Antigliadin Antibodies

The Gluten File



So we are told isolated anti-gliadin antibodies are non-specific, and therefore regarded as meaningless by most doctors, particularly AGA IgG antibodies.  That leaves us (at least me) wondering what other conditions are associated with antigliadin antibodies. I went looking~ and found the following. 

Curious minds want to know~

Do antigliadin antibodies suggest gluten sensitivity may be involved in diseases other than Celiac Disease? If gluten can cause Celiac Disease, why is it such a far stretch to consider it might be directly relevant in other autoimmune disease? If gluten sensitivity can cause autoimmune disease, what about a similar response to other foods? Casein? Soy?

Association does not prove cause, granted. BUT, it is interesting to me that so many of these other conditions have not only increased associations with Celiac Disease, but anecdotal reports (and a few medical journal reports, to boot) of some of these patients with other autoimmune conditions improving on a gluten free diet. When other conditions improve or resolve on a gluten free diet, what does that say???

I sure don't have all the answers, but I provide this page in response to the doctor's who say antigliadin IgG or IgA antibodies are non-specific, but leave us wondering what "other" conditions they are seen in. Can't wait to see where the research has taken us in another ten years!


Meaningless? I don't think so!


Testing for gluten-related disorders in clinical practice: The role of serology in managing the spectrum of gluten sensitivity.

PMID:21523259  April 2011

Antigliadin immunoglobulin A best in finding celiac disease in children younger than 18 months of age. 
PMID: 18852634   Oct 2008

Gliadin IgG antibodies and circulating immune complexes.
PMID: 18819035   2009


ANTIGLIADIN ANTIBODIES ARE COMMONLY SEEN IN:


Bipolar Disorder

Conclusions:  Individuals with bipolar disorder have increased levels of IgG antibodies to gliadin. However, such antibody increase is not accompanied by an elevation in IgA antibodies to gliadin or the celiac disease-associated antibodies against deamidated gliadin and tTG. These results warrant further detailed examination of the molecular specificity and pattern of reactivity of the antibody response to gluten antigens in bipolar disorder.
Markers of gluten sensitivity and celiac disease in bipolar disorder.
PMID: 21320252  Feb 2011

Crohn's Disease
High prevalence of celiac disease among patients affected by Crohn's disease. PMID: 15973121 July 2005

Diabetes
RESULTS: 17 [out of 34] patients had elevated IgG AGA, none showed elevated IgA AGA. Only one patient had elevated IgA and anti tTG levels, and a normal small intestinal biopsy. 28 patients had HLA DQ2 or DQ8 present.
Celiac disease in African American children with type 1 diabetes mellitus in inner city Brooklyn.
PMID: 18806716   Aug 2008

We found a significantly higher occurrence of gliadin antibodies in LADA patients: the rate of AGGAb was 19.1% in comparison with 3.5% in the T2DM group (P = 0.0026), the rate of AGAAb was 13.2% in comparison with 3.5% (P = 0.035). The prevalence of EMAb was very low in both groups (1.5% and 0).
Gliadin, endomysial and thyroid antibodies in patients with latent autoimmune diabetes of adults (LADA).http://www.ncbi.nlm.nih.gov/pubmed/12823288 PMID: 12823288 July 2003

[Risk markers for insulin-dependent diabetes mellitus and duration of exposure to gluten in celiac patients] PMID: 15478300 Aug 2004

Down Syndrome
Down syndrome and coeliac disease: usefulness of antigliadin and antiendomysium antibodies.
PMID: 9001668 Dec 1996

Prevalence of IgA-antigliadin antibodies and IgA-antiendomysium antibodies related to celiac disease in children with Down syndrome.
PMID: 9445503 Feb 1998

Depression
Conclusions. Although AGA positivity is of clinical relevance only in a subset of elderly people, it seems to be related to rheumatoid arthritis and depression, both conditions linked to celiac disease. Further studies are needed to reveal the mechanisms underlying this. The poor specificity of AGA for celiac disease was here once more in evidence.  
Positive serum antigliadin antibodies without celiac disease in the elderly population: does it matter?
PMID: 20545470 June 2010

