In the U.S., public awareness of gluten free diets has reached widespread recognition, but largely in name only. For those suffering with celiac disease or acute wheat allergies, it’s critical. For those with known reactions to gluten, it’s of serious importance. For those who don’t really know what it’s about, but see it on packaging, it seems to evoke a similar response as being forced to “Press 1 for English”. Journalists tend to frame the gluten free approach as legit for celiac treatment, but ultimately a fad diet controlling minions of mindless Gwyneth Paltrow lovers (AP Article). The paleo diet community views it as more of a religion (that’s tongue-in-cheek hyperbole, people!). Before we continue, here are my biases: I experience repeatable, specific, and boring symptoms from gluten intake, but I do not have celiac disease or a “gluten allergy”. Evolutionary biology is a scientific fact and I believe the paleo diet provides ultimate explanations for why we should’t eat grains. So what are the proximate explanations for going gluten free? Is it fad or fo’ real?

A quick and dirty primer

Celiac (or coeliac) disease is an autoimmune disorder in which the small intestine is damaged by components of gluten, a protein found in wheat and other grains. The effects of celiac diseas are numerous, serious, and varied. For a entertaining sobering look, check out Tim Ferriss’ How to Keep Feces Out of Your Bloodstream. Strictly speaking, a “wheat allergy” can be similar to something like a peanut allergy. Folks in this group experience rapid onset symptoms that are serious, including the potential of anaphylactic shock. It’s mainly for these folks that food is required to expose the presence of wheat content on packaging.

From there, we transition into the murky terms of gluten intolerance and/or sensitivity. These two classifications are where the non-celiac, non-allergy folks may reside. Whether we should take them seriously is what the references below try to answer. There’s plenty of research and anecdotal evidence within the paleo and related nutrition/health worlds. However, since they’re in it for the money, some people tend to pass what they say off as mere profiteering. And perhaps that’s fair, but perhaps both are justified.

Below are a series of links (and abstracts when available) to recent medical literature on gluten research. Basically, I just did a search on PubMed for articles with “gluten” in the title, but without “celiac” or “coeliac” in the title. Doing this search brought up 1340+ results, so I narrowed it down. I’ve tried to filter out the articles discussing the use of gluten free diets in the treatment of autism. I’ve also endeavored to filter out everything relating to animal studies. That said, some of the animal studies are quite convincing… But I get it… Humans aren’t chimpanzees or mice. Also, I only went back to 2008 (this was written in September, 2010).

For those not familiar with medical journals, this sort of research can be beyond frustrating. Realize that you have to pay for the full versions of most of these articles if you’re not a member of an organization (University, Hospital, etc.) with a subscription. For the sake of expediency, I’m going to bias this thing like crazy and highlight (in red) some of the more salient points below. Reading only the titles and highlighted passages will give you maximum bias if that’s what you’re looking for. To get the full story, you’d need to read all of every article.

Current Barometer

My assessment of the current barometer for medical research on the effect of gluten on humans is roughly this: In the general population (those not having celiac disease or wheat allergies), gluten either causes, or is strongly correlated to a range of autoimmune and neurological disorders. Further, gluten intolerance can present with any one, or group, of symptoms or disorders with varying degrees of severity. Lastly, it is generally agreed that celiac disease and non-celiac gluten intolerance are underreported and under-diagnosed, though the numbers remain speculative.

For me, on a practical level, the correlations between autoimmune and neurological problems in the scientific literature, my personal experiences with gluten, anecdotal reports from others, and the logical framework of evolutionary biology/paleo diet is convincing enough for me to abstain from gluten.

Medical Journal References to Gluten in Non-Celiac Individuals

Gluten Causes Gastrointestinal Symptoms in Subjects Without Celiac Disease – The American Journal of Gastroenterology

Abstract

OBJECTIVES: Despite increased prescription of a gluten-free diet for gastrointestinal symptoms in individuals who do not have celiac disease, there is minimal evidence that suggests that gluten is a trigger. The aims of this study were to determine whether gluten ingestion can induce symptoms in non-celiac individuals and to examine the mechanism.

METHODS: A double-blind, randomized, placebo-controlled rechallenge trial was undertaken in patients with irritable bowel syndrome in whom celiac disease was excluded and who were symptomatically controlled on a gluten-free diet. Participants received either gluten or placebo in the form of two bread slices plus one muffin per day with a gluten-free diet for up to 6 weeks. Symptoms were evaluated using a visual analog scale and markers of intestinal inflammation, injury, and immune activation were monitored.

