IgG Antigliadin Research Articles

Investigating the Role of Gluten Sensitivity in the Etiology of Autism Spectrum Disorder.

&lt;b&gt;Background and Objective:&lt;/b&gt; Autism Spectrum Disorder (ASD) is a range of neurodevelopmental disabilities that lack a clear etiology. To date, studies investigating the role of immune reactivity to gluten in ASD have been inconsistent. This study aimed to compare levels of gluten reactivity markers in 319 ASD patients to 172 of their unaffected siblings and 322 of unrelated healthy controls (UHC). &lt;b&gt;Materials and Methods:&lt;/b&gt; Patients younger than 12 years old diagnosed with ASD via experienced child psychiatrists and neuro-pediatricians were recruited and gluten reactivity markers and gastrointestinal (GI) complaints commonly found in children with ASD were also investigated. Serum levels of anti-gluten and anti-tissue transglutaminase IgA (anti-TTG IgA) were measured via ELISA. &lt;b&gt;Results:&lt;/b&gt; No significant differences were detected in IgA levels and IgG levels for anti-TTG among all groups (p<0.05). The anti-gliadin IgG levels were significantly higher in ASD patients and their siblings compared to the UHC group (p<0.05). Also, those IgG levels were not associated with any GI complaints or Electroencephalogram (EEG) abnormalities (p>0.05). &lt;b&gt;Conclusion:&lt;/b&gt; The data suggested gluten sensitivity has no role in ASD pathophysiology or its comorbid symptoms.

The use of anti-transglutaminase and anti-gliadin antibodies to compare the effect of gluten active and gluten-free diet patients suffering from celiac disease in child and adult

Celiac disease is an autoimmune disorder triggered by the ingestion of gluten in genetically susceptible individuals. The current study aimed to compare the levels of these antibodies in celiac disease patients on active gluten-containing diets and those on gluten-free diets to demonstrate the ability to get rid of Celiac Disease by Gluten-Free Diet. The study involved 100 participants, divided into 60 CD patients and 40 controls, where all participant match in age and gender. The patient group was further divided into two subgroups 40 active celiac and 20 GFD. Blood samples were obtained from all participants, and levels of anti-tTG and anti-gliadin antibodies were using Enzyme-Linked Immunosorbent Assay (ELISA) technology. The results showed The F test indicated a significant difference in the levels of anti-tTG and anti-gliadin antibodies between the active group (G1) and the diet group (G2) in comparison to the control group (G3), with a p-value less than 0.001. Upon conducting a deeper analysis using the least significant difference (LSD) on on anti-tTG IgA and IgG indicate that there are no significant differences between the patient groups G1 and G2, as evidenced by p-values of 0.120 for IgA. However, a significant difference was observed between G1 and G2 for IgG, with a p-value of 0.018. When comparing G1 with G3, and G2 with G3, significant differences were observed, with p-values less than 0.001. In the case of anti-gliadin IgA and IgG, the LSD test revealed a highly significant difference between G1 and G2, as indicated by a p-value less than 0.001. However, no significant differences were found between G1 and G3, with p-values of 0.499 for IgA and 0.110 for IgG. A highly significant difference was none the less observed between G2 and G3, with a p-value less than 0.001.In conclusion, This study highlights the importance of dietary adherence in celiac disease management. Patients on gluten-free diets had significantly lower levels of anti-TG and anti-gliadin antibodies, indicating better control of the autoimmune response. Monitoring these antibody levels can be a valuable tool in assessing the effectiveness of dietary interventions in celiac disease patients.

A22 INVESTIGATING THE EFFECTS OF DIET TRIGGER DISCLOSURE ON BEHAVIOUR IN IRRITABLE BOWEL SYNDROME (IBS) PATIENTS WITH PERCEIVED GLUTEN SENSITIVITY

