THORACIC – Original Submission| Volume 35, ISSUE 1, P177-186, March 2023

Association Between Antibodies Against Lung Self-Antigens and Gastroesophageal Reflux in Lung Transplant Candidates

Published:February 14, 2022DOI:
      Gastroesophageal reflux (GER) and pretransplant antibodies against lung self-antigens (SAbs) collagen-V and/or k-alpha 1 tubulin are both independently associated with allograft dysfunction after lung transplantation (LTx). The role of GER in inducing lung injury and SAbs is unknown. We aimed to study the association between pre-LTx GER and SAbs. After IRB approval, we retrieved SAb assays conducted between 2015 and 2019 and collected 24 hour GER data for these patients. Patients were divided into 2 groups: no reflux (GER–) and pathologic reflux (GER+) to compare the prevalence of SAbs. Multivariate analysis was used to study the association between GER and SAbs in the whole cohort and in restrictive lung disease (RLD) and obstructive lung disease (OLD) subsets. Proximal esophageal reflux (PER) events ≥5 was considered abnormal. Patients (n = 134; 73 men) were divided into groups: GER– (54.5%, n = 73) and GER+ (45.5%, n = 61). The prevalence of GER was higher in the RLD than in the OLD subset (p < 0.001). The overall prevalence of SAbs was 53.7% (n = 72), higher in the GER+ than the GER– group (65.6% vs 43.8%, p = 0.012), but comparable between RLD and OLD subsets. Overall, SAbs were associated with GER (p = 0.012) and abnormal PER (p = 0.017). GER and abnormal PER increased the odds of SAbs in the RLD subset (OR [95% CI]: 2.825 [1.033-7.725], p = 0.040 and OR [95% CI]: 3.551 [1.271-9.925], p = 0.014, respectively) but not in the OLD subset. LTx candidates have a high prevalence of SAbs, which are significantly associated with GER and abnormal PER in patients with RLD.

      Graphical abstract



      AET (acid exposure time), BOS (bronchiolitis obliterans syndrome), Col-V (collagen type-V), ELISA (enzyme-linked immunosorbent assay), GER (gastroesophageal reflux), IQR (interquartile range), Kα1T (k-alpha 1 tubulin), LTx (lung transplantation), OLD (obstructive lung diseases), OR (odds ratio), PER (proximal esophageal reflux), RLD (restrictive lung diseases), SAbs (antibodies against lung self-antigens collagen-V and/or k-alpha 1 tubulin)
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      Linked Article

      • Commentary: Rethinking the Role of Gastroesophageal Reflux in Lung Transplant Candidates
        Seminars in Thoracic and Cardiovascular SurgeryVol. 35Issue 1
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          Chronic lung allograft dysfunction (CLAD) is the leading cause of death in the first year following lung transplantation. Gastroesophageal reflux (GER) is among one of the several risk factors for the development of CLAD.1 Early studies suggest a protective effect of anti-reflux surgery on long term transplant outcomes, especially when performed soon after lung transplantation.2–4 Accordingly, it is acknowledged that antibodies against lung self-antigens (SAbs) play an important role in determining transplant outcomes.
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