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Observational Study
. 2019 Jun:54:65-72.
doi: 10.1016/j.trim.2019.02.006. Epub 2019 Feb 20.

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

Usha Rao  1 , Monal Sharma  2 , Thalachallour Mohanakumar  2 , Chul Ahn  3 , Ang Gao  3 , Vaidehi Kaza  4
Affiliations
Observational Study

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

Usha Rao et al. Transpl Immunol. 2019 Jun.

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.

Keywords: Autoantibodies; Bronchiolitis obliterans syndrome; Donor specific antibodies; Lung transplant; Primary graft dysfunction.

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Conflict of interest statement

Competing Interest Statement: Authors have no competing interests to declare

Figures

Figure 1.
Figure 1.
Enrollment and presence of autoantibodies
Figure 2a.
Figure 2a.
Association of autoantibodies with DSA
Figure 2b.
Figure 2b.
Autoantibody concentration and DSA
Figure 3a.
Figure 3a.
Correlation of autoantibodies and development of BOS
Figure 3b.
Figure 3b.
Pre-existing autoantibodies decrease BOS free survival of lung transplant recipients.
Figure 4.
Figure 4.
Presence of autoantibodies and DSA and survival rate of Lung transplant recipients
See this image and copyright information in PMC

References

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