Abstract Background Patients with self-perceived gluten sensitivity often undergo double-blinded, placebo-controlled (DBPC) challenge studies to determine whether gluten or wheat trigger their symptoms. However, it is unknown whether the result disclosure impacts patients’ beliefs and dietary choices. Aims To evaluate the impact of disclosing results of DBPC challenge with gluten and wheat on beliefs and dietary choices in IBS patients who adopt a gluten-free diet (GFD). Methods We conducted a DBPC crossover trial in 28 adult IBS patients (Rome IV) who previously reported improvement of symptoms while on a GFD. Patients were on a GFD throughout the study and were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low-FODMAP cereal bars, followed by 2-week washouts. Genetic predisposition to celiac disease and anti-gliadin IgG (AGA) were assessed. At least 6 months after the study completion, patients were contacted to assess their current diet, dietary beliefs, and symptoms prior to disclosing their study results. We assessed the same outcomes one month later. Statistical comparisons used paired Wilcoxon signed rank tests. Results The DBPC study showed similar proportions of participants reacting to wheat, gluten, and nocebo challenge, with greater symptoms after wheat compared to baseline (P&amp;lt;0.05). AGA IgG were present in 8% (2/25) and celiac disease-related genes in 80% (20/25) of patients. Out of 28 participants, 26 completed the pre-disclosure and 25 completed post-disclosure follow-up. All participants (N=26) believed that at least one challenge triggered their symptoms: whole wheat N=22, pure gluten N=23, nocebo N=2. Prior to disclosure, 17 participants continued while 9 abandoned the GFD; none changed their diet post-disclosure. Reasons to stay on the GFD included belief in its efficacy (N=16) and better quality of life (N=15), while reasons for abandoning included difficulty to adhere to the GFD and its cost (N=6) and losing belief in its efficacy (N=3). IBS symptoms did not change pre- vs. post-disclosure. Participants not reacting to wheat or gluten challenge expressed slightly lower median belief in GFD efficacy pre- vs. post-disclosure (80%, IQR [64%, 97%] vs 71%, IQR [48%, 78%]; P=0.03; Figure 1). Those worsening after wheat or gluten did not change their beliefs. Conclusions Although most IBS patients with self-perceived gluten sensitivity had celiac disease predisposition, only some reacted to gluten or wheat. Furthermore, after disclosing the study results, all participants maintained their dietary habits avoiding gluten, thus suggestive of strong central mechanisms underlying their symptoms. Figure 1. Belief in GFD efficacy pre- vs. post-disclosure of study results. Funding Agencies CIHRSociety for the Study of Celiac Disease, Nestle

Celiac disease and H. pylori existence in the adult population and its effects on anemia incidence.

Anemia is a common extraintestinal symptom of celiac disease; however, inflammation and Helicobacter pylori (HP) infection can also induce anemia. Anemia is associated with both H. pylori infection and celiac disease, which can significantly impact public health. In our study, we aimed to determine the impact of H. pylori infection on anemia in celiac disease adults. In this study, 150 celiac disease patients with endoscopy results were retrospectively analyzed. Patients' gender, age, Oberhuber-Marsh scores, presence of H. pylori, presence of anemia, serum tissue transglutaminase (TTG), immunoglobulin (Ig) A and IgG levels, anti-gliadin antibody (AGA) IgA and IgG levels, Endomysial Antibody (EMA) IgA and IgG levels, serum hemoglobin, C-reactive peptide (CRP), ferritin, vitamin B12, folate, total protein, and albumin levels, serum neutrophil, monocyte, lymphocyte, eosinophil, and platelet counts, and mean corpuscular volume, mean platelet volume and platelet distribution width variables were examined. The patients were divided into HP-negative and HP-positive groups, and statistical analysis was performed between the two groups. Among all patients, HP infection was seen in 24 (16%) patients. There was no difference between HP-positive and HP-negative groups in terms of gender, age, Marsh scores, serologic test levels, platelet, lymphocyte, neutrophil counts, CRP, vitamin B12, and folate levels. The anemia rate of HP-negative patients was 32.54%, HP-positive patients' rate was found to be significantly higher at 79.17% (p<0.001). The ferritin median of HP-negative patients was 41.49 (1-1441) and 13 (2.4-22) for HP-positive patients (p<0.001). Anemia rates were 6.8-fold higher in HP-positive celiac patients. Celiac disease patients with anemia should have HP infection on their list of possible causes, especially in patients with refractory anemia.

P235 Cerebellar ataxia in primary Sjogren’s syndrome: is gluten sensitivity the answer?