IgA Deficiency
Role of human-tissue transglutaminase IgG and anti-gliadin IgG antibodies in the diagnosis of coeliac disease in patients with selective immunoglobulin A deficiency. PMID: 15571003 Nov 2004

Irritable Bowel Syndrome

The mechanism by which food activates mucosal immune system is uncertain, but food specific IgE and IgG4 appeared to mediate the hypersensitivity reaction in a subgroup of IBS patients. Exclusion diets based on skin prick test, RAST for IgE or IgG4, hypoallergic diet and clinical trials with oral disodium cromoglycate have been conducted, and some success has been reported in a subset of IBS patients.
Is there a role of food allergy in irritable bowel syndrome and functional dyspepsia? A systematic review.
 
PMID: 16918724 Aug 2006


Determination of the level of specific markers of celiac disease (in our research--antigliadin Ig) is considered to be the optimal method of diagnostic celiac disease in this group of patients.
[Prevalence of undiagnosed celiac disease in patients with irritated bowel syndrome] 
PMID: 14723137  Oct 2003


Liver Disease
Antigliadin antibody classes in chronic liver disease.
PMID: 1421449 Oct 1992

MS
Results - Highly significant increases compared with controls were found for IgA and IgG antibodies against gliadin and gluten. IgA antibodies against casein were significantly increased. Anti-endomycium and anti-transglutaminase antibodies were negative.
IgA antibodies against gliadin and gluten in multiple sclerosis.
PMID: 15355487 Oct 2004

Psoriasis
Coeliac disease-associated antibodies correlate with psoriasis activity.
PMID: 15491433 Oct 2004

[The significance of diet and associated factors in psoriasis.]
PMID: 16758223 June 2006

Rheumatoid Arthritis

Conclusions. Although AGA positivity is of clinical relevance only in a subset of elderly people, it seems to be related to rheumatoid arthritis and depression, both conditions linked to celiac disease. Further studies are needed to reveal the mechanisms underlying this. The poor specificity of AGA for celiac disease was here once more in evidence.  
Positive serum antigliadin antibodies without celiac disease in the elderly population: does it matter?
PMID: 20545470 June 2010

[Antigliadin antibodies in rheumatoid arthritis]
PMID: 8293004 Mar 1993

Gliadin immune reactivity in patients with rheumatoid arthritis.
PMID: 8575138 Sept 1995

Schizophrenia

RESULTS: Individuals with recent-onset psychosis had increased levels of IgG (odds ratio [OR] 5.50; 95% confidence interval [CI] 2.65-11.42) and IgA (OR 2.75; 95% CI 1.31-5.75) antibodies to gliadin compared with control subjects. Individuals with multi-episode schizophrenia also had significantly increased levels of IgG antibodies to gliadin (OR 6.19; 95% CI 2.70-14.16). IgG antibodies to deamidated gliadin and IgA antibodies to tissue transglutaminase were not elevated in either psychiatric group, and fewer than 1% of individuals in each of the groups had levels of these antibodies predictive of celiac disease. There were no significant differences in the distribution of the HLA DQ2/8 alleles among the groups. CONCLUSIONS: Individuals with recent-onset psychosis and with multi-episode schizophrenia who have increased antibodies to gliadin may share some immunologic features of celiac disease, but their immune response to gliadin differs from that of celiac disease.
Markers of Gluten Sensitivity and Celiac Disease in Recent-Onset Psychosis and Multi-Episode Schizophrenia.
Biol Psychiatry
. 2010 May 13. [Epub ahead of print]
PMID: 20471632
  May 2010

