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From:
Roy Jamron <[log in to unmask]>
Reply To:
Roy Jamron <[log in to unmask]>
Date:
Sat, 2 Aug 2003 16:09:26 -0500
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<<Disclaimer: Verify this information before applying it to your situation.>>

A bunch of new CD articles have been newly published.  So here's a summary
of some of the most significant:

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Scand J Gastroenterol. 2003 Jul;38(7):727-31.

Effectiveness of the sorbitol H2 breath test in detecting histological
damage among relatives of coeliacs.

Tursi A, Brandimarte G, Giorgetti GM, Inchingolo CD.

Dept. of Emergency, L. Bonomo Hospital, Andria (BA), Italy.
[log in to unmask]

BACKGROUND: Small intestinal lesions have a wide severity in coeliac
disease (CD), and early diagnosis is important in preventing neoplastic and
non-neoplastic disorders related to CD. The aim of this study was to
compare the effectiveness of the sorbitol H2 breath test (H2-BT) and
serological tests (antigliadin (AGA), antiendomysium (EMA) and anti-tissue
transglutaminase (anti-tTG)) as screening tests in the detection and
estimation of CD prevalence in 1st-degree relatives. METHODS: Screening was
performed in 111 1st-degree relatives of 37 coeliac families. Sorbitol H2-
BT, AGA, EMA and anti-tTG antibodies were used to select the candidates for
small-bowel biopsy. Relatives with abnormal serological tests and/or with
sorbitol H2-BT positivity underwent a small-bowel biopsy. Small-bowel
biopsy was also performed in relatives negative in all tests but with
clinical complaints or suspected of having CD, and intestinal lesions were
expressed according to the Marsh classification. RESULTS: CD was diagnosed
in 49/111 screened relatives (44.14%): 5 showed Marsh IIIc, 8 Marsh IIIb,
16 Marsh IIIa, 13 Marsh II and 7 Marsh I lesions. Nineteen relatives showed
the classical form of the disease, while the subclinical and silent forms
were recorded in 20 and 10, respectively. AGA, EMA and anti-tTG showed
strong positivity only in severe intestinal damage (Marsh IIIb-c lesions)
(but overall positivity was 36.73%, 38.78% and 44.89% for AGA, EMA and anti-
tTG, respectively), while sorbitol H2-BT showed strong positivity also in
patients with slight histological damage (Marsh I-IIIa) (overall positivity
was 83.67%). CONCLUSIONS: A significant proportion of coeliacs may be
missed if relatives are screened by serology only, while the efficacy of
sorbitol H2-BT in screening relatives is confirmed. This study confirms
that neither a breath test nor serology can replace intestinal biopsy,
which remains the gold standard for the diagnosis of CD.

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Scand J Gastroenterol. 2003 Jul;38(7):742-6.

Antibodies to oat prolamines (avenins) in children with coeliac disease.

Hollen E, Hogberg L, Stenhammar L, Falth-Magnusson K, Magnusson KE.

Division of Medical Microbiology, Dept. of Molecular and Clinical Medicine,
Faculty of Health Sciences, Linkoping University, Sweden. [log in to unmask]

BACKGROUND: The use of oats in a gluten-free diet for children with coeliac
disease is presently under investigation. In this study we measured the
content of antibodies to oat prolamines (avenin) in sera from coeliac
children and reference children. METHODS: Crude avenin was prepared by
extraction with ethanol and salt-solution and used as antigen in a three-
step ELISA. Sera from 81 children, including 34 children with verified
coeliac disease, were analysed for both IgA and IgG antibodies to avenin
and gliadin. Sera were also incubated with gliadin before exposure to
avenin, and vice versa, to assess a possible cross-reaction between the
species. Keyhole limpet hemocyanin (KLH) was used as a negative control.
RESULTS: Children with coeliac disease on a normal diet had significantly
higher levels of antibodies to avenin, both IgG and IgA, than reference
children (P < 0.001) and the levels correlated positively with gliadin
antibodies, especially of IgA-type (r = 0.798). Both anti-avenin and anti-
gliadin antibodies were only absorbed by the corresponding protein.
CONCLUSIONS: Children with coeliac disease have antibodies to oat proteins
at significantly higher levels than reference children. The absorption test
did not indicate a cross-reactivity between the prolamines of wheat and
oats. The method will be employed for repeated sampling of anti-avenin
antibodies during a prospective interventional study with a gluten-free
diet supplemented with oats.

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Gastroenterology. 2003 Aug;125(2):337-344.

Intestinal T-cell responses to high-molecular-weight glutenins in celiac
disease.

Molberg O, Solheim Flaete N, Jensen T, Lundin KE, Arentz-Hansen H, Anderson
OD, Kjersti Uhlen A, Sollid LM.

BACKGROUND & AIMS: The chronic, small intestinal inflammation that defines
celiac disease is initiated by a HLA-DQ2 restricted T-cell response to
ingested gluten peptides after their in vivo deamidation by tissue
transglutaminase (TG2). To date, celiac disease can only be treated by a
lifelong abstinence from foods that contain wheat, rye, or barley; better
therapeutic options are hence needed. An attractive target would be to
identify nontoxic wheat cultivars or components thereof with intact baking
qualities. Because these qualities are mainly determined by the high
molecular weight (HMW) glutenin proteins of gluten, it is critical to know
if these proteins are toxic or, more specifically, if they will trigger the
activation of T cells in the celiac lesion. METHODS: Different, highly
purified HMW glutenins were isolated from wheat cultivars or expressed as
recombinant proteins. The proteins were first tested for recognition by a
large panel of gluten-specific T-cell lines established from celiac lesions
and then applied during ex vivo challenges of celiac biopsies to allow for
a direct identification of HMW specific T cells. RESULTS: Intestinal T-cell
responses to TG2-deamidated HMW glutenins but not the corresponding native
proteins were detectable in 9 of the 22 adult and childhood celiac disease
patients tested. CONCLUSIONS: T cells within celiac lesions frequently
recognize deamidated HMW glutenin proteins. This finding questions the
possibility of implementing these proteins in novel food items destined to
be nontoxic for celiac disease patients.

