Skip to main content
Log in

Anti-Myenteric Neuronal Antibodies in Patients with Achalasia (A Prospective Study)

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Achalasia is a motility disorder of theesophagus characterized by the loss of inhibitoryneurons in the distal esophagus. Although idiopathic innature, autoimmune mechanisms have been proposed, and we set out to determine the presence of myentericneuronal antibodies. We prospectively studied 18patients with well-characterized achalasia (by clinical,x-ray, and manometric evidence), nine withgastroesophageal reflux disease, and analyzed the sera from 22disease-free controls. Using double-label, indirectimmunofluorescence techniques, rat esophageal andintestinal sections were double-labeled with sera(dilutions of 1:50 to 1:400) from the three groups andwith neurofilament antibody to localize neurons. Sevenof 18 achalasia patients had sera that stained themajority of neurons within plexi in the esophageal and intestinal sections, including both NADPHdiaphorase (nitric oxide synthase) -positiveand-negative neurons. None of the gastroesophagealreflux patients or the controls showed staining.Neuronal antibodies in achalasia provide an attractive hypothesisto explain this diffuse, possibly immune-based disorder.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Edoardo Savarino, Shobna Bhatia, … C. Prakash Gyawali

REFERENCES

  1. Richter JE: Motility disorders of the esophagus. In Textbook of Gastroenterology, 2nd ed. T Yamada (ed). Philadelphia, JB Lippincott, 1995, pp 1174–1213

    Google Scholar 

  2. Reynolds JC, Parkman HP: Achalasia. Gastroenterol Clin North Am 18:223–255, 1989

    Google Scholar 

  3. Csendes A, Smok G, Braghetto I, Ramirez C, Velasco N, Henriquez A: Gastroesophageal sphincter pressure and histological changes in distal esophagus in patients with achalasia of the esophagus. Dig Dis Sci 30:941–945, 1985

    Google Scholar 

  4. Misiewicz JJ, Waller SL, Anthony PP, Gummer JWP: Achalasia of the cardia: Pharmacology and histopathology of isolated cardiac sphincteric muscle from patient with and without achalasia. Q J Med 194:17–30, 1969

    Google Scholar 

  5. Cassella RR, Brown AL, Sayre GP, Ellis FH: Achalasia of the esophagus: Pathologic and etiologic considerations. Ann Surg 160:474, 1964

    Google Scholar 

  6. Bettarello A, Pinott HW: Oesophageal involvement in Chagas' disease. Clin Gastroenterol 5:103, 1976

    Google Scholar 

  7. Zimmerman FH, Rosenweig NS: Achalasia in a father and son. am J Gastroenterol 79:506–508, 1984

    Google Scholar 

  8. Qualman SJ, Haupt HM, Yang P, Hamilton SR: Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson's disease. Gastroenterology 87:848–856, 1984

    Google Scholar 

  9. Smith B: The neurological lesion in achalasia of the cardia. Cut 11:388–391, 1970

    Google Scholar 

  10. Jones DB, Mayberry JF, Rhodes J, Manro J: Preliminary report of an association between measles virus and achalasia. J Clin Pathol 36:655–657, 1983

    Google Scholar 

  11. Robertson CS, Martin BAB, Atkinson M: Varicella-zoster virus DNA in the oesophageal myenteric plexus in achalasia. Gut 34:299–302, 1993

    Google Scholar 

  12. Wong RKH, Maydonovitch CL, Metz SJ, Baker JR: Significant DQ11 association in achalasia. Dig Dis Sci 34:349–352, 1989

    Google Scholar 

  13. Singaram C, Sweet MA, Belcaster GM, Hefle SL, Kalloo AN, Pasricha J: A novel autoantibody exists in patients with esophageal achalasia. Gastroenterology 106:A566, 1994

    Google Scholar 

  14. Howe S, Eaker EY, Sallustio JE, Peebles C, Tan EM, Williams RC Jr: Antimyenteric neuronal antibodies in scleroderma. J Clin Invest 1994:761–770, 1994

