title: Esophageal achalasia: is the herpes simplex virus really innocent?
abstract: This study was designed to test the hypothesis that mononuclear cells in the myenteric plexus of patients with achalasia may be activated by herpes simplex virus type 1 (HSV-1). Strips of esophageal muscle were obtained from patients with achalasia and multiorgan transplant donors who served as control subjects. After muscle digestion, mononuclear cells were purified through a Percoll gradient and cultured in medium, either alone or containing ultraviolet-inactivated HSV-1 or poliovirus (multiplicity of infection 1:1.5). As an indicator of HSV-1-induced lymphocyte activation, we determined T-cell proliferation by means of 3H-thymidine incorporation and interferon gamma release. DNA was extracted from esophageal muscle of achalasia patients and control subjects, and used as a template for PCR analysis using primer pairs specific for HSV-1. Circulating anti-HSV-1 and HSV-2 antibodies were detected by enzyme-linked immunosorbent assay on serum samples. Fifteen patients with naive achalasia and eight control subjects were studied. The prevalence of circulating anti-HSV-1 and HSV-2 antibodies proved similar in the two groups, and no HSV-1 DNA was detected by polyermase chain reaction in the esophageal muscle samples. The proliferative index in mononuclear cells from achalasia patients stimulated with HSV-1 showed a 3.4-fold increase in comparison with control subjects (P<0.01). In addition, a 1.4-fold increase in interferon gamma release after incubation with HSV-1 was observed in cells from achalasia patients but not control subjects. The results of this study indicate that HSV-1-reactive immune cells are present in lower esophageal sphincter muscles of patients with achalasia. We hypothesize that the HSV-1-reactive lymphocytes in lower esophageal sphincter muscles of achalasia patients may contribute to damage of the neurons in the myenteric plexus and lead to the motor dysfunction.
authors.affiliation: Department of Histology, Medical and Surgical Sciences-Clinica Chirurgica 4, University of Padova School of Medicine, Padova, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Castagliuolo
authors.forename: Paola
authors.initials: P
authors.lastname: Brun
authors.forename: Mario
authors.initials: M
authors.lastname: Costantini
authors.forename: Christian
authors.initials: C
authors.lastname: Rizzetto
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Michela
authors.initials: M
authors.lastname: Costantino
authors.forename: Nicola
authors.initials: N
authors.lastname: Baldan
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zaninotto
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000032:analysis; D002478:Cells, Cultured; D004931:Esophageal Achalasia / Q000821:virology*; D004943:Esophagogastric Junction / Q000821:virology*; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008365:Manometry; D008875:Middle Aged; D018139:Simplexvirus / Q000276:immunology
chemical_list: D000914:Antibodies, Viral