Introduction: Gastroesophageal reflux disease (GERD) is common following lung transplantation and has been associated with bronchiolitis obliterans syndrome (BOS). Data from our center suggests that lung transplant recipients with GERD who undergo fundoplication have a lower incidence of BOS and prolonged survival. The current study investigates the role of cell-mediated immunity in GERD and BOS following lung transplantation. Methods: Whole blood from 19 lung transplant recipients was stimulated with phytohemagglutinin for 18 hours. CD4+ cells were isolated using magnetic beads and intracellular ATP (iATP) levels were measured as a surrogate for cell-mediated reactivity using a luminometer (ImmuKnow, Cylex, Inc). All patients underwent esophageal pH testing. Of those with pH-confirmed GERD (n = 12), 7 underwent fundoplication. Results: Mean iATP levels were higher for patients with GERD (n = 5) when compared to patients without GERD (n = 14 including those who had undergone fundoplication) (604.4 ± 278.2 vs. 440.1 ± 197.6, p=0.08). When sensitized patients (having anti-HLA antibodies detected by flow cytometry) were excluded from analysis, iATP levels were significantly higher for patients with BOS (n = 6) than for those without BOS (n = 6) (508.0 ± 221.0 vs. 332.5 ± 80.6, p=0.05). Non-sensitized patients with either GERD or BOS (n = 7) exhibited significantly higher iATP levels than those without GERD who were BOS-free (n = 5) (496.7 ± 203.9 vs. 313.2 ± 72.9, p=0.04). Conclusions: Lung transplant recipients with pH-confirmed GERD or BOS exhibit upregulated cell-mediated reactivity. This provides the first evidence of an alloimmune cellular mechanism for GERD-associated BOS and supports the hypothesis that GERD may augment alloimmune injury.
