Abstract
Gastroesophageal reflux disease (GERD) has been associated with aspiration-induced pulmonary injury; however, good clinical or laboratory markers are not available. Increased serum levels of exosomes containing normally sequestered primary lung self-antigens (collagen-V, Kα1-tubulin) have been associated with lung injury in the lung transplant population. The aim of this pilot study was to assess the prevalence of exosomes containing collagen-V and/or Kα1-tubulin in patients with severe GERD.
Methods
After IRB approval, the institutional biobank database was queried to identify non-lung transplant patients who underwent primary anti-reflux surgery (ARS) from 2019 to 2020. Serum samples were retrieved from the repository. Exosome pellets were isolated using the Invitrogen® kit using the manufacturer’s protocol. The size of exosomes in the pellet was confirmed using NanoSight. Western blot of the exosomes was used to isolate and quantify collagen-V and Kα1-tubulin, using CD-9 as the standard. A ratio > 1 was considered abnormal.
Results
Ten patients (6 females) with a median (IQR) age of 53 (42, 63) years were included in this study. All patients had symptomatic GERD as an indication for ARS. Five patients (50%) had exosomes containing abnormal levels of collagen-V and/or Kα1-tubulin (Figure 1). There was a mean 2.9- and 8.2-fold increase in collagen-V and Kα1-tubulin, respectively.
Conclusion
Humoral factors associated with lung injury are highly prevalent in patients undergoing elective ARS for GERD. This suggests that detection of exosomes containing lung self-antigens collagen-V and Kα1-tubulin could be useful as a biomarker of GERD-induced lung injury.
The impact of cytochrome P450 3A5 genotype on early tacrolimus metabolism and clinical outcomes in lung transplant recipients
