Esophageal achalasia: is the herpes simplex virus really innocent?
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.
Castagliuolo
Ignazio
I
Department of Histology, Medical and Surgical Sciences-Clinica Chirurgica 4, University of Padova School of Medicine, Padova, Italy.
Brun
Paola
P
Costantini
Mario
M
Rizzetto
Christian
C
Palù
Giorgio
G
Costantino
Michela
M
Baldan
Nicola
N
Zaninotto
Giovanni
G
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
D000914:Antibodies, Viral