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

Abstract EN

Idiopathic achalasia is a disease of unknown etiology.

The loss of myenteric plexus associated with inflammatory infiltrates and autoantibodies support the hypothesis of an autoimmune mechanism.

Thirty-two patients diagnosed by high-resolution manometry with achalasia were included.

Twenty-six specimens from lower esophageal sphincter muscle were compared with 5 esophagectomy biopsies (control).

Immunohistochemical (biopsies) and flow cytometry (peripheral blood) analyses were performed.

Circulating anti-myenteric autoantibodies were evaluated by indirect immunofluorescence.

Herpes simplex virus-1 (HSV-1) infection was determined by in situ hybridization, RT-PCR, and immunohistochemistry.

Histopathological analysis showed capillaritis (51%), plexitis (23%), nerve hypertrophy (16%), venulitis (7%), and fibrosis (3%).

Achalasia tissue exhibited an increase in the expression of proteins involved in extracellular matrix turnover, apoptosis, proinflammatory and profibrogenic cytokines, and Tregs and Bregs versus controls ( P < 0.001 ).

Circulating Th22/Th17/Th2/Th1 percentage showed a significant increase versus healthy donors ( P < 0.01 ).

Type III achalasia patients exhibited the highest inflammatory response versus types I and II.

Prevalence of both anti-myenteric antibodies and HSV-1 infection in achalasia patients was 100% versus 0% in controls.

Our results suggest that achalasia is a disease with an important local and systemic inflammatory autoimmune component, associated with the presence of specific anti-myenteric autoantibodies, as well as HSV-1 infection.