Gluten_Toxicity

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time will come when medicine will organize itself into an
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doctors and deny equal privileges to others will constitute
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Signer of the Declaration of Independence

Toxicity of Wheat Gluten

High-dose glycine added to olanzapine and risperidone for the treatment of
schizophrenia.
1: Acta Psychiatr Scand. 2006 Feb;113(2):82-90.
PMID: 16423158

Full Citation: "OBJECTIVE: Schizophrenia affects roughly 1% of the population and is considered one of
the top 10 causes of disability worldwide. Given the immense cost to society, successful treatment options
are imperative. Based on initial findings, gluten withdrawal may serve as a safe and economical alternative
for the reduction of symptoms in a subset of patients. METHOD: A review of the literature relevant to the
association between schizophrenia and celiac disease (gluten intolerance) was conducted. RESULTS: A
drastic reduction, if not full remission, of schizophrenic symptoms after initiation of gluten
withdrawal has been noted in a variety of studies. However, this occurs only in a subset of
schizophrenic patients. CONCLUSION: Large-scale epidemiological studies and clinical trials are needed
to confirm the association between gluten and schizophrenia, and address the underlying mechanisms by
which this association occurs."

Gluten withdrawal shows great promise in the treatment of schizophrenia.

Neurological Toxicity

Neurologic presentation of celiac disease.
1: Gastroenterology. 2005 Apr;128(4 Suppl 1):S92-7.
PMID: 15825133

Full Citation: "Celiac disease (CD) long has been associated with neurologic and psychiatric disorders
including cerebellar ataxia, peripheral neuropathy, epilepsy, dementia, and depression. Earlier reports mainly
have documented the involvement of the nervous system as a complication of prediagnosed CD. However,
more recent studies have emphasized that a wider spectrum of neurologic syndromes may be the
presenting extraintestinal manifestation of gluten sensitivity with or without intestinal pathology. These
include migraine, encephalopathy, chorea, brain stem dysfunction, myelopathy, mononeuritis multiplex,
Guillain-Barre-like syndrome, and neuropathy with positive antiganglioside antibodies. The association
between most neurologic syndromes described and gluten sensitivity remains to be confirmed by larger
epidemiologic studies. It further has been suggested that gluten sensitivity (as evidenced by high antigliadin
antibodies) is a common cause of neurologic syndromes (notably cerebellar ataxia) of otherwise unknown
cause. Additional studies showed high prevalence of gluten sensitivity in genetic neurodegenerative disorders
such as hereditary spinocerebellar ataxia and Huntington's disease. It remains unclear whether gluten
sensitivity contributes to the pathogenesis of these disorders or whether it represents an epiphenomenon.
Studies of gluten-free diet in patients with gluten sensitivity and neurologic syndromes have shown variable
results. Diet trials also have been inconclusive in autism and schizophrenia, 2 diseases in which sensitivity to
dietary gluten has been implicated. Further studies clearly are needed to assess the efficacy of gluten-free diet
and to address the underlying mechanisms of nervous system pathology in gluten sensitivity."

A large number of neurologic syndromes may result from gluten intolerance.

Is schizophrenia rare if grain is rare?
1: Biol Psychiatry. 1984 Mar;19(3):385-99.
PMID: 6609726

Full Citation: "If, as hypothesized, neuroactive peptides from grain glutens are the major agents evoking
schizophrenia in those with the genotype(s), it should be rare if grain is rare. To test this, we analyzed the
results of our clinical examinations (e.g., kuru) and observations of anthropologists on peoples consuming
little or no grain. Only two overtly insane chronic schizophrenics were found among over 65,000 examined
or closely observed adults in remote regions of Papua New Guinea (PNG, 1950-1967) and Malaita ,
Solomon Islands (1980-1981), and on Yap , Micronesia (1947-1948). In preneuroleptic Europe over 130
would have been expected. When these peoples became partially westernized and consumed wheat, barley
beer, and rice, the prevalence reached European levels. Our findings agree with previous epidemiologic
and experimental results indicating that grain glutens are harmful to schizophrenics."

Schizophrenia prevalence is correlated with gluten grain consumption.