Abstract Background/Aims Cerebellar ataxia is an uncommon neurological complication of Primary Sjogren’s Syndrome (PSS), with case reports being the highest level of evidence available. The underlying disease pathogenesis is unknown, although an immunologically mediated mechanism seems plausible. Gluten sensitivity is common amongst patients with PSS and is a known cause of immune-mediated ataxia (gluten ataxia). We aimed to investigate the presence of ataxia in patients with PSS seen in the joint rheumatology-neurology clinics at our institution, and determine if gluten sensitivity is responsible for cerebellar ataxia in some of these patients. Methods A retrospective review of all patients who attend the rheumatology and joint rheumatology-neurology clinics was conducted. Patient data including patient demographics, the presence of gluten sensitivity-related antibodies (anti-tissue transglutaminase 2, anti-gliadin IgG and IgA, endomysial antibodies, anti-transglutaminase 6 IgG and IgA), were collected. Patients attending the rheumatology clinics with PSS were asked about the presence of any symptoms of unsteadiness. Such patients underwent MR spectroscopy of the cerebellum looking for any evidence of abnormal cerebellar metabolites (N-acetylaspartate-to-creatine (NAA/Cr) ratio &amp;lt;1). Electrophysiology results in the form of nerve conduction studies (NCS) or electromyography (EMG) were also collected. Results We identified 45 patients with symptoms of impaired balance. Not all of the 236 patients with PSS who regularly attend the rheumatology clinics were assessed for any evidence of loss of balance. Nonetheless, at least 45 out of 236 patients (19.1%) complained of balance problems. The majority of these patients were female (41/45, 91.1%) with a mean age of 64.3 years. Thirty-three out of 45 patients with ataxia (73.3%) tested positive for one or more of gluten sensitivity-related antibodies, with IgA TG6 being the most common (17/33 patients, 51.5%). Out of the 33 gluten sensitive patients, 25 had MR spectroscopy of the cerebellum and 17/25 (68%) had an abnormal NAA/Cr ratio. Twenty-two patients had NCS/EMG studies performed, of which 13 (59.1%) had either a sensory-motor neuropathy or sensory ganglionopathy. Conclusion The high prevalence of gluten sensitivity-related autoantibodies, combined with objective evidence of ataxia, suggest that gluten sensitivity may be responsible for the majority of cases of ataxia in PSS. The presence of a neuropathy in some of these patients suggests that sensory ataxia may also be contributing to the impaired balance in some of these patients. There is, however, a cohort of patients with ataxia and PSS who are not gluten sensitive. These patients may well have primary autoimmune cerebellar ataxia (PACA). Whilst a therapeutic response to a gluten free diet in patients with gluten ataxia has already been established, it remains to be seen if those patients with PSS and ataxia who have no evidence of gluten sensitivity may benefit from immunosuppression. Disclosure F. Kon: None. M. Akil: None. R. Kilding: None. K. Kuet: None. P. Shanmugarajah: None. N. Hoggard: None. M. Hadjivassiliou: None.

Patterning Large-Scale Nanostructured Microarrays on Coverslip for Sensitive Plasmonic Detection of Aqueous Gliadin Traces

User-friendly devices for detecting low gliadin content in commercial foods are of extreme importance for people with gluten diseases. With this concern, the present work proposes a rapid and sensitive optical nanostructured microarrays platform for the detection of gliadin using specific anti-gliadin IgG antibodies immobilized on annealed gold nanostructures (AuNPs) obtained after the high annealing process (550 °C) of gold thin films evaporated on commercial glass coverslips. Localized Surface Plasmon Resonance (LSPR) immunosensing of gliadin in the range of 0.1 ppm to 1000 ppm is successfully achieved. In addition, the biofunctionalization protocol was used for gluten screening in five food complex products.

Assessment of Markers of Gut Integrity and Inflammation in Non-Celiac Gluten Sensitivity After a Gluten Free-Diet.