RESULTS: A total of 34 patients (aged 29-59 years, 4 men) completed the study as per protocol. Overall, 56% had human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8. Adherence to diet and supplements was very high. Of 19 patients (68%) in the gluten group, 13 reported that symptoms were not adequately controlled compared with 6 of 15 (40%) on placebo (P=0.0001; generalized estimating equation). On a visual analog scale, patients were significantly worse with gluten within 1 week for overall symptoms (P=0.047), pain (P=0.016), bloating (P=0.031), satisfaction with stool consistency (P=0.024), and tiredness (P=0.001). Anti-gliadin antibodies were not induced. There were no significant changes in fecal lactoferrin, levels of celiac antibodies, highly sensitive C-reactive protein, or intestinal permeability. There were no differences in any end point in individuals with or without DQ2/DQ8.

CONCLUSIONS: “Non-celiac gluten intolerance” may exist, but no clues to the mechanism were elucidated.

Sensory ganglionopathy due to gluten sensitivity – Neurology, 2010

Abstract

OBJECTIVES: Gluten sensitivity can engender neurologic dysfunction, one of the two commonest presentations being peripheral neuropathy. The commonest type of neuropathy seen in the context of gluten sensitivity is sensorimotor axonal. We report 17 patients with sensory ganglionopathy associated with gluten sensitivity.

METHODS: This is a retrospective observational case series of 17 patients with sensory ganglionopathy and gluten sensitivity. All patients had been followed up for a number of years in dedicated gluten sensitivity/neurology and neuropathy clinics.

RESULTS: Out of a total of 409 patients with different types of peripheral neuropathies, 53 (13%) had clinical and neurophysiologic evidence of sensory ganglionopathy. Out of these 53 patients, 17 (32%) had serologic evidence of gluten sensitivity. The mean age of those with gluten sensitivity was 67 years and the mean age at onset was 58 years. Seven of those with serologic evidence of gluten sensitivity had enteropathy on biopsy. Fifteen patients went on a gluten-free diet, resulting in stabilization of the neuropathy in 11. The remaining 4 had poor adherence to the diet and progressed, as did the 2 patients who did not opt for dietary treatment. Autopsy tissue from 3 patients demonstrated inflammation in the dorsal root ganglia with degeneration of the posterior columns of the spinal cord.

CONCLUSIONS: Sensory ganglionopathy can be a manifestation of gluten sensitivity and may respond to a strict gluten-free diet.

Gluten sensitivity and the CNS: diagnosis and treatment – Lancet Neurology, 2010

Abstract

Gluten sensitivity is a systemic autoimmune disease with diverse manifestations. This disorder is characterised by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Coeliac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible manifestations of gluten sensitivity. Although neurological manifestations in patients with established coeliac disease have been reported since 1966, it was not until 30 years later that, in some individuals, gluten sensitivity was shown to manifest solely with neurological dysfunction. Furthermore, the concept of extraintestinal presentations without enteropathy has only recently become accepted. In this Personal View, we review the range of neurological manifestations of gluten sensitivity and discuss recent advances in the diagnosis and understanding of the pathophysiological mechanisms underlying neurological dysfunction related to gluten sensitivity.

GAD antibody-associated neurological illness and its relationship to gluten sensitivity. – Acta Neurologica Scandinavica, 2010

Abstract

Background – The high prevalence of gluten sensitivity in patients with stiff-person syndrome (SPS) lead us to investigate the relationship between gluten sensitivity and GAD-antibody-associated diseases. Methods – We used ELISA assays for anti-GAD and for serological markers of gluten sensitivity. Patients were recruited from clinics based at the Royal Hallamshire hospital, Sheffield, UK. Patients with gluten sensitivity were followed up after the introduction of a gluten-free diet and serological testing was repeated. Results – Six of seven (86%) patients with SPS were positive for anti-GAD, mean titre 109 U/ml; This compared with 9/90 (11%) patients with idiopathic sporadic ataxia, mean titre 32 U/ml, 16/40 (40%) patients with gluten ataxia, mean titre 25 U/ml, and 6/10 patients with type 1 diabetes only, mean titre 8 U/ml. None of 32 patients with celiac disease only, and of 40 patients with genetic ataxia were positive for anti-GAD. The titre of anti-GAD reduced following the introduction of a gluten-free diet in patients with SPS who had serological evidence of gluten sensitivity. The same was observed in patients with gluten ataxia and anti-GAD antibodies. This was also associated with clinical improvement. Conclusion – These findings suggest a link between gluten sensitivity and GAD antibody-associated diseases.

