Role of interferon alpha in promoting T helper cell type 1 responses in the small intestine in coeliac disease.
Coeliac disease (CD) is caused by a CD4 T helper cell type 1 (Th1) response in the small intestinal mucosa to dietary gluten. As the major Th1 inducing cytokine, interleukin 12, is undetectable in CD gut mucosa, the mechanism by which Th1 effector cells are generated remains unknown. Interferon (IFN) alpha, a cytokine capable of promoting IFN-gamma synthesis, has been implicated in the development of Th1 mediated immune diseases. Here we report a case of CD-like enteropathy in a patient receiving IFN-alpha for chronic myeloid leukaemia. Morphological assessment of duodenal biopsies taken from the patient showed total villous atrophy, crypt cell hyperplasia, and a high number of CD3+ intraepithelial lymphocytes. Both antigliadin antibodies and antiendomysial antibodies were positive. RNA analysis revealed pronounced expression of IFN-gamma. Withdrawal of gluten from the diet resulted in a patchy improvement in intestinal morphology, normalisation of laboratory parameters, and resolution of clinical symptoms. By western blot analysis, IFN-alpha protein was seen in the duodenal mucosa from untreated CD patients but not in controls. This was associated with marked expression of IFN-gamma protein in CD mucosa. Collectively, these results suggest a role for IFN-alpha in promoting Th1 responses to gluten.
Monteleone
G
G
Division of Infection, Allergy, Inflammation, and Repair, University of Southampton School of Medicine, Southampton General Hospital, Southampton, UK.
Pender
S L
SL
Alstead
E
E
Hauer
A C
AC
Lionetti
P
P
McKenzie
C
C
MacDonald
T T
TT
D000293:Adolescent; D015153:Blotting, Western; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis / Q000276:immunology / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy*; D008875:Middle Aged; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology
D016898:Interferon-alpha; D007371:Interferon-gamma