PurposeMarkers for gut integrity and inflammation have received increasing interest as intestinal permeability and innate immune system activation are suggested as possible pathophysiological mechanisms in non-celiac gluten sensitivity (NCGS). We aimed to assess relevant biomarkers in NCGS by analyzing serum levels of gut integrity and permeability markers, pro-inflammatory cytokines and antigliadin IgG in patients with suspected NCGS on a gluten-free diet (GFD), and compare them to serum levels in patients with irritable bowel syndrome (IBS) and healthy controls (HC).Patients and MethodsSerum samples collected from patients with suspected NCGS on a GFD (n=20, 14 women, 21–62 years), IBS (n=20, 16 women, 24–67 years) and HC (n=20, 14 women, 21–54 years) were analyzed. IBS severity scoring system (IBS-SSS) was applied to evaluate gastrointestinal symptoms.ResultsThe IBS-SSS score was higher in subjects with suspected NCGS and IBS patients compared to HC (p<0.0001). No significant differences were found in the serum levels of any of the gut integrity and permeability markers, cytokines or antigliadin IgG antibodies between the three groups. However, positive correlations were observed between claudin-1 and i-FABP, and between claudin-1 and antigliadin IgG antibodies.ConclusionNo differences in serum levels of gut integrity and permeability markers, pro-inflammatory cytokines or antigliadin IgG antibodies were found among patients with suspected NCGS on a GFD, IBS and HC.

Celiac Disease.

Celiac Disease.

Serologic Testing for Celiac Disease in Graves’ Hyperthyroidism: Should We Act Early?

ABSTRACT Background: The general practice is to screen patients with autoimmune thyroid disease for celiac disease (CD); however, optimal timing for CD screening for patients with Graves’Disease (GD) has not been identified yet. The aim of the study was to show whether positive celiac antibodies persist after euthyroidism is achieved. Materials and Methods: Serum samples were collected from 35 patients with GD (23 female and 12 male) who applied to the endocrine outpatient clinic. Patients and healthy controls were screened for CD with IgG and IgA antigliadin antibodies (IgG – AGA and IgA – AGA), IgA endomysial antibody (IgA-EMA) and IgA tissue transglutaminase antibody (IgA anti-tTG). These antibodies were reevaluated when patients were euthyroid under antithyroid therapy. Small intestine biopsy was offered to the patients who remained antibody positive after being euthyroid. Results: Screening 35 patients with GD revealed positive results for IgA-AGA (n = 6/35, 17%), IgG-AGA (n = 9/35, 26%), IgA-EmA (n = 2/35, 6%) and IgA-tTG (n = 2/35, 6%). No patient had multiple antibodies positive. Selective IgA deficiency was not detected in patients and controls. When patients were euthyroid, baseline positive IgA-AGA, IgG-AGA, and IgA-EmA became negative, while positive anti-tTG persisted in two patients. Endoscopic duodenal biopsy showed a normal villi/crypts ratio in these patients. None of the controls had positive antibodies. Conclusion: Due to possibility of false seropositivity of celiac antibodies in patients with Graves’ thyrotoxicosis, one should defer testing for CD until euthyroidism has been achieved.

Serological Tests Assessment in Patients Suspected to have Celiac Disease Attending the Gastroenterology and Hepatology Teaching Hospital in Baghdad

Background: Celiac disease is characterized by small intestinal malabsorption of nutrients after the ingestionof wheat gluten or related proteins from rye and barley, villus atrophy of the small intestinal mucosa, promptclinical and histologic improvement following strict adherence to a gluten-free diet, and relapse when glutenis retaken.Aim of the Study: Evaluation of patients seeking gastroenterology and hepatology teaching hospital/medicalcity/Baghdad with suspected celiac disease regarding serological investigation, histological findings andgenetic testing, to determine sensitivity, specificity, positive predictive value and negative predictive valuefor every test.Patients and Method: The study is a cross sectional descriptive analytic study conducted at the teachinghospital of gastroenterology and hepatology/Baghdad/Iraq during a period from the 1st of February 2018 tothe 1st of April 2019. After thorough history and Clinical examination patients with suspected celiac diseasewere sent for serological investigation (TTG IgA and IgG), (antigliadin IgA and IgG), all patients were sentfor endoscopic examination for duodenal biopsies with subsequent histological assessment. Patients whofailed to be confirmed (positive serology and negative histology or vice versa) were sent either for HLAgenotyping or for IgG Deaminated gliadin peptide. Sensitivity &amp; specificity were measured for each test.Results: A total of 140 suspected celiac disease patients involved in this study. Mean age was 18.9 yearsand ranged from 2 years to 60 years. Male represented 36.4% of the cases while female represented 63.6%.Only 19 patients show positive family history of celiac disease (13.6 %). Regarding associated autoimmunediseases, the majority (111 patients) have no associated diseases (79.3%) while the other patients who haveassociations most of them show positive association with type 1 DM (16.4%).Fifty patients (35.7%) presented with short stature, (25.7%) came with diarrhea. The other symptoms varybetween bloating and distention, unexplained anemia and weight loss. Constipation was seen in one patient.tTG IgA and tTG IgG showed high sensitivity, specificity, positive predictive value and negative predictivevalue while antigliadin antibody failed to show these significant results.Conclusion: The use of serologic markers inceliac is easy, direct, noninvasive and reliableand could be benefit in the diagnosis andmonitoring of the disease. More specifically,both the tTG-IgA/IgG are very good markersin the diagnostis of CD. This study confirmedthe high specificity and sensitivity of tTG, and the low results of AGA, but celiac serology does not replace the biopsy in the diagnosis but is useful as anassistant for diagnosis.

