Serum anti-enteric neuronal antibodies in patients with achalasia and their association with clinical profiles
TL;DR
Serum AENA is prevalent in AC and correlates with disease severity in a dose-dependent manner and with early treatment response, potentially identifying patients with more severe disease characteristics and poorer outcomes.
Abstract
Background
Immune-mediated mechanisms are implicated in the pathogenesis of achalasia of cardia (AC), which is characterized by inflammation-driven degeneration of myenteric neurons. Circulating autoantibodies targeting the enteric nervous system may serve as potential biomarkers reflecting this underlying neurodegeneration. However, the clinical significance of anti-enteric neuronal antibodies (AENAs) in disease progression and treatment outcomes remains unexplored.
Aim
To evaluate the prevalence of AENA in AC and its correlation with clinical characteristics and treatment outcomes.
Methods
This prospective cohort study included 97 patients with AC diagnosed according to the Chicago Classification version 4.0 and 98 age- and sex-matched healthy subjects (HS). Indirect immunofluorescence was used to detect AENA and antinuclear antibodies. Multivariable linear regression analyses were performed to explore associations between AENA intensity and clinical parameters in patients with AC.
Results
The AENA-positive rate was significantly higher in patients with AC than HS (60.8% vs 25.5%, P < 0.001). AENA-positive patients had higher endoscopic CARS (contents, anatomy, resistance, and stasis) than AENA-negative patients (5.0 vs 4.0, P = 0.045), whereas Eckardt scores and manometric parameters did not differ between groups. Multivariable regression identified strong AENA positivity as independently associated with higher CARS (β = 0.95, 95% confidence interval: 0.37-1.53, P = 0.002), demonstrating a dose-response relationship (P for trend = 0.005). Patients with strong AENA intensity also exhibited greater barium column width and higher integrated relaxation pressure than those with moderate intensity. After peroral endoscopic myotomy and overlap weighting, AENA-positive patients had worse Eckardt scores at 1- and 6-month follow-up than AENA-negative patients (P = 0.031 and P = 0.005, respectively).
Conclusion
Serum AENA is prevalent in AC and correlates with disease severity in a dose-dependent manner and with early treatment response, potentially identifying patients with more severe disease characteristics and poorer outcomes.