Genetic and immunological processes in the pathomechanism of gluten-sensitive enteropathy and associated metabolic bone disorders – Orvosi Hetelap, 2010

Abstract

Celiac disease or gluten-sensitive enteropathy is the most common disease of jejunum, leading to malabsorption. It is an immune mediated disease induced by gluten at the presence of genetic predisposition. After gluten exposition, immune processes are induced by T-cell mediation causing typical intestinal and extra intestinal manifestations. The diagnosis of celiac disease is still set up on the result of jejunal biopsy and detecting of antibodies against endomysium and tissue transglutaminase. From genetic aspect, association with HLA DQ2/DQ8 is identified in celiac disease. On a strict gluten-free diet, the clinical, histological and serological results improve and remission of accompanying diseases may be achieved. In the etiopathogenesis of celiac disease several genetic and immunological mechanisms have been recognized in recent years. Connected to the accompanying diseases, more reviews have been issued about the bone metabolic changes and less about the inflammatory join disorders. In the present work, the authors review literature data that reveal common background from both immunological and genetic aspects.

Gluten sensitivity: from gut to brain – Lancet Neurology, 2010

Abstract

Gluten sensitivity is a systemic autoimmune disease with diverse manifestations. This disorder is characterised by abnormal immunological responsiveness to ingested gluten in genetically susceptible individuals. Coeliac disease, or gluten-sensitive enteropathy, is only one aspect of a range of possible manifestations of gluten sensitivity. Although neurological manifestations in patients with established coeliac disease have been reported since 1966, it was not until 30 years later that, in some individuals, gluten sensitivity was shown to manifest solely with neurological dysfunction. Furthermore, the concept of extraintestinal presentations without enteropathy has only recently become accepted. In this Personal View, we review the range of neurological manifestations of gluten sensitivity and discuss recent advances in the diagnosis and understanding of the pathophysiological mechanisms underlying neurological dysfunction related to gluten sensitivity.

Abstract

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Gluten-free diet and steroid treatment are effective therapy for most patients with collagenous sprue. – Clinical Gastroenterology and Hepatology, 2010

Abstract

BACKGROUND & AIMS: Collagenous sprue (CS) is characterized by the presence of a distinctive band of subepithelial collagen deposition in the small bowel. We evaluated the clinical characteristics, treatments, and outcomes of patients with CS.

METHODS: Thirty patients with CS were identified at the 3 Mayo Clinic sites between 1993 and 2009. Clinical data from medical records were reviewed.

RESULTS: The study cohort was 70% female (age range, 53-91 years). Most patients had severe diarrhea and weight loss. Hospitalization to treat dehydration was necessary in 16 (53%) patients. Associated immune-mediated diseases were noted in 70% of the patients; celiac disease was the most frequent. Other associated diseases were microscopic colitis, hypothyroidism, and autoimmune enteropathy. The median thickness of the layer of subepithelial collagen deposition in the small bowel was 29 mum (20-56.5 mum). Subepithelial collagen deposition in the colon or stomach was noted in 8 patients. A clinical response was observed in 24 (80%) patients after treatment with a combination of a gluten-free diet and immunosuppressive drugs. Histologic improvement was confirmed in 9 patients, with complete remission in 5. Two patients died (1 of complications of CS and 1 of another illness).

CONCLUSIONS: Most patients with CS are treated effectively with a combination of gluten-free diet and steroids. CS is often associated with collagen deposition or chronic inflammation in other segments of the gastrointestinal tract as well as other immune-mediated disorders.

Gluten sensitivity in multiple sclerosis: experimental myth or clinical truth? – Annals of the New York Academy of Sciences, 2010

Abstract

Patients with neurological disease of unknown etiology sometimes present with antigliadin and antitissue transglutaminase antibodies. The association between these antibodies and multiple sclerosis has been previously suggested. The purpose of this study was to determine the prevalence of these antibodies in multiple sclerosis patients. We determined the level of serum immunoglobulin A and immunoglobulin G antigliadin and antitissue transglutaminase antibodies in 98 patients with multiple sclerosis. We found a highly significant increase in titers of immunoglobulin G antibodies against gliadin and tissue transglutaminase in the multiple sclerosis patients. Seven patients had a positive IgG AGA, whereas only 2 controls presented positive titers (P = 0.03). Four patients had positive IgG anti-tTG while all the controls tested negative (P = 0.02). However, immunoglobulin A antibodies against gliadin and tissue transglutaminase were not statistically higher in the multiple sclerosis group in comparison to the control group. Our findings support the associations between antibodies against gliadin and tissue transglutaminase to multiple sclerosis. The specific role of these antibodies in the pathogenesis of multiple sclerosis remains uncertain and requires additional research. A gluten free diet should be considered in specific cases of patients who present with gluten antibodies.