Wheat gluten as a pathogenic factor in schizophrenia.
1: Science. 1976 Jan 30;191(4225):401-2. PMID: 1246624

Full Citation: "Schizophrenics maintained on a cereal grain-free and milk-free diet and receiving optimal
treatment with neuropleptics showed an interruption or reversal of their therapeutic progress during a
period of "blind" wheat gluten challenge. The exacerbation of the disease process was not due to
variations in neuroleptic doses. After termination of the gluten challenge, the course of improvement was
reinstated. The observed effects seemed to be due to a primary schizophrenia-promoting effect of wheat
gluten."

Gliadin causes intestinal permeability in both celiac and non-celiac intestinal
mucosa.

Gastrointestinal Toxicity

Full Citation: "OBJECTIVE: Little is known about the interaction of gliadin with intestinal epithelial
cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We
investigated whether gliadin has any immediate effect on zonulin release and signaling. MATERIAL
AND METHODS: Both ex vivo human small intestines and intestinal cell monolayers were exposed to
gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence
and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula
occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction
occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR).
RESULTS: When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin
in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell
cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer
permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting
zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission
expressed a sustained luminal zonulin release and increase in intestinal permeability that was
blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited,
transient zonulin release which was paralleled by an increase in intestinal permeability that never
reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure
caused down-regulation of both ZO-1 and occludin gene expression. CONCLUSIONS: Based on our
results, we concluded that gliadin activates zonulin signaling irrespective of the genetic
expression of autoimmunity, leading to increased intestinal permeability to macromolecules."

Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac
intestinal mucosa and intestinal cell lines.
1: Scand J Gastroenterol. 2006 Apr;41(4):408-19.
PMID: 16635908

Wheat lectin may be responsible for contributing to intestinal disease.

Full Citation: "Although a variety of plant lectins are consumed as part of the normal human diet
and are capable of binding to intestinal cell surfaces in vitro, little information exists on their effects
on intact intestine. We have studied the acute effects of intraluminal administration of wheat germ
agglutinin and concanavalin A in normal rats. Both lectins caused increased shedding of brush
border membrane and, at higher concentrations, reduction in surface area, acceleration of cell loss,
and shortening of villi. These changes were prevented by simultaneous administration of the
appropriate sugar to inhibit binding, indicating that the effects were related to binding to
carbohydrate residues of intestinal cells. Similar changes of brush borders were found after
intraluminal administration of antiserum to sucrase-isomaltase, a surface protein of the brush border
membrane, suggesting that the lectin effects resulted from cell surface receptor-lectin interaction
rather than a primary intracellular effect. Our results suggest that dietary lectins may be in part
responsible for normal turnover of brush border membrane, and support, in addition, the
possibility that certain intestinal diseases such as celiac sprue may be the consequence of
increased levels of lectin receptor allowing a dietary lectin to exert a toxic effect."
"

In vivo responses of rat intestinal epithelium to intraluminal dietary lectins.
1: Gastroenterology. 1982 May;82(5 Pt 1):838-48.
PMID: 6895878

Wheat bread consumption is correlated with increased risk for kidney cancer.

Cancer

Full Citation: "Although nutrition and diet have been related to renal cell carcinoma (RCC), the role
of specific foods or nutrients on this cancer is still controversial. We evaluated the relation between a
wide range of foods and the risk of RCC in an Italian case-control study including 767 patients (494
men and 273 women) younger than 79 years with incident, histologically confirmed RCC, and 1,534
controls (988 men and 546 women) admitted to the same hospitals as cases for a wide spectrum of
acute, non-neoplastic conditions, not related to long term diet modifications. A validated and
reproducible food frequency questionnaire, including 78 foods and beverages, plus a separate
section on alcohol drinking, was used to assess patients' dietary habits 2 years before diagnosis or
hospital admission. Multivariate odds ratios (OR) were obtained after allowance for energy intake
and other major confounding factors. A significant direct trend in risk was found for bread (OR = 1.94
for the highest versus the lowest intake quintile), and a modest excess of risk was observed for pasta
and rice (OR = 1.29), and milk and yoghurt (OR = 1.27). Poultry (OR = 0.74), processed meat (OR =
0.64) and vegetables (OR = 0.65) were inversely associated with RCC risk. No relation was found for
coffee and tea, soups, eggs, red meat, fish, cheese, pulses, potatoes, fruits, desserts and sugars.
The results of this study provide further indications on dietary correlates of RCC, and in
particular indicate that a diet rich in refined cereals and poor in vegetables may have an
unfavorable role on RCC."

