title: Enhanced reactivity of peripheral blood immune cells to HSV-1 in primary achalasia.
abstract: OBJECTIVE
  Achalasia is the best characterized oesophageal motor disorder but the etiology is unknown. The pathology is characterized by a decrease in nitric oxide-producing neurons and the presence of an activated T-cell inflammatory infiltrate in the myenteric plexus that are reactive to HSV-1 viral antigens. These findings are not present in normal controls. The current study compared the reactivity of peripheral blood mononuclear cells (PBMCs) between patients with primary achalasia and normal controls to determine if PBMCs of patients exhibit a similar heightened reactivity to the virus.
  
  
  METHODS
  Whole blood culture experiments were conducted with heparinized peripheral venous blood obtained from 151 patients with primary achalasia and 118 healthy controls. Whole blood was cultured in the presence of ultraviolet inactivated HSV-1 or conditioned cell culture media. Reactivity of mononuclear cells to viral antigens was quantified by measuring expression of the cytokine gene interferon-gamma using Taqman real-time polymerase chain reaction. Data are expressed as cytokine fold change corresponding to ratio of interferon-gamma messenger RNA copies produced in antigen stimulated versus unstimulated cells.
  
  
  RESULTS
  The interferon-gamma fold change was higher in cases 61.33 (20.54-217.00) than controls 49.67 (10.05-157.05). Mean fold change difference between cases and controls was 1.66 times (95% confidence interval 1.17-2.34, p = 0.004).
  
  
  CONCLUSIONS
  These results indicate that the PBMCs of patients with primary achalasia show an enhanced immune response to HSV-1 antigens. The data suggest that there is persistent stimulation of immune cells by herpes simplex virus type 1 (HSV-1) or HSV-1 like antigen moieties.
authors.affiliation: Department of Gastroenterology, Royal Victoria Hospital, Belfast, Northern Ireland, UK.
authors.forename: Kar W
authors.initials: KW
authors.lastname: Lau
authors.forename: Conal
authors.initials: C
authors.lastname: McCaughey
authors.forename: Peter V
authors.initials: PV
authors.lastname: Coyle
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Murray
authors.forename: Brian T
authors.initials: BT
authors.lastname: Johnston
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004931:Esophageal Achalasia / Q000276:immunology* / Q000821:virology*; D005260:Female; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008875:Middle Aged