<<Disclaimer: Verify this information before applying it to your situation.>>
Here's some important research appearing in Lancet which suggests possible
ways to inhibit T cell activation in coeliac disease. Also, a Romanian
study finds the usefulness of seralogical CD testing in cases of mild
mucosal damage limited.
----------
Lancet. 2003 Jul 5;362(9377):30-7.
Association between innate response to gliadin and activation of pathogenic
T cells in coeliac disease.
Maiuri L, Ciacci C, Ricciardelli I, Vacca L, Raia V, Auricchio S, Picard J,
Osman M, Quaratino S, Londei M.
Institute of Child Health, University College London, London, UK.
BACKGROUND: The adaptive immune system is central to the development of
coeliac disease. Adaptive immune responses are, however, controlled by a
preceding activation of the innate immune system. We investigated whether
gliadin, a protein present in wheat flour, could activate an innate as well
as an adaptive immune response in patients with coeliac disease.
METHODS: Duodenal biopsy samples from 42 patients with untreated coeliac
disease, 37 treated patients, and 18 controls, were cultured in vitro for 3
h or 24 h, in the presence of either immunodominant gliadin epitopes (p
(alpha)-2 and p(alpha)-9) or a non-immunodominant peptide (p31-43) known to
induce small intestine damage in coeliac disease. We also incubated biopsy
samples from nine untreated and six treated patients with a non-
immunodominant peptide for 3 h, before incubation with immunodominant
gliadin epitopes. Different combinations of interleukin-15 or signal
transduction inhibitors were added to selected incubations.
FINDINGS: Only the non-immunodominant peptide induced rapid expression of
interleukin-15, CD83, cyclo-oxygenase (COX)-2, and CD25 by CD3- cells
(p=0.005 vs medium alone) and enterocyte apoptosis (p<0.0001). Only the non-
immunodominant peptide induced p38 MAP kinase activation in CD3- cells. Pre-
incubation with the non-immunodominant peptide enabled immunodominant
epitopes to induce T-cell activation (p=0.001) and enterocyte apoptosis.
Inhibition of interleukin-15 or of p38 MAP kinase controlled such activity.
INTERPRETATION: A gliadin fragment can activate the innate immune system,
affecting the in situ T-cell recognition of dominant gliadin epitopes.
Although our findings emphasise the key role of gliadin-specific T cells,
they suggest a complex pathogenic situation, and show that inhibition of
interleukin-15 or p38 MAP kinase might have the potential to control
coeliac disease.
----------
Rom J Gastroenterol. 2003 Jun;12(2):101-106.
Autoantibodies and Histogenesis of Celiac Disease.
Rostami K, Mulder CJ, Stapel S, Von Blomberg BM, Kerckhaert J, Meijer JW,
Pena SA, Heymans HS.
Department of Gastroenterology Withybush General Hospital, Fishguard Rd,
Haverfordwest, Pembrokeshire, UK, SA61 2PZ, Email:
krostami@hotmail.com.
OBJECTIVE: Autoantibodies are used as markers for celiac disease (CD)
identifying patients with mucosal lesions. The purpose of this study was to
evaluate the sensitivity and role of the autoantibodies such as IgA
antiendomysium (EMA), IgA antigliadin (AGA) and the IgA antitissue
transglutaminase (tTGA) in histogenesis of celiac disease.
METHODS: Seventy-nine cases including 30 untreated celiacs, 5 celiacs on
gluten-free diet (GFD), 41 first degree relatives and 3 non-relatives
suspected for CD were investigated. Three untreated celiacs with IgA
deficiency were excluded from this study group. IgA antibodies to tTGA were
determined by ELISA, as described before. Twelve of 41 relatives and 2
cases of non relatives suspected with positive serology underwent a small
intestinal biopsy. Results were correlated with the degrees of abnormality
of the intestinal mucosa in patients with CD. Intestinal biopsies obtained
from study population were evaluated for histological quantification.
RESULTS: Celiacs and suspected cases with positive EMA/AGA and or tTGA
showed shorter villi (p < 0.007) and/or a higher number of
intraepithelial lymphocytes (IEL) (p < 0.035). The sensitivity of
serology (EMA, AGA, tTGA) in patients with Marsh IIIc was 100%. However, in
patients with Marsh IIIa the sensitivity for EMA, AGA, and tTGA was 40%,
50% and 20% respectively.
CONCLUSIONS: The appearance of antibodies is related to the degree of
mucosal infiltration by IELs. Although tTGA, like EMA provide a highly
sensitive parameter for the detection of celiacs with severe mucosal
damage, it appears to be less sensitive (even less than AGA) in celiac
patients with milder histopathological abnormalities. However, it should be
recognized that the substantial part of the celiac population present with
these milder forms of mucosal abnormalities. Using tTGA as a single test in
screening may result in missing up to 60-70% of celiacs with mild mucosal
abnormalities. Combination with other screening tests (at least with AGA)
is essential and strongly recommended
* Please include your location in all posts about products *
|