    Google Scholar 

  15. Lennon VA, Sas DF, Busk MF, Scheithauer B, Malagelada J-R, Camilleri M, Miller LJ: Enteric neuronal autoantibodies in pseudo-obstruction with small-cell lung carcinoma. Gastroenterology 100:137–142, 1991

    Google Scholar 

  16. Eaker EY, Sallustio JE: The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine. Gastroenterology 107:666–674, 1994

    Google Scholar 

  17. Nichols K, Staines W, Krantis A: Nitric Oxide Synthase distribution in the rat intestine: A histochemical analysis. Gastroenterology 105:1651–1661, 1993

    Google Scholar 

  18. Aggestrup S, Uddman R, Sundler F, Fahrenkrug J, Hakanson R, Sorensen HR, Hambraeus G: Lack of vasoactive intestinal polypeptide nerves in esophageal achalasia. Gastroenterology 84:924–927, 1983

    Google Scholar 

  19. Aggestrup S, Uddman R, Jensen SL, Sundler F, de Muckadell OS, Holst JJ, Hoakanson R, Ekman R, Sorensen HR: Regulatory peptides in the lower esophageal sphincter of man. Regul Pept 10:167, 1985

    Google Scholar 

  20. Mearin F, Moruelle M, Guarner F, Salas A, Riveros-Moreno V, Moncada S, Malagelada JR: Patients with achalasia lack nitric oxide synthase in the gastro-esophageal junction. Eur J Clin Invest 23:724–728, 1993

    Google Scholar 

  21. Dodds WJ, Dent J, Hogan WJ, Patel GK, Toouli J, Arndofer RC: Paradoxical lower esophageal sphincter contraction induced by cholecystokinin-octapeptide in patients with achalasia. Gastroenterology 80:327–333, 1981

    Google Scholar 

  22. Cassella RR, Ellis FH Jr, Brown AL Jr: Fine-structural changes in achalasia of the esophagus. I. Vagus nerves. Am J Pathol 46:279–288, 1965

    Google Scholar 

  23. Atkinson M, Ogilvie AL, Robertson CS, Smart HL: Vagal function in achalasia of the cardia. Q J Med 240:297, 1987

    Google Scholar 

  24. Higgs B, Kerr FWL, Ellis FH Jr: The experimental production of esophageal achalasia by electrolytic lesions in the medulla. J Thorac Cardiovasc Surg 50:613–625, 1965

    Google Scholar 

  25. Eckardt VF, Stenner F, Liewn H, Roder R, Koop H, Bernhard G: Autonomic dysfunction in patients with achalasia. Neurogastroenterol Motil 7:55–61, 1995

    Google Scholar 

  26. Cohen S: Clinical aspects of autonomic nerve dysfunction of the gut. Scand J Gastroenterol 71:125–131, 1982

    Google Scholar 

  27. Gabella G: Innervation of the gastrointestinal tract. Int Rev Cytol 59:130–187, 1979

    Google Scholar 

  28. Caras SD, Brashear HR, McCallum RW, Smith TK: Effect of human antineuronal antibodies on the ascending excitatory reflex in the isolated guinea-pig ileum: An enteric motor disorder? Am J Gastroenterol 90:1631, 1995

    Google Scholar 

  29. Treacy WL, Baggenstoss AH, Slocumb CH, Code CF: Scleroderma of the esophagus, a correlation of histologic and physiologic findings. Ann Intern Med 59:351–356, 1963

    Google Scholar 

Download references

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Verne, G.N., Sallustio, J.E. & Eaker, E.Y. Anti-Myenteric Neuronal Antibodies in Patients with Achalasia (A Prospective Study). Dig Dis Sci 42, 307–313 (1997). https://doi.org/10.1023/A:1018857617115

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1018857617115

Navigation