Size-Dependent Phagocytic Uptake and Immunogenicity of Gliadin Nanoparticles.

The main objective of the present study was to investigate the hemo and immune compatibility of gliadin nanoparticles as a function of particle size. Gliadin nanoparticles of different size were prepared using a modified antisolvent nanoprecipitation method. The hemolytic potential of gliadin nanoparticles was evaluated using in vitro hemolysis assay. Phagocytic uptake of gliadin nanoparticles was studied using rat polymorphonuclear (PMN) leukocytes and murine alveolar peritoneal macrophage (J774) cells. In vivo immunogenicity of gliadin nanoparticles was studied following subcutaneous administration in mice. Gliadin nanoparticles were non-hemolytic irrespective of particle size and hence compatible with blood components. In comparison to positive control zymosan, gliadin nanoparticles with a size greater than 406 ± 11 nm showed higher phagocytic uptake in PMN cells, while the uptake was minimal with smaller nanoparticles (127 ± 8 nm). Similar uptake of gliadin nanoparticles was observed in murine alveolar peritoneal macrophages. Anti-gliadin IgG antibody titers subsequent to primary and secondary immunization of gliadin nanoparticles in mice were in the increasing order of 406 ± 11 nm < 848 ± 20 nm < coarse suspension). On the other hand, gliadin nanoparticles of 127 ± 8 nm in size did not elicit immunogenic response. Phagocytosis and immunogenicity of gliadin nanoparticles are strongly influenced by particle size. The results of this study can provide useful information for rational design of protein-based nanomaterials in drug delivery applications.

Serological markers of gluten sensitivity in Border terriers with gall bladder mucocoeles

To evaluate serological markers of gluten sensitivity in conjunction with cholecystokinin measurement in Border terriers with gall bladder mucocoeles. Medical records from two referral hospitals were obtained between 2011 and 2019 to identify Border terriers with gall bladder mucocoeles, non-Border terriers with gall bladder mucocoeles and control Border terriers with non-biliary diseases. Enzyme-linked immunosorbent assays were performed on stored fasted serum samples for anti-gliadin IgG, anti-canine transglutaminase-2-IgA autoantibodies and cholecystokinin. Statistical analysis was performed using the Kruskall-Wallis test to identify differences between the groups. Fifteen Border terriers with gall bladder mucocoeles, 17 non-Border terriers with gall bladder mucocoeles and 14 control Border terriers with non-biliary diseases were recruited. Median transglutaminase-2-IgA autoantibodies in Border terriers with gall bladder mucocoeles was 0.73 (range: 0.18 to 1.67), which was significantly greater than in control Border terriers at 0.41 (0.07 to 1.14). Median cholecystokinin concentration in Border terriers with gall bladder mucocoeles was 13 pg/mL (6 to 45 pg/mL), which was significantly lower than in control Border terriers at 103 pg/mL (9 to 397 pg/mL). There was no difference in the anti-gliadin IgG between these groups. There was no difference observed in the non-Border terriers with gall bladder mucocoeles with either of the other groups. Reduced cholecystokinin and increased transglutaminase-2-IgA autoantibodies was detected in Border terriers with gall bladder mucocoeles; which is in part homologous to gall bladder disease identified in human coeliac disease. The results suggest an immunological disease with impaired cholecystokinin release may be affecting gall bladder motility and possibly contributing to mucocoele formation in Border terriers.