A link between celiac disease and schizophrenia has been postulated for several years, based primarily on reports of elevated levels of antibody to gliadin in patients. We sought to examine the proposed connection between schizophrenia and celiac disease by characterizing the molecular specificity and mechanism of the anti-gliadin immune response in a subset of individuals with schizophrenia. Blood samples from individuals with schizophrenia and elevated anti-gliadin antibody titer were examined for celiac disease-associated biomarkers, including antibodies to transglutaminase 2 (TG2) enzyme and deamidated gliadin peptides, as well as the HLA-DQ2 and -DQ8 MHC genes. The anti-gliadin antibody response was further characterized through examination of reactivity towards chromatographically separated gluten proteins. Target proteins of interest were identified by peptide mass mapping. In contrast to celiac disease patients, an association between the anti-gliadin immune response and anti-TG2 antibody or HLA-DQ2 and -DQ8 markers was not found in individuals with schizophrenia. In addition, the majority of individuals with schizophrenia and anti-gliadin antibody did not exhibit antibody reactivity to deamidated gliadin peptides. Further characterization of the antibody specificity revealed preferential reactivity towards different gluten proteins in the schizophrenia and celiac disease groups. These findings indicate that the anti-gliadin immune response in schizophrenia has a different antigenic specificity from that in celiac disease and is independent of the action of transglutaminase enzyme and HLA-DQ2/DQ8. Meanwhile, the presence of elevated levels of antibodies to specific gluten proteins points to shared immunologic abnormalities in a subset of schizophrenia patients. Further characterization and understanding of the immune response to gluten in schizophrenia may provide novel insights into the etiopathogenesis of specific disease phenotypes.
Novel immune response to gluten in individuals with schizophrenia. 
PMID: 19748229  Sept 2009

Autoantibodies associated with psychiatric disorders.
PMID: 16719797 May 2005
[could not find anything specific to antigliadin antibodies...but several newer studies looking at schizophrenia as an immune mediated disease]

The gluten connection: the association between schizophrenia and celiac disease.
PMID: 16423158 Feb 2006

More schizophrenics than controls showed IgA antibody levels above the upper normal limit to gliadin, beta-lactoglobulin, and casein.
Specific IgA antibody increases in schizophrenia.
PMID: 7772650 Mar 1995


SLE
The prevalence of antigliadin antibodies in patients with SLE has been reported to be 23%.14 None of these patients had an enteropathy on biopsy. The conclusion was that there is no association between CD and SLE, but an association between gluten sensitivity and SLE cannot be excluded. More likely, however, is the possibility of misdiagnosis of SLE in patients with gluten sensitivity.
Gluten sensitivity masquerading as systemic lupus erythematosus Feb 2004

Sjogren's
Even among nonceliac patients with primary Sjogren'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 Sjogren's syndrome.
PMID: 10201480 April 1999

Thyroid disease
The presence of the antigliadin antibodies in autoimmune thyroid diseases. PMID: 15244201 Dec 2003

Ulcerative Colitis
High frequency of antigliadin antibodies and absence of antireticulin and antiendomysium antibodies in patients with ulcerative colitis.
PMID: 10204612 Feb 1999

 
OTHER

Antigliadin antibodies (AGA) mark celiac disease, but AGA are also encountered in IgA-nephritis, psoriasis, sickle-cell anemia, hepatic disorders, juvenile rheumatoid arthritis, autoimmune thyroidism and in persons who occupationally contact great amounts of wheat. AGA IgA and/or IgG were registered in 19 of 60 subjects (51 adults and 9 children) with various immunomediated diseases without symptoms of celiac disease: in 4 cases of chronic active hepatitis, in 2 of 4 cases of chronic persistent hepatitis, in 4 of 16 cases of rheumatoid arthritis, in 3 of 19 cases of IgA-deficiency, in 1 of 8 cases of SLE, in 2 cases of postvaccine reaction, in all the single cases of juvenile rheumatoid arthritis, focal scleroderma, macroglobulinemia. IgA only occurred in in 6 patients, IgG- in 6 patients, both IgA and IgG in 7 patients. The most pronounced positive reaction to AGA was recorded in 8-year-old girl with juvenile rheumatoid arthritis. The emergence of AGA in immunomediated diseases may be attributed to the response to food protein in pathological conditions and is often unrelated closely with celiac disease.
[Antigliadin antibodies in the absence of celiac disease]
PMID: 9553358 1998