Food groups and renal cell carcinoma: a case-control study from Italy.
1: Int J Cancer. 2007 Feb 1;120(3):681-5.Click here to read
PMID: 17058282

Celiac disease is significantly higher in those diagnosed with Sjogren's syndrome.

Sjogren's syndrome

Full Citation: "Recent studies report that in patients with Sjögren's syndrome (SS), concomitant
coeliac disease (CD) is more frequent than in the average healthy population, with dominance of the
latent/silent form. We further investigated this to characterise the clinical and immunolaboratory
features of SS patients with CD. One hundred and eleven patients with SS were involved in the
study. After detailed history, blood samples were taken for antibodies to gliadin, endomysium, and
tissue transglutaminase. Of them, six had positive serology for CD and underwent jejunoscopy and
small bowel biopsy to confirm the diagnosis of CD. In five patients, the diagnosis was established
histologically. The frequency of CD in the SS population was significantly higher than in the
non-SS European population (4.5:100 vs 4.5-5.5:1,000). Laboratory findings in these patients
showed significantly higher erythrocyte sedimentation rates and IgG, IgA, and IgM levels. On
the basis of these findings, we recommend screening, follow-up, and regular gastrointestinal care of
SS patients to identify CD cases and help them to avoid severe malnutrition and intestinal
malignancies."

Coeliac disease in Sjögren's syndrome--a study of 111 Hungarian patients.
1: Rheumatol Int. 2004 Sep;24(5):278-82. Epub 2003 Sep 17.Click here to read
PMID: 13680146

Full Citation: "OBJECTIVE: Many autoimmune diseases occur concomitantly with celiac disease. We
investigated prospectively the occurrence of celiac disease and small-bowel mucosal inflammation in
patients with primary Sjögren's syndrome. METHODS: A total of 34 patients with primary Sjögren's
syndrome and 28 controls underwent small bowel biopsy. Villous morphology, jejunal intraepithelial
lymphocytes, and mucosal HLA-DR were evaluated and DQA and DQB alleles, serum
antiendomysial, and antigliadin antibodies were examined. RESULTS: Five (14.7%) of 34 Sjögren's
syndrome patients were found to have celiac disease. The density of jejunal intraepithelial
gammadelta+ T cells was increased in all celiac and in four nonceliac patients. All celiac patients,
69% of nonceliac Sjögren's syndrome patients, and 11% of control subjects showed enhanced
HLA-DR expression (p < 0.001). HLA DQ2 was present in 19 (56%) patients with Sjögren's
syndrome, including all five with celiac disease. CONCLUSIONS: The findings show a close
association between Sjögren's syndrome and celiac disease. Even among nonceliac patients
with primary Sjögren's syndrome, an ongoing inflammation is often present in the small bowel
mucosa."

Celiac disease and markers of celiac disease latency in patients with primary
Sjögren's syndrome.
1: Am J Gastroenterol. 1999 Apr;94(4):1042-6.
PMID: 10201480

Sjogren's syndrome is associated with ongoing inflammation in the small bowel
mucosa, not unlike what occurs in Celiac disease, indicating the therapeutic
benefits of a wheat-free diet.

Gluten sensivity may not be detectable with conventional light microscopy.

Full Citation: "BACKGROUND: Early pathogenetic events of gluten intolerance may be overlooked
in patients with serologic markers of celiac disease and normal intestinal mucosa by both
conventional histology and immunohistochemistry. AIMS: To investigate if a submicroscopical
damage of the absorptive cell surface was associated with developing gluten sensitivity. PATIENTS
AND METHODS: Duodenal biopsies of seven subjects with positive anti-endomysial antibodies and
normal histology underwent ultrastructural evaluation of the epithelial surface by means of both
scanning and transmission electron microscopy. Specimens of intestinal mucosa of 14 children with
non-celiac conditions were used as controls. RESULTS: In four patients, electron microscopy
revealed alterations of the enterocyte brush border with a significant reduction of the height of
microvilli. After several months, three of them had a second biopsy that eventually showed
histological modifications suggestive of celiac disease. In the other three patients, no significant
alteration of enterocyte ultrastructure was observed. One of them, rebiopsied after 12 months, still
showed a normal duodenal histology. CONCLUSIONS: Gluten sensitivity can be associated with
'minimal' mucosal changes not detectable with conventional light microscopy. Such lesions,
which primarily involve microvillous structure, may imply a reduction of intestinal absorptive
surface already in the latent stage of the disease."
"