Novel immune response to gluten in individuals with schizophrenia. – Schizophrenia Research, 2010

Abstract

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.

Abstract

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Gluten sensitivity presenting as myoclonic epilepsy with cerebellar syndrome. – Movement Disorders, 2009

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Gluten encephalopathy with psychiatric onset – Clinical Practice and Epidemiology in Mental Health, 2009

Abstract

ABSTRACT: Many cases of coeliac disease, a gastrointestinal autoimmune disorder caused by sensitivity to gluten, can remain in a subclinical stage or undiagnosed. In a significant proportion of cases (10-15%) gluten intolerance can be associated with central or peripheral nervous system and psychiatric disorders.A 38-year-old man was admitted as to our department an inpatient for worsening anxiety symptoms and behavioural alterations. After the addition of second generation antipsychotic to the therapeutic regimen, the patient presented neuromotor impairment with high fever, sopor, leukocytosis, raised rhabdomyolysis-related indicators. Neuroleptic malignant syndrome was strongly suspected. After worsening of his neuropsychiatric conditions, with the onset of a frontal cognitive deficit, bradykinesia and difficulty walking, dysphagia, anorexia and hypoferraemic anaemia, SPET revealed a reduction of cerebral perfusion and ENeG results were compatible with a mainly motor polyneuropathy. Extensive laboratory investigations gave positive results for anti-gliadin antibodies, and an appropriate diet led to a progressive remission of the encephalopathy.

Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis. – BMC Gastroenterology, 2009

Abstract

BACKGROUND: Gluten sensitive enteropathy (GSE) is an autoimmune enteropathy triggered by the ingestion of gluten-containing grains in susceptible individuals. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of GSE. The aim of this study was to determine the prevalence of gluten sensitivity enteropathy (GSE) in a large group of patients with RAS and assess the efficacy of gluten free diet (GFD) on the improvement of aphthous lesions in those who were diagnosed with GSE.

METHODS: Two hundred and forty seven patients with RAS were included. The patients had at least three aphthous attacks per year. Patients were screened by IgA anti-endomysial antibody (EMA), IgA anti tissue transglutaminase (TTG) and serum IgA level. Those with a positive serology underwent endoscopic biopsies of the duodenal mucosa and patients with negative serology were excluded. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. For patients with GSE, gluten free diet was recommended.

RESULTS: Six out of 247 RAS patients had positive TTG test alone, and one had positive EMA and TTG. All 7 patients with positive serologic tests underwent duodenal biopsies. Histological findings were compatible with GSE in all of them (Marsh I in four patients, Marsh II in two patients and Marsh IIIB in one another.). The mean age of GSE patients was 27.42 +/- 10.56 (range, 13 to 40) years old. They were suffering from RAS for an average duration of 4.5 years. All of the 7 GSE patients had not responded to the routine anti-aphthae medications, including topical corticosteroids, tetracycline and colchicine. Four patients who adhered to a strict gluten-free diet showed noticeable improvement in their aphthous lesions over a period of 6 months.

CONCLUSION: A significant minority (e.g. 2.83%) of RAS patients have GSE. This could be compared with the 0.9% prevalence of GSE in the general population of Iran. This study suggests that evaluation for celiac disease is appropriate in patients with RAS. Additionally, the unresponsiveness to conventional anti-aphthae treatment could be an additional risk indicator.

Abstract

Hypothesis: Gluten causes symptoms, in both celiac disease and non-celiac gluten-sensitivity, by its adverse actions on the nervous system. Many celiac patients experience neurological symptoms, frequently associated with malfunction of the autonomic nervous system. These neurological symptoms can present in celiac patients who are well nourished. The crucial point, however, is that gluten-sensitivity can also be associated with neurological symptoms in patients who do not have any mucosal gut damage (that is, without celiac disease). Gluten can cause neurological harm through a combination of cross reacting antibodies, immune complex disease and direct toxicity. These nervous system affects include: dysregulation of the autonomic nervous system, cerebella ataxia, hypotonia, developmental delay, learning disorders, depression, migraine, and headache. If gluten is the putative harmful agent, then there is no requirement to invoke gut damage and nutritional deficiency to explain the myriad of the symptoms experienced by sufferers of celiac disease and gluten-sensitivity. This is called “The Gluten Syndrome”.