Gluten-Free Diet Reduces Symptoms, Particularly Diarrhea, in Patients With Irritable Bowel Syndrome and Antigliadin IgG

Many patients with irritable bowel syndrome (IBS) perceive that their symptoms are triggered by wheat-containing foods. We assessed symptoms and gastrointestinal transit before and after a gluten-free diet (GFD) in unselected patients with IBS and investigated biomarkers associated with symptoms. We performed a prospective study of 50 patients with IBS (ROME III, all subtypes), with and without serologic reactivity to gluten (antigliadin IgG and IgA), and 25 healthy subjects (controls) at a university hospital in Hamilton, Ontario, Canada, between 2012 and 2016. Gastrointestinal transit, gut symptoms, anxiety, depression, somatization, dietary habits, and microbiota composition were studied before and after 4 weeks of a GFD. HLA-DQ2/DQ8 status was determined. GFD compliance was assessed by a dietitian and by measuring gluten peptides in stool. There was no difference in symptoms among patients at baseline, but after the GFD, patients with antigliadin IgG and IgA reported less diarrhea than patients without these antibodies (P= .03). Compared with baseline, IBS symptoms improved in 18 of 24 patients (75%) with antigliadin IgG and IgA and in 8 of 21 patients (38%) without the antibodies. Although constipation, diarrhea, and abdominal pain were reduced in patients with antigliadin IgG and IgA, only pain decreased in patients without these antibodies. Gastrointestinal transit normalized in a higher proportion of patients with antigliadin IgG and IgA. Anxiety, depression, somatization, and well-being increased in both groups. The presence of antigliadin IgG was associated with overall reductions in symptoms (adjusted odds ratio compared with patients without this antibody, 128.9; 95% CI, 1.16-1427.8; P= .04). Symptoms were reduced even in patients with antigliadin IgG and IgA who reduced gluten intake but were not strictly compliant with the GFD. In controls, a GFD had no effect on gastrointestinal symptoms or gut function. Antigliadin IgG can be used as a biomarker to identify patients with IBS who might have reductions in symptoms, particularly diarrhea, on a GFD. Larger studies are needed to validate these findings. ClinicalTrials.gov: NCT03492333.

Проницаемость кишечника и непереносимость глютена и казеина у детей с расстройствами аутистического спектра

Objective. To analyze correlation between the level of intestinal fatty-acid binding protein (I-FABP) and concentration of serological markers of gluten and casein intolerance in children with autism spectrum disorder (ASD). Patients and methods. This study included 55 children aged between 3 and 15 years diagnosed with ASD. Twenty of them followed a gluten-free diet (GFD). All patients were tested for their serum levels of anti-gliadin IgG, anti-deamidated gliadin peptide IgA, anti-casein IgG, and anti-I-FABP IgG using enzyme-linked immunosorbent assay (ELISA). To exclude selective immunodeficiency, we also measured total IgA level. Statistical analysis was performed using the Statistica 10.0 software. We have constructed a three-dimensional surface using paired samples correlations. Results. The level of I-FABP varied between 1.63 and 209 pg/mL (mean 63.54 ± 48.5 pg/mL); its concentration decreased with age (r = -0,786). Increased levels of anti-gliadin antibodies were observed in 17.1% of children with ASD; 73.5% of patients had elevated levels of anti-casein antibodies; none of participants had anti-I-FABP antibodies. Conclusion. After constructing a multidimensional surface for three parameters, we have found certain correlations between the parameters examined, which reflects the existing relationships between them. We suggest using multidimensional descriptive statistics as the basis for constructing relationship functions in further research. Key words: autism, diet therapy, serological markers, leaky gut syndrome, gluten intolerance

