Background: It is widely accepted that gastroesophageal reflux disease (GERD) is associated with lung damage and conditions such as pulmonary fibrosis. Circulating lung-specific self-antigens (SAgs) collagen-V (Col-V) and k-alpha-1 tubulin (K?1T) and their associated antibodies (SAbs) anti-Col-V and anti-K?1T have been associated with immune injury during chronic rejection in lung transplant recipients. We have previously demonstrated that these SAgs and SAbs are elevated in lung transplant candidates with GERD and correlate with worse outcomes after transplantation. We have also shown that these SAbs can be induced in a murine aspiration model. Thus, we hypothesized that these same SAbs might be found in the serum of patients with severe GERD and could be a marker of lung injury resulting from chronic micro-aspiration.
Methods: At our institution, blood samples from patients undergoing surgery are collected and stored under a bio-banking protocol. After IRB approval, plasma aliquots from samples taken before ARS between November 2019 and August 2022 were obtained to conduct this cross-sectional study. SAbs were quantified using an enzyme-linked immunosorbent assay (ELISA). A sample was considered positive at concentrations ?106 ng/ml for anti-Col-V and ?116 ng/ml for anti-K?1T (the cut-off was based on the mean ± 2 standard deviations from healthy controls).
Results: Samples from a total of 43 patients (34 women [79.1%]; mean age, 62±12 years; and mean BMI, 30.5±7 kg/m2) were analyzed. Twenty-eight patients (65.1%, 95% CI: 50.3-80.0%) had abnormally elevated concentrations of anti-Col-V, and 19 (44.2%, 95% CI: 28.7-59.7%) had elevated concentrations of circulating anti-K?1T. Only 13 (30.2%) patients had low (i.e., normal) concentrations of both SAbs, whereas 13 (30.2%) were positive only for one, and 17 (39.5%) were positive for both SAbs.
Conclusions: We found a high prevalence of elevated circulating humoral factors (i.e., anti-Col-V and/or anti-K?1T) in plasma samples collected from patients before ARS. This supports the evidence that GERD may be associated with pulmonary parenchymal injury from chronic micro-aspiration. Current studies are underway to determine which patients are at risk for this antibody response and how this response changes over time in patients treated with or without ARS.