Abstract

BACKGROUND: Coeliac disease is more frequent in IgA nephropathy (IgAN) patients compared to the healthy population. Several hypotheses postulate that food antigens like gluten may be involved in the onset of IgAN.

METHODS: In this study, we used a recently developed mucosal patch technique to evaluate the rectal mucosal inflammatory reaction to gluten in patients with IgAN (n = 27) compared to healthy subjects (n = 18). The rectal mucosal production of nitric oxide (NO) and release of myeloperoxidase (MPO) and eosinophil cationic protein (ECP) were measured. Serum samples were analysed for IgA and IgG antigliadin antibodies (AGA), IgA antibodies against tissue transglutaminase and IgA endomysium antibodies.

RESULTS: Gluten reactivity, defined as increase in MPO and/or NO after gluten exposure, was observed in 8 of 27 IgAN patients. The prevalence of HLA-DQ2 and DQ8 was not increased among gluten-sensitive patients, and the total prevalence among IgAN patients was the same as for the normal population. An elevated serum IgA AGA response was seen in 9 of 27 IgAN patients. The increase in IgA AGA did not correlate with the gluten sensitivity as measured by NO and/or MPO. A specific serum IgG AGA response was seen in one patient only. Antibodies against tissue transglutaminase and endomysium were not observed.

CONCLUSION: It is concluded that approximately one-third of our IgAN patients have a rectal mucosal sensitivity to gluten, but without signs of coeliac disease, and we hypothesize that such sub-clinical inflammation to gluten might be involved in the pathogenesis of IgAN in a subgroup of patients.

Abstract

ABSTRACT: We report the unexpected resolution of longstanding schizophrenic symptoms after starting a low-carbohydrate, ketogenic diet. After a review of the literature, possible reasons for this include the metabolic consequences from the elimination of gluten from the diet, and the modulation of the disease of schizophrenia at the cellular level.

Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity. – Journal of Neurology, Neurosurgery, and Psychiatry, 2009

Abstract

BACKGROUND: Previous studies have associated coeliac disease (CD) and gluten sensitivity (defined as the presence of anti-gliadin antibodies and positive immunogenetics) with cerebellar degeneration and epilepsy with occipital calcifications. Hippocampal sclerosis (HS) in temporal lobe epilepsy (TLE) is a potentially progressive disorder with unknown aetiology; however, autoimmunity has been implicated as one of the possible mechanisms leading to HS. The purpose of this study is to analyze CD-associated antibodies and gluten sensitivity in a well-characterised group of patients with refractory focal epilepsy.

METHODS: We measured anti-gliadin, anti-tissue-transglutaminase and anti-endomysium antibodies, and coeliac-type human leukocyte antigen (DQ2 and DQ8), in 48 consecutive patients with therapy-resistant, localisation-related epilepsy. The patients were categorised into the following three groups on the basis of ictal electro-clinical characteristics and the findings of high resolution MRI: TLE with HS (n = 16), TLE without HS (n = 16) and extratemporal epilepsy (n = 16). Patients with suspected CD or gluten sensitivity underwent duodenal biopsies.

RESULTS: Seven patients in total were gluten sensitive; all of these patients fell in the TLE with HS group. On the other hand, none of the TLE without HS patients or those with extratemporal epilepsy were gluten sensitive (p<0.0002). The results of duodenal biopsies showed that three of the seven gluten-sensitive patients had histological evidence of CD and four had inflammatory changes consistent with early CD without villous atrophy. Four of the patients with gluten sensitivity had evidence of dual pathology (HS+another brain lesion), whereas none of the remaining patients did (p<0.0002).

CONCLUSIONS: The present study demonstrates a previously unrecognised link between gluten sensitivity and TLE with HS. This association was very robust in this well-characterised group of patients; thus gluten sensitivity should be added to the list of potential mechanisms leading to intractable epilepsy and HS.

Relapsing acute pancreatitis associated with gluten enteropathy. – Revista Espanola de Enfermedades Digestivas (Spanish Review of Digestive Diseases)

Abstract

OBJECTIVES: To describe the frequency and the clinical and laboratory characteristics of relapsing acute pancreatitis (AP) associated with gluten enteropathy (GE).

