title: Achalasia--An Autoimmune Inflammatory Disease: A Cross-Sectional Study.
abstract: 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.
authors.affiliation: Department of Immunology and Rheumatology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: J
authors.initials: J
authors.lastname: Furuzawa-Carballeda
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: D
authors.initials: D
authors.lastname: Aguilar-León
authors.affiliation: Department of Pathology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Gamboa-Domínguez
authors.affiliation: Department of Gastroenterology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: M A
authors.initials: MA
authors.lastname: Valdovinos
authors.affiliation: Department of Immunology and Rheumatology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: C
authors.initials: C
authors.lastname: Nuñez-Álvarez
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: L A
authors.initials: LA
authors.lastname: Martín-del-Campo
authors.affiliation: Department of Immunology and Rheumatology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: A B
authors.initials: AB
authors.lastname: Enríquez
authors.affiliation: Department of Gastroenterology, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: E
authors.initials: E
authors.lastname: Coss-Adame
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: A E
authors.initials: AE
authors.lastname: Svarch
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Flores-Nájera
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: A
authors.initials: A
authors.lastname: Villa-Baños
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: J C
authors.initials: JC
authors.lastname: Ceballos
authors.affiliation: Department of Experimental Surgery, National Institute of Medical Sciences and Nutrition, Vasco de Quiroga No. 15, Colonia Sección XVI, 14000 Mexico City, DF, Mexico.
authors.forename: G
authors.initials: G
authors.lastname: Torres-Villalobos
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004931:Esophageal Achalasia / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect / Q000379:methods; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007249:Inflammation / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D009197:Myenteric Plexus / Q000276:immunology / Q000473:pathology / Q000821:virology
chemical_list: D001323:Autoantibodies