-antigens (Kα1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience. Transpl Immunol. 2019;54:65-72.
Rao, U., Sharma, M., Mohanakumar, T., Ahn, C., Gao, A., & Kaza, V. (2019). Prevalence of antibodies to lung self-antigens (Kα1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience. Transplant Immunology, 54, 65-72. https://doi.org/10.1016/j.trim.2019.02.006
Rao U, et al. Prevalence of Antibodies to Lung Self-antigens (Kα1 Tubulin and Collagen V) and Donor Specific Antibodies to HLA in Lung Transplant Recipients and Implications for Lung Transplant Outcomes: Single Center Experience. Transpl Immunol. 2019;54:65-72. PubMed PMID: 30794945.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prevalence of antibodies to lung self-antigens (Kα1 tubulin and collagen V) and donor specific antibodies to HLA in lung transplant recipients and implications for lung transplant outcomes: Single center experience. AU - Rao,Usha, AU - Sharma,Monal, AU - Mohanakumar,Thalachallour, AU - Ahn,Chul, AU - Gao,Ang, AU - Kaza,Vaidehi, Y1 - 2019/02/20/ PY - 2019/01/21/received PY - 2019/02/15/revised PY - 2019/02/17/accepted PY - 2020/06/01/pmc-release PY - 2019/2/23/pubmed PY - 2019/2/23/medline PY - 2019/2/23/entrez KW - Autoantibodies KW - Bronchiolitis obliterans syndrome KW - Donor specific antibodies KW - Lung transplant KW - Primary graft dysfunction SP - 65 EP - 72 JF - Transplant immunology JO - Transpl. Immunol. VL - 54 N2 - PURPOSE: For patients with end stage lung disease, lung transplantation (LT) remains the only definitive treatment option. Long term survival post LT is limited by acute and chronic allograft dysfunction. Antibodies to lung self-antigens Kα1Tubulin and collagen V (autoantibodies) have been implicated in adverse outcomes post LT. The aim of our study was to determine the prevalence of autoantibodies in pre- and post-transplant sera, evaluate the impact on post-transplant outcomes. METHODS: In a prospective observational cohort analysis, 44 patients were enrolled who received LT between 09/01/2014 and 10/31/2015. Pre- and post-transplant sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to collagen I, collagen V, and K-alpha 1 tubulin. The outcome variables are presence of primary graft dysfunction (PGD), cumulative acute cellular rejection (ACR), treatment with pulse steroids for clinical rejection, association with DSA, and onset of Bronchiolitis Obliterans Syndrome (BOS). RESULTS: In our cohort, 33 patients (75%) tested positive for the presence of autoantibodies. Pre-transplant autoantibodies were present in 23 patients (70%). Only a small percentage (26%) cleared these antibodies with standard immunosuppression. Some developed de novo post-transplant (n = 10). PGD was observed in 34% of our cohort, however the presence of autoantibodies did not correlate with increase in the incidence or severity of PGD. The prevalence of donor specific antibodies (DSA) in the entire cohort was 73%, with an increased prevalence of DSA noted in the autoantibody positive group (78.7% vs. 54.5%) than in the autoantibody negative group. BOS was observed in 20% of the cohort, with a median time to onset of 291 days' post-transplant. Patients with pre-transplant autoantibodies had a statistically significant decrease in BOS-free survival (p = 0.029 by log-rank test). CONCLUSIONS: In our cohort, we observed a high prevalence of autoantibodies and DSA in lung transplant recipients. Pre-transplant autoantibodies were associated with de novo development of DSA along with a decrease in BOS-free survival. Limitations to our study include the small sample size and single center enrollment, along with limited time for follow-up. SN - 1878-5492 UR - https://www.unboundmedicine.com/medline/citation/30794945/Prevalence_of_antibodies_to_lung_self_antigens__Kα1_tubulin_and_collagen_V__and_donor_specific_antibodies_to_HLA_in_lung_transplant_recipients_and_implications_for_lung_transplant_outcomes:_Single_center_experience_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0966-3274(19)30004-8 DB - PRIME DP - Unbound Medicine ER -