3095 Non-Celiac Gluten Sensitivity (NCGS) Presenting as Laryngopharyngeal Reflux (LPR)

INTRODUCTION: Laryngopharyngeal reflux (LPR) is defined as retrograde passage of stomach contents through the esophagus into the larynx and pharynx. Celiac adhering disease is known to cause more severe reflux, often refractory to anti-secretory medications like proton pump inhibitors (PPI). In those cases, the patient will frequently experience symptom relief by adherence to a gluten free diet (GFD). However, little is known about non-celiac gluten sensitivity (NCGS), and the only commercially available test, Antigliadin (AGA) IgG, is positive in about 60% of patients. We present a case of LPR refractory to anti-secretory medication, low acid diet, and reflux surgery that resolved rapidly on a gluten free diet after diagnosing NCGS. CASE DESCRIPTION/METHODS: A 59 years old woman with PMH of gastric bypass surgery (roux-en-Y), GERD, hypothyroidism, MDD, and migraine presented with symptoms of hoarseness, mucous throat clearing, cough, sour taste, and nocturnal choking/laryngospasm events. Flexible fiberoptic laryngoscopy supported the diagnosis of LPR with classic findings of laryngeal edema, erythema, and inflammatory mucus. Treatment with omeprazole 40 mg BID, ranitidine 300 mg QHS, and aluminum hydroxide/magnesium carbonate failed to resolve her symptoms. Persistent severe acid reflux and strong symptom correlation were confirmed with dual sensor pH impedance while esophageal manometry confirmed hypotonic lower esophageal sphincter pressure. She underwent paraesophageal hernia repair and Dor fundoplication resulting in temporary resolution of symptoms that returned one month postoperatively. Although she was unaware of any gluten intolerance, she was tested for gluten sensitivity. Tissue Transglutaminase (TTG) IgA/IgG and Deamidated Gliadin Peptide (DGP) IgA/IgG were normal, but AGA IgG was elevated (111), suggestive of NCGS. She was instructed to follow a GFD, and within one week, all reflux symptoms had resolved, along with headaches, joint pain, and “foggy” mind. DISCUSSION: The patient had classic signs and symptoms of LPR, responsive to GFD, after NCGS was determined by elevated AGA IgG. NCGS remains the least understood form of gluten sensitivity, unlike its counterparts celiac disease and wheat allergy. By exploring the potential connections between LPR and gluten sensitivity, it becomes apparent that some of these patients have gluten sensitivity as the root cause of their reflux symptoms and laryngeal inflammation. More research is needed to better understand the influential diagnosis of NCGS.

Elevated anti-gliadin IgG antibodies are related to treatment resistance in schizophrenia

Elevated anti-gliadin IgG antibodies are related to treatment resistance in schizophrenia

A study of anti-gliadin antibodies in first-episode patients with schizophrenia among a Chinese population

A recent study suggested that digestion-resistant peptides derived from wheat gluten (mainly gliadin) could induce the secretion of anti-gliadin IgG antibodies in patients with schizophrenia. This research was then designed to replicate this initial finding in 134 drug-naïve patients with first-episode schizophrenia and 160 healthy controls. An enzyme-linked immunosorbent assay was developed in-house with 8 gliadin-derived peptide antigens to test anti-gliadin IgG antibodies in the circulation. The results showed that schizophrenia patients had significantly higher levels of plasma anti-AL2G2 IgG and anti-ABO3a IgG than healthy controls. Based on the specificity of 95%, anti-AL2G2 IgG assay had a sensitivity of 12.7% and anti-ABO3a IgG assay had a sensitivity of 17.2% for anti-ABO3a IgG assay. Increased levels of anti-AL2G2 and anti-ABC3a IgG antibodies were not correlated with total IgG levels in either the patient group or the control group. In conclusion, circulating IgG against AL2G2 and ABO3a may be useful biomarkers for identification of a gluten-sensitive subgroup of schizophrenia in the Chinese population although the present results are rather different from the work performed in a British population.

Beneficial Effects of Human Anti-Interleukin-15 Antibody in Gluten-Sensitive Rhesus Macaques with Celiac Disease.