PATIENTS AND METHODS: We prospectively examined all acute pancreatitis cases admitted to our Department in 2006. We recorded a total of 185 patients. With recurring forms, 40 (22%) in all, we used a clinical-lab protocol including serologic and genetic markers, and duodenal biopsy to rule out GE.

RESULTS: A total of 34 patients (18%) met clinical-biological criteria for GE (group1), and were compared to the remaining non-GE AP cases (n=161) (group2). Mean age in the GE group was 54 +/- 25 years, slightly younger than group 2 (61 +/- 14) (NS). There was a mild predominance of women (50%) in group 1 versus group 2 (38.5%) (NS). Seven patients in group 1 (20%) had severe AP, as compared to 27 (17%) in group 2 (NS). The presence of cholelithiasis in group 1 involved 6 cases (18%), which was significantly lower than in group 2–72 cases (45%) (p < 0.05). Four patients with GE developed pseudocysts (12%) versus 13 (8%) in group 2 (NS). Tissue transglutaminase (tTG) was elevated only in 3 patients (9%). Nine patients (34%) were DQ2 (+) and 4 (12%) DQ8 (+); the rest (54%) were all negative for both markers. From an endoscopic perspective there was diffuse duodenitis in 32 patients (95%). Duodenal biopsies revealed villous atrophy (Marsh 3) in 2 patients (6%); submucosal inflammatory infiltration (Marsh 2) in 10 (29.4%); increased intraepithelial lymphocytes (Marsh 1) in 8 cases (23.5%), and normal mucosa (Marsh 0) in 14 patients (41.2%). Response to GFD after 1 year was excellent in 30 patients (88%).

CONCLUSIONS: Relapsing AP with GE represents a relatively common association that is indistinguishable from other APs from a clinical-evolutive standpoint, except for a lower presence of cholelithiasis (p < 0.05). A specific diagnostic protocol is much needed in the identification of these patients since GFD is the only effective therapy to prevent new AP events from developing.

Autoantibodies in gluten ataxia recognize a novel neuronal transglutaminase. – Annals of Neurology, 2008

Abstract

OBJECTIVE: Gluten sensitivity typically presents as celiac disease, a chronic, autoimmune-mediated, small-intestinal disorder. Neurological disorders occur with a frequency of up to 10% in these patients. However, neurological dysfunction can also be the sole presenting feature of gluten sensitivity. Development of autoimmunity directed toward different members of the transglutaminase gene family could offer an explanation for the diversity in manifestations of gluten sensitivity. We have identified a novel neuronal transglutaminase isozyme and investigated whether this enzyme is the target of the immune response in patients with neurological dysfunction.

METHODS: Using recombinant human transglutaminases, we developed enzyme-linked immunosorbent assays and inhibition assays to analyze serum samples of patients with gluten-sensitive gastrointestinal and neurological disorders, and various control groups including unrelated inherited or immune conditions for the presence and specificity of autoantibodies.

RESULTS: Whereas the development of anti-transglutaminase 2 IgA is linked with gastrointestinal disease, an anti-transglutaminase 6 IgG and IgA response is prevalent in gluten ataxia, independent of intestinal involvement. Such antibodies are absent in ataxia of defined genetic origin or in healthy individuals. Inhibition studies showed that in those patients with ataxia and enteropathy, separate antibody populations react with the two different transglutaminase isozymes. Furthermore, postmortem analysis of brain tissue showed cerebellar IgA deposits that contained transglutaminase 6.

INTERPRETATION: Antibodies against transglutaminase 6 can serve as a marker in addition to human leukocyte antigen type and detection of anti-gliadin and anti-transglutaminase 2 antibodies to identify a subgroup of patients with gluten sensitivity who may be at risk for development of neurological disease.

Abstract

Gluten ataxia is an immune-mediated disease triggered by the ingestion of gluten in genetically susceptible individuals. It should be considered in the differential diagnosis of all patients with idiopathic sporadic ataxia. Early diagnosis and treatment with a gluten free diet can improve ataxia and prevent its progression. Readily available and sensitive markers of gluten ataxia include antigliadin antibodies. IgA deposits against TG2 in the small bowel and at extraintestinal sites are proving to be additional reliable and perhaps more specific markers of the whole spectrum of gluten sensitivity. They may also hold the key to its pathogenesis.

Neuromyelitis optica in patients with gluten sensitivity associated with antibodies to aquaporin-4. – Journal of Neurology, Neurosurgery, and Psychiatry, 2008

Abstract

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