Gluten sensitivity and 'normal' histology: is the intestinal mucosa really
normal?
1: Dig Liver Dis. 2003 Nov;35(11):768-73.
PMID: 14674666

Read the article: "The Dark Side
of Wheat," by Sayer Ji, to learn
more about the problem.

Palmoplantar pustulosis and gluten sensitivity: a study of serum antibodies against gliadin
and tissue transglutaminase, the duodenal mucosa and effects of gluten-free diet.
1: Br J Dermatol. 2007 Apr;156(4):659-66. Epub 2007 Jan 30. PMID: 17263812

Full Citation: "BACKGROUND: Palmoplantar pustulosis (PPP) is a chronic inflammatory disease affecting
mainly smoking women. Some patients also have psoriasis. A subgroup of patients with psoriasis has been
shown to have silent gluten sensitivity with relevance for their psoriasis. Nothing is known about gluten
sensitivity in PPP. OBJECTIVES: To find out whether any patients with PPP are gluten-sensitive and whether
this might be relevant for the PPP activity. PATIENTS AND METHODS: One hundred and twenty-three
patients (113 women) with PPP participated. Screening for IgA antibodies against gliadin and tissue
transglutaminase (tTG) was performed, the duodenal mucosa in patients with and without these antibodies
was studied and the effect of a gluten-free diet (GFD) was followed up. RESULTS: Twenty-two patients (18%)
had IgA antibodies against gliadin and nine of 94 (10%) against tTG. Twelve patients with antibodies and 11
without underwent gastro-duodenoscopy. Four displayed villous atrophy, whereas all other specimens were
judged as essentially normal at routine staining. However, with immunohistochemistry, the numbers of CD3+
and CD8+ lymphocytes in the epithelium were found to be increased in patients with any type of antibody,
although they were most numerous in those with both types of antibodies. Seven of 123 patients (6%) had
coeliac disease (three previously diagnosed). Patients with antibodies who adhered to the GFD displayed
total or nearly total clearance of the skin lesions and normalization of the antibody levels. CONCLUSIONS:
Patients with PPP should be screened for antibodies against gliadin and tTG. Those with antibodies
can be much improved on a GFD regardless of the degree of mucosal abnormalities."

Palmoplantar pustulosis is a condition highly correlated to gluten sensitivity.

Skin Disorders

Gluten intolerance and skin diseases.
1: Eur J Dermatol. 2006 Jan-Feb;16(1):4-11.PMID: 16436335

Full Citation: "Gluten sensitivity with or without coeliac disease (CD) symptoms and intestinal pathology has
been suggested as a potentially treatable cause of various diseases. CD is a chronic disease which improves
on withdrawal of wheat gliadins and barley, rye and oat prolamins from the diet. There have been numerous
reports linking CD with several skin conditions. A body of evidence shows that dermatitis herpetiformis is
actually a cutaneous manifestation of CD. Autoimmune diseases, allergic diseases, psoriasis and
miscellaneous diseases have also been described with gluten intolerance. Dermatologists should be familiar
with the appraisal of gluten sensitive enteropathy and should be able to search for an underlying gluten
intolerance (GI). Serological screening by means of antigliadin, antiendomysial and transglutaminase
antibodies should be performed. HLA typing is often useful in association with serologic tests. Intestinal
biopsy is usually needed to establish the diagnosis of CD or GI. Thus, gluten intolerance gives rise to a
variety of dermatological manifestations which may benefit from a gluten-free diet."

Gluten intolerance may manifest in a variety of skin diseases.