Overexpression of interleukin-15 (IL-15) is linked with immunopathology of several autoimmune disorders including celiac disease. Here, we utilized an anti-human IL-15 antibody 04H04 (anti-IL-15) to reverse immunopathogenesis of celiac disease. Anti-IL-15 was administered to six gluten-sensitive rhesus macaques with celiac disease characteristics including gluten-sensitive enteropathy (GSE), and the following celiac-related metrics were evaluated: morphology (villous height/crypt depth ratio) of small intestine, counts of intestinal intraepithelial lymphocytes, IFN-γ-producing CD8+ and CD4+ T cells, plasma levels of anti-gliadin and anti-intestinal tissue transglutaminase IgG antibodies, as well as peripheral effector memory (CD3+CD28−CD95+) T cells. Anti-IL-15 treatment reversed the clinically relevant disease endpoints, intraepithelial lymphocyte counts, and villous height/crypt depth ratios within jejunal biopsies to normal levels (P < 0.001). Additionally, intestinal CD8+ and CD4+ T cell IFN-γ production was reduced (P < 0.05). Extra-intestinally, anti-IL-15 treatment reduced peripheral NK cell counts (P < 0.001), but otherwise, non-NK peripheral lymphocytes including effector memory T cells and serum blood chemistry were unaffected. Overall, providing the beneficial disease-modulatory and immunomodulatory effects observed, anti-IL-15 treatment might be considered as a novel therapy to normalize intestinal lymphocyte function in celiac disease patients with GSE.

Markers of gluten intolerance in children with autism spectrum disorders and Down'syndrome

To study serological and genetic markers of gluten intolerance in children and teenagers with autism spectrum disorders (ASD) and Down's syndrome (DS). Thirty-three children with ASD (group 1) and 8 with DS (group 2), aged from 2.5 to 15 years, were examined. There were 27 boys and 6 girls in group1, 5 boys and 3 girls in group 2. Most of the children were on a regular diet and only 4 children with ASD kept gluten-free diet (GFD). Using ELI method antibodies to gliadin IgG (AntiGliadin IgG), antibodies to deamidated peptides of gliadin IgA (AntiDGP IgA), immunoglobulin A (IgA) were identified. Haplotypes HLA-DQ2 and DQ8 were determined using PCR. AntiGliadin IgG were identified in 12.1% (4) patients of group 1, with the exception of patients on GFD in 13.8%, and in 50% patients of group 2. One child with ASD had selective IgA deficiency. Haplotypes predisposing to celiac disease had 41.9% of patients of group 1 and 37.5% of patients of group 2. In ASD, the distribution of genotypes was as follows: DQ2 (64.3%), DQ8 (28.6%), DQ2/DQ8 (7.1%,). In DS, all patients had haplotype DQ2. AntiDGP IgA were not identified in both groups. The predominant form of gluten intolerance in children with ASD and DS is sensitivity to gluten, which can be identified in 40-50% of patients. Celiac disease, an autoimmune form of gluten intolerance, can be diagnosed in single cases, although predisposition to it is identified in 41.9% - 37.5% patients with ASD and DS, respectively. Before the start of GFD, laboratory tests should be made to identify forms of gluten intolerance and the use of GFD.

Transglutaminase 6 antibodies in gluten neuropathy

BackgroundTG6 antibodies have been shown to be a marker of gluten ataxia but their presence in the context of other neurological manifestations of gluten sensitivity has not been explored. We investigated the presence of TG6 antibodies in gluten neuropathy (GN), defined as as an otherwise idiopathic peripheral neuropathy associated with serological markers of gluten sensitivity (one or more of antigliadin IgG and/or IgA, endomysial and transglutaminase-2 antibodies). MethodsThis was a cross-sectional study conducted at the Sheffield Institute of Gluten Related Diseases, Royal Hallamshire Hospital, Sheffield, UK. Blood samples were collected whilst the patients were on a gluten containing diet. Duodenal biopsies were performed to establish the presence of enteropathy. ResultsTwenty-eight patients were recruited (mean age 62.5±13.7 years). Fifteen (53.6%) had sensory ganglionopathy, 12 (42.9%) had symmetrical axonal neuropathy and 1 had mononeuritis multiplex. The prevalence of TG6 antibodies was 14 of 28 (50%) compared to 4% in the healthy population. TG6 antibodies were found in 5/15 (33.3%) patients with sensory ganglionopathy and in 8/12 (66.7%) with symmetrical axonal neuropathy. Twenty-four patients underwent duodenal biopsy 11 (45.8%) of which had enteropathy. The prevalence of TG6 was not significantly different when comparing those with or without enteropathy. ConclusionsWe found a high prevalence of antibodies against TG6 in patients with GN. This suggests that TG6 involvement is not confined to the central nervous system. The role of transglutaminase 6 in peripheral nerve function remains to be determined but TG6 antibodies may be helpful in the diagnosis of GN.