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Gastroenterology. 2003 Aug;125(2):345-56.

Human small-intestinal epithelium contains functional natural killer
lymphocytes.

Leon F, Roldan E, Sanchez L, Camarero C, Bootello A, Roy G.

BACKGROUND & AIMS: CD3(-) non-T lymphocytes constitute the second most
abundant lymphoid subset in the human small-bowel epithelium, and these CD3
(-) intraepithelial lymphocytes are virtually absent in active celiac
disease. Phenotypically, they resemble natural killer cells and have been
termed natural killer-like intraepithelial lymphocytes. Because of the
limited availability of appropriate human samples, functional studies have
not yet been reported, and it is not yet clear whether these are true
natural killer cells. METHODS: We used magnetic bead-based purification and
flow cytometry to study several aspects of normal human small-bowel natural
killer-like intraepithelial lymphocytes: intracellular cytokine content
(basally and after activation); ability to lyse natural killer-sensitive
K562 target cells; and expression of perforins, Fas ligand, and other
functional markers. RESULTS: CD3(-) intraepithelial lymphocytes cultured in
interleukin-2 showed a higher lymphokine-activated killer activity than CD3
(+) intraepithelial lymphocytes (48%-83% lysis exerted by CD3(-)
intraepithelial lymphocytes at an effector-target cell ratio of 2:1 vs. 8%-
18% by CD3(+) intraepithelial lymphocytes). Perforin content correlated
with this lytic potential (75% +/- 4% in CD3(-) vs. 5% +/- 4% in CD3(+)
intraepithelial lymphocytes). Both CD3(-) and CD3(+) cells displayed a type
I cytokine profile (interferon-gamma > tumor necrosis factor-alpha >
interleukin-2; undetectable interleukin-4 and interleukin-10). In addition
to their activated phenotype, subsets of natural killer-like
intraepithelial lymphocytes expressed CD8alphaalpha and intracellular
CD3epsilon chain, showing the existence of heterogeneity within this cell
lineage. CONCLUSIONS: This is the first demonstration of functional natural
killer cells within the human gut epithelium. These cells might play an
important role in innate mucosal immunity (host defense and tumor
surveillance) and tolerance.

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Gastroenterology. 2003 Aug;125(2):429-36.

Fracture risk in people with celiac disease: A population-based cohort
study.

West J, Logan RF, Card TR, Smith C, Hubbard R.

BACKGROUND & AIMS: People with celiac disease are at risk of developing
osteoporosis, but the extent of any increased fracture risk is unclear. We
performed a population-based cohort study by using the General Practice
Research Database to quantify the fracture risk in people with celiac
disease compared with the general population. METHODS: We identified 4732
people with celiac disease, of whom 1589 were "incident" cases, and 23,620
age- and sex-matched control subjects. We used Cox regression to estimate
the hazard ratios for any fracture, hip fracture, and ulna or radius
fracture in the celiac disease cohort compared with the general population.
RESULTS: In the incident subjects with celiac disease, the mean age at
diagnosis was 44 years, and 67% were women. The overall hazard ratio for
any fracture was 1.30 (95% confidence interval, 1.16-1.46), for hip
fracture was 1.90 (95% confidence interval, 1.20-3.02), and for ulna or
radius fracture was 1.77 (95% confidence interval, 1.35-2.34). The absolute
difference in the overall fracture rate was 3.20 per 1000 person-years and
for hip fracture it was 0.97 per 1000 person-years in those older than 45
years. In 1589 incident subjects, the excess fracture risk was slightly
lower compared with the "prevalent" subjects (hazard ratio for any
fracture, 1.19 vs. 1.40, respectively). CONCLUSIONS: There were small
increases in both the absolute and relative fracture risks in people with
celiac disease; the excess risks were slightly lower in those with a more
recent diagnosis. Our data indicate that concerns regarding a markedly
increased fracture risk in celiac disease are unwarranted.

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Arq Neuropsiquiatr. 2003 Jun;61(2B):330-4. Epub 2003 Jul 28.

Free full-text: (Paste this link together on one line)
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0004-
282X2003000300002&lng=en&nrm=iso

Is the prevalence of celiac disease increased among epileptic patients?

Pratesi R, Gandolfi L, Martins RC, Tauil PL, Nobrega YK, Teixeira WA.

Medicina da Crian a e do Adolescente e Medicina Social, Faculdade de
Medicina, Universidade de Bras lia, Bras lia, DF, Brasil.

OBJECTIVE: To assess the prevalence of celiac disease (CD) among a group of
epileptic patients attending the Epilepsy Clinics of two general hospitals
in the city of Brasilia (DF), Brazil. METHOD: Serum samples were collected
from 255 epileptic patients (119 children, 136 adults) originating from
Epilepsy Clinics, and from a control group composed by 4405 individuals
(2034 children, 2371 adults) attending the Laboratory of Clinical Analysis,
for routine blood testing. The diagnosis of CD was determined by the
antiendomysium antibody (IgA-EMA) test and by small intestine biopsy.
RESULTS: two of the 255 epileptic patients (1:127) and fifteen subjects
from the control group (1:293) tested positive for the IgA-EMA assay.
CONCLUSION: the prevalence of CD was 2.3 times higher in epileptic patients
than in controls (7.84 per 1000 versus 3.41 per 1000). Although still not
statistically significant, this result is highly suggestive of an increased
prevalence of CD among epileptic patients.

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