Putting the pieces of the puzzle together - a series of hypotheses on the etiology and
pathogenesis of type 1 diabetes.
1: Med Hypotheses. 2007;68(3):607-19. Epub 2006 Oct 11 PMID: 17045415

Full Citation: "This paper presents a series of 10 hypotheses on the etiology of type 1 diabetes. We begin
with the hypothesis that wheat gluten is one of the elusive environmental triggers in type 1 diabetes. Habitual
consumption of wheat gluten increases the intestinal synthesis of dipeptidyl peptidase IV. This enzyme helps
to shape the repertoire of peptides released into the small intestine following the ingestion of wheat gluten by
catalyzing the release of X-Pro dipeptides from the N-terminus of the proline-rich glutenins and gliadins in
wheat gluten. The release of gluten-derived peptides causes the tight junctions of the small intestine to open
through a zonulin-dependent mechanism, which allows these peptides to enter the lamina propria where they
get presented as antigens by HLA-DQ, -DR and CD1d molecules. Binding of one or more gluten peptides by
CD1d leads to abrogation of oral tolerance, and a marked increase in peripheral immune responses to wheat
proteins. Furthermore, it is our contention, that in response to beta cell apoptosis during normal remodeling
of the pancreas and CCL19/CCL21 expression within the pancreatic lymph nodes (PLNs), gluten-loaded
dendritic cells migrate from the small intestine to the PLNs. These dendritic cells present gluten-derived
antigens on the surface of the PLNs, which leads to migration of CD4(-)CD8(-) gammadelta and
CD4(-)CD8(+) alphabeta T cells to the pancreas where they mediate Fas and perforin dependent
cytotoxicity. We also hypothesize that at least one of the type 1 diabetes associated HLA-DR molecules that
bind and present wheat-derived peptide(s) also bind and present an islet cell antigen(s), activating plasma
cell synthesis of islet cell autoantibodies and irrevocable, complement-dependent destruction of islet cells.
Our final two hypotheses state that type 1 diabetes morbidity is reduced in those areas of globe where
genetically susceptible individuals get adequate amounts of vitamin D, in the diet and/or through exposure to
sunlight, and in areas where people are exposed to bacterial, viral, or parasitic infections in early childhood."

The habitual consumption of wheat gluten is a contributing factor in the pathogenesis of
type 1 diabetes.

Diabetes

Serologic markers of celiac disease in psoriatic patients.
1: J Eur Acad Dermatol Venereol. 2008 Sep;22(9):1055-61. Epub 2008 Apr 1. PMID: 18384553

Full Citation: "BACKGROUND: Aetiopathogenesis of psoriasis is complex and not yet well known. In recent
years, it has been observed that psoriasis can coexist with clinically asymptomatic celiac disease and a
gluten-free diet helps to obtain remission, even in patients with very chronic lesions. OBJECTIVE: The aim of
our work was to investigate how often the positive titres of antibodies characteristic for celiac disease occur in
psoriatics' serum in exacerbation in comparison with controls. PATIENTS/METHODS: Serum samples from 67
patients with intensified psoriatic lesions were investigated. Serum from healthy people at a comparable age
and with no familial predisposition to psoriasis and celiac disease was the control material. Antibodies against
human tissue transglutaminase (recombinant antigen), against tissue transglutaminase isolated from guinea
pig's liver and against gliadin were determined by enzyme-linked immunosorbent assay technique.
Anti-endomysial antibodies were determined by indirect immunofluorescence method. RESULTS: Patients
with psoriasis have significantly higher mean concentrations of antibodies against tissue transglutaminase
(human recombinant and guinea pig-derived antigen) and against gliadin for IgA. IgA antibodies against
tissue transglutaminase (both antigens) and gliadin positively correlate with psoriasis activity. No
anti-endomysial antibodies for IgA were found in any serum. CONCLUSIONS: Our results seem to imply an
association between psoriasis and asymptomatic celiac disease/gluten intolerance. High percentage of
positive results to guinea pig-derived tTG could be due to cellular activity of tissue transglutaminase
in psoriasis."

There is an association between psoraisis and asymptomatic celiac disease/gluten
intolerance.