Our results showed that while AGA-IgA were absent in all children studied, with the exception of 3 cases of acute diarrhoea, a moderate percentage of AGA-IgG was observed in subjects with cow's milk protein intolerance, acute diarrhoea, irritable bowel syndrome, lactase deficiency, chronic intractable diarrhoea and in a low percentage of children with parasitosis, intestinal lymphangiectasia and nodular lymphoid hyperplasia.
The predictive value of antigliadin antibodies (AGA) in the diagnosis of non-celiac gastrointestinal disease in children]
PMID: 8341233 Mar 1993

CONCLUSIONS: IgA-class antireticulin or antigliadin antibody-positive patients with normal small-bowel mucosal morphology frequently have immunohistochemical markers of coeliac disease latency. Together with our follow-up data this implies that they may be gluten-sensitive.
Small-bowel mucosal inflammation in reticulin or gliadin antibody-positive patients without villous atrophy.
PMID: 9759950 Sept 1998

We describe a unique case of atypical natural killer (NK)-cell proliferation likely related to gluten sensitivity, mimicking NK-cell lymphoma. >>> Two years after initial presentation, the patient was found to have high titers of antigliadin antibodies with no other evidence of celiac disease. After instituting a gluten-free diet, many of the lesions regressed, suggesting that this atypical NK-cell proliferation may be driven by an anomalous immune response. Awareness of this case may prevent pathologists from misdiagnosing similar lesions as NK/T-cell lymphomas. It is as yet unknown whether this process occurs more commonly in patients with gluten sensitivity, or in other settings, and the pathogenesis is as yet undetermined.
Atypical NK-cell proliferation of the gastrointestinal tract in a patient with antigliadin antibodies but not celiac disease.
PMID: 16625103 April 2006

CONCLUSION: We show that Caucasian Argentine women with RPL showed significantly higher incidence of anticardiolipin antibodies than normal controls and finally we recommended the screening of IgA and IgG antigliadina and IgA antitransglutaminase antibodies in pregnancy, because of the high prevalence of subclinical CD in RPL and the chance of reversibility through consumption of a gluten free diet.
Autoantibodies in Argentine women with recurrent pregnancy loss.
PMID: 16451354  March 2006

Longitudinal follow-up examination of antigliadin antibody positive children and adults.
PMID: 16607144 May 2006

Antigliadin antibodies associated with chronic mucocutaneous candidiasis.
PMID: 12383098 Sept 2002


 


From: The Neurology of Gluten Sensitivity: Science vs. Conviction
by Hadjivassiliou and Grunewald  2004

"There is also confusion about the role of antigliadin antibodies as a screening tool. Given that gluten sensitivity can exist without enteropathy, it is inappropriate to estimate sensitivity and specificity of these antibodies against the presence of enteropathy as the 'gold standard'. To assert that antigliadin antibodies lack specificity based on the fact that 10% of the healthy population may have them is a misconception. It is entirely plausible that 10% of the healthy population with circulating antigliadin antibodies have gluten sensitivity without recognized manifestations. The prevalence of coeliac disease itself is now recognized to be 20 times higher than what it was thought to be 20 years ago because most cases are clinically silent. It is important to realize that amongst the 10% antigliadin antibody positive people lurks those with 'silent' gluten sensitive enteropathy."

"It is ill-considered to suggest that antigliadin antibodies should not be used as a screening tool because they are found in “healthy” individuals. It is also irresponsible to suggest that neurological patients should not be screened for coeliac disease unless additional factors are present such as unexplained anaemia or evidence of malabsorption."

"Neurologic manifestations of gluten sensitivity are a scientific fact, not a theological issue. Whilst the debate continues, we owe it to our patients to screen them effectively for gluten sensitivity with the simple widely available antigliadin antibody test so that we do not in the meantime deprive them of a harmless but potentially effective treatment in the form of a gluten-free diet."