Lubin F. Arevalo

432 Evidence That Achalasia Involves a Systemic Inflammatory Response

Background: To date, the exact mechanism and etiology of achlasia remains unknown. Previous studies of possible inflammatory cell mediated mechanisms have largely been histological studies. Goldblum et al demonstrated lymphocyte infiltrates around myenteric ganglion cells in achalasia esophagomyotomy specimens. Clarke et al used immunohistochemistry to classify these myenteric inflammatory cells as Th-1 lymphocytes, and noted that they remained present throughout the disease course. Kilic et al used immunohistochemistry to demonstrate increased expression of TNF-α in esophageal tissue in achalasia specimens compared to controls. Purpose: The purpose of this study was to classify the immunological infiltrate in achalasia in order to better understand the disease mechanism and etiology. We specifically sought to determine if the concentrations of inflammatory biomarkers (TNFα receptor, IL-6, IFN-γ, IL-12, and IL-4) were elevated in the sera of achalasia patients compared to healthy controls. Methods: Serum from 19 patients seen in the esophageal motility clinic with an established diagnosis of achalasia were analyzed. Exclusion criteria included previously diagnosed malignancy, autoimmune condition, immunodeficiency disorder, and current treatment with steroids or immune modulating drugs. Serum samples were also obtained from 19 age and gender matched healthy volunteers. TNF-α receptor, IL-6, IL-10, IFN-γ, IL-12, and IL-4 levels were assayed via SearchLight multiplex ELISA (Pierce Endogen). ArrayVisionTM software was used to calculate the concentrations. Data from the achalasia patients and healthy volunteers were analyzed blindly using a two tailed Mann-Whitney test. Results: The characteristics of the patient group (mean age 62, 50% female) and the volunteer group (mean age 60, 45% female) were similar. There were statistically significant elevations in levels of IL-12 (p= .031) and TNF-α receptor (p=.026) in the achalasia group compared to the controls. There was also a trend toward elevations in IL-6 levels in the achalasia group, but this difference did not reach statistical significance (p=.053). The other biomarkers were either undetectable in both groups or did not show any significant differences. Conclusion: Our study supports the theory that achalasia is an immunologically mediated process that involves both macrophage and Th1 cytotoxic Tcells. These results are consistent with prior histological studies that demonstrated a persistent immune response in achalasia that does not resolve over time. Our study suggests that the inflammatory response is systemic and not limited to local esophageal tissue.