Prospective screening for coeliac disease in patients with Graves'
hyperthyroidism using anti-gliadin and tissue transglutaminase
antibodies.
1: Clin Endocrinol (Oxf). 2005 Mar;62(3):303-6.Click here to read PMID:
17322576

Full Citation: "INTRODUCTION: Coeliac disease (CD) is associated with autoimmune thyroid
disease (AITD) although its prevalence among those with Graves' hyperthyroidism in the UK is
unknown. We determined the prevalence and evaluated the role of screening for CD
prospectively in a consecutive cohort of patients with Graves' hyperthyroidism using IgA class
antibodies to gliadin (AGA) and tissue transglutaminase (anti-tTG). METHODS: All patients with
Graves' hyperthyroidism attending the thyroid clinic over a 9-month period were offered
screening for CD using AGA (normal < 3 mg/l) and anti-tTG (normal < 15 micro/ml).
Comparison was made with an age- and sex-matched healthy control group from the local
population whose sera were tested for anti-tTG. In patients with borderline or raised anti-tTG
(> 7 micro/ml) endomysial antibody (EmA) was measured. Serum IgA was also measured to
exclude IgA deficiency. Patients with raised AGA, raised or borderline anti-tTG, positive EmA,
IgA deficiency or haematinic deficiencies were offered endoscopic duodenal biopsy. RESULTS:
A total of 115 patients (97 female and 18 male) with Graves' hyperthyroidism were offered
screening tests and 111 accepted. AGA was raised in 15 patients, anti-tTG was raised in two
(both positive for EmA) and equivocal in six (one positive for EmA). IgA deficiency was present
in three. Four patients were known to have haematinic deficiencies. Twenty-five patients were
invited and 19 agreed to have endoscopic duodenal biopsy. Three new patients were found to
have CD while two patients were already known to have CD, thus five of 111 patients with
Graves' hyperthyroidism had CD. One of 115 healthy controls had a strong positive anti-tTG (>
200 micro/ml) and EmA indicating probable CD. CONCLUSIONS: Screening 111 consecutive
patients with Graves' hyperthyroidism revealed AGA in 14%, anti-tTG in 2% and IgA
deficiency in 3%. Two patients were known to have CD. Screening detected three new
cases. The prevalence of CD in patients with Graves' hyperthyroidism was 4.5% as
compared with 0.9% in matched healthy controls. Routine screening for CD should be
considered."

Celiac disease is far higher in those diagnosed with Grave's disease.

Grave's disease

High rate of positive anti-tissue transglutaminase antibodies in chronic
liver disease. Role of liver decompensation and of the antigen source.
1: Scand J Gastroenterol. 2003 Jan;38(1):50-4. PMID: 12608464

Full Citation: "BACKGROUND: Since the recognition of tissue transglutaminase (tTG) as the
target antigen of anti-endomysium antibodies, several ELISA assays using either guinea pig or
human recombinant tTG have been developed. The aim of the study was to compare the
behaviour of anti-tTG and anti-endomysium antibodies assays in coeliacs and in patients with
chronic liver disease. METHODS: 34 patients (24 women, 34.9 +/- 12.5 years) with coeliac
disease and 41 with chronic liver disease (14 women, 57 +/- 11.2 years), including 19
cirrhotics, were evaluated for anti-endomysium antibodies by indirect immunofluorescence and
for anti-tTG IgA antibodies by ELISA, using guinea pig liver or human recombinant
transglutaminase. RESULTS: The prevalences of anti-tTG and anti-endomysium antibodies
were 100% in patients with coeliac disease at diagnosis, 75% and 64.3% in patients on a
gluten-free diet. All liver disease patients were negative for anti-endomysium antibodies, while
11 (26.8%) were positive for anti-tTG. All these patients had liver cirrhosis and represented
57.9% of all cirrhotics. The presence of anti-tTG was associated with higher Child-Pugh
scores. The use of human transglutaminase determined a reduction in the rate of positive
results; however, the rate of positive anti-tTG was still 17.1% in all liver disease patients and
31.6% in cirrhotics. CONCLUSIONS: Our data confirm that anti-tTG have a similar
sensitivity compared with anti-endomysium antibodies assay in coeliacs. However, a high
prevalence of positive anti-tTG results is observed in cirrhotic patients, even when
human recombinant tTG is used. The high prevalence of positive results among
cirrhotic patients is associated with more advanced liver disease."

