Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study

Area of Science:

• Gastroenterology
• Immunology
• Virology

Background:

• Idiopathic achalasia pathogenesis remains unclear, though autoimmune mechanisms are hypothesized.
• Evidence includes myenteric plexus loss, inflammation, and autoantibodies in achalasia patients.

Purpose of the Study:

• To investigate the autoimmune and infectious components in achalasia.
• To identify specific autoantibodies and the role of herpes simplex virus-1 (HSV-1) in achalasia.

Main Methods:

• Compared lower esophageal sphincter muscle biopsies from 32 achalasia patients with 5 control samples.
• Utilized immunohistochemistry, flow cytometry, indirect immunofluorescence, in situ hybridization, and RT-PCR.
• Assessed circulating T-cell subsets and anti-myenteric autoantibodies, alongside HSV-1 detection.

Main Results:

• Achalasia tissues showed increased extracellular matrix turnover, apoptosis, inflammatory cytokines, and regulatory T and B cells (Tregs/Bregs).
• Patients exhibited elevated circulating Th22/Th17/Th2/Th1 cells and 100% prevalence of anti-myenteric antibodies and HSV-1 infection.
• Type III achalasia displayed the most significant inflammatory response.

Conclusions:

• Achalasia presents with significant local and systemic autoimmune inflammation.
• The findings strongly associate achalasia with anti-myenteric autoantibodies and HSV-1 infection.
• These factors likely contribute to the pathogenesis of achalasia.