Patients with chronic liver disease have a high prevalence of anti-tTg antibodies, similar
to patients with celiac disease.

Liver disease

Gluten-free diet in psoriasis patients with antibodies to gliadin results in decreased
expression of tissue transglutaminase and fewer Ki67+ cells in the dermis.
1: Acta Derm Venereol. 2003;83(6):425-9. PMID: 14690336

A Gluten-free diet in psoriasis patients with antibodies to gliadin results in significant
clinical improvements.

Full Citation: "Previous studies have shown that 16% of patients with psoriasis vulgaris have IgA and/or
IgG antibodies to gliadin, but few have antibodies to endomysium. The increase in duodenal
intraepithelial lymphocytes was mild. Still, highly significant clinical improvement was observed after 3
months on a gluten-free diet. This study surveys certain immunohistological aspects of involved and
non-involved skin in 28 AGA-positive psoriasis patients before and after 3 months of a gluten-free diet.
Staining was performed for CD4+ T lymphocytes, Langerhans' cells, endothelium, proliferating (Ki67)
cells and tissue transglutaminase. In the entire group of patients, as well as in those on a gluten-free
diet as the only treatment, Ki67 + cells in involved dermis were highly significantly decreased after the
diet. There was a significant decrease in Ki67 + cells even in patients without increased intraepithelial
lymphocytes. Tissue transglutaminase was highly overexpressed in involved skin in the papillary
endothelium, and decreased by 50% after gluten-free diet. The possible role of tissue
transglutaminase in the pathogenesis of psoriasis needs further investigation."

There is a weak but positive correlation with the presence of coronary heart
disease and the presece of anti-gliadin antibodies.

Cardiovascular Disease

Full Citation: "The aim of this study was to search to the factors favouring the earlier revealing of a
coronary artery disease by comparing selected immunological, hormonal and biochemical
parameters between two groups--younger and older men with coronary artery disease and with
responding control groups. MATERIAL AND METHODS: In the study were included 93 men--60 with
stable angina, confirmed by coronarography (at least 6 months after CABG, PTCA or myocardial
infraction, with EF > 40%) and 33 men without atherosclerotic changes in the coronary vessels, as
the control group. The two groups were divided depending on age: the younger subgroups [under
60-ty years old--group A with CAD (n=30) and B without CAD (n=18)] and the older subgroup [over
70-ty years old group C with CAD (n=30) and D without CAD (n=15)]. RESULTS: Significantly lower
concentration were noted for TNF-alpha--in control groups--by about 50% in the younger and 23%
in the older group (r = 0.49) and homocysteine (by about 20% and 22% respectively, r = 0.40).
Patients with CAD had higher concentration of CRP then in the control groups (by 52% and 54%, r =
0.28). Weak but positive correlation with the presence of a coronary heart disease was show
for IgE and anti-gliadin antibodies (r = 0. 22-0.29). CONCLUSION: The younger and older men
with CAD statistically significantly differed in concentration of TNF-alpha and homocysteine."

[The some risk factors for atherosclerosis in men with coronary artery
disease depending on the age]
1: Pol Merkur Lekarski. 2007 Jul;23(133):9-14.
PMID: 18051823

Cardiomyopathy may be associated with celiac disease in some cases and may respond
well to a gluten-free diet.

Full Citation: "Celiac disease or celiac sprue is predominantly a disease of the small intestine
characterized by chronic malabsorption in genetically susceptible individuals who ingest grains
containing gluten, such as wheat, barley, and rye. Although previously believed to be uncommon,
celiac disease may be present in up to 1% of the general population. Celiac disease is associated
frequently with iron deficiency anemia, dermatitis herpetiformis, selective IgA deficiency, thyroid
disorders, diabetes mellitus, and various connective tissue disorders but is rarely associated with
cardiomyopathy. We describe a patient with celiac disease associated with cardiomyopathy whose
cardiac function improved substantially after treatment with a gluten-free diet. Cardiomyopathy
associated with celiac disease is a serious and potentially lethal condition. However, with early
diagnosis and treatment with a gluten-free diet, cardiomyopathy in patients with celiac disease may
be completely reversible."

Cardiomyopathy associated with celiac disease.
1: Mayo Clin Proc. 2005 May;80(5):674-6.
PMID: 15887437