CD-associated Antibodies Research Articles

Intestinal anti-tissue transglutaminase IgA deposits as a complementary method for the diagnostic evaluation of celiac disease in patients with low-grade histological lesions.

Evaluating the usefulness of intestinal anti-transglutaminase IgA (anti-TG2 IgA) deposits detection as a complementary or decision-supporting tool in the diagnosis of celiac disease (CD) in patients with low degree of enteropathy. Small intestinal biopsies (SIB) were performed from 2008 to 2017 in patients on suspicion of CD (positive CD serology and/or symptoms) referred to our Pediatric Gastroenterology Unit. We determined anti-TG2 IgA deposits by using double immunofluorescence in all the patients in whom Marsh 0 or Marsh 1 was detected in the conventional histological study and in a random selection of patients with clearly positive serology and histological Marsh 2-3 lesion. Seventy-five pediatric patients were split into three groups according to the final diagnosis: (i) 13 children with a Marsh 0 or 1, negative CD serology and final non-CD diagnosis; none presented intestinal anti-TG2 IgA deposits; (ii) 15 potential CD cases (Marsh 0 or 1 and CD-associated antibodies), detecting anti-TG2 IgA deposits in 12; on follow-up, another biopsy performed in 11/15 showed villi atrophy in seven and a Marsh 2 lesion in two of them, patients being finally diagnosed as CD cases; and (iii) 47 children with Marsh 2-3 histological lesion and final CD diagnosis; all of them had intestinal anti-TG2 IgA deposits. Anti-TG2 deposits are a useful complementary tool for CD diagnosis in pediatric population with digestive pathologies suggestive of CD. It is especially helpful in those with low-grade lesion, in which anti-TG2 deposits are predictive of the development of more severe lesions on follow-up.

Intestinal anti-transglutaminase 2 immunoglobulin A deposits in children at risk for coeliac disease (CD): data from the PreventCD study.

In coeliac disease (CD), anti-tissue transglutaminase 2 immunoglobulin (Ig)A antibodies (anti-TG2) are produced and deposited in the intestine. PreventCD (www.preventcd.com) is a European multi-centre study, which investigates the influence of infant nutrition and that of genetic, immunological and other environmental factors on the risk of developing CD. The aim of the current study was to evaluate the appearance of intestinal anti-TG2 deposits in very early intestinal biopsies from at-risk infants and their predictive value for villous atrophy. Sixty-five small bowel biopsies, performed in 62 children, were investigated for the presence of intestinal anti-TG2 extracellular IgA deposits by using double immunofluorescence. The biopsies were performed in the presence of elevated serum levels of CD-associated antibodies and/or symptoms suggesting disease. Deposits of anti-TG2 IgA were present in 53 of 53 CD patients and three of three potential CD patients. In potential CD patients, mucosal deposits showed a patchy distribution characterized by some areas completely negative, whereas active CD patients had uniformly present and evident mucosal deposits. Only one of six patients without CD (negative for serum anti-TG2 and with normal mucosa) had intestinal deposits with a patchy distribution and a weak staining. Two of the 53 CD patients received a definitive diagnosis of CD after a second or third biopsy; mucosal deposits of anti-TG2 IgA were evaluated in all samples. Before developing villous atrophy, both patients had anti-TG2 deposits in normal mucosal architecture, antibodies in one patient being absent in serum. We demonstrated that in CD the intestinal deposits of anti-TG2 are a constant presence and appear very early in the natural history of disease.

Gliadin‐reactive T cells in Italian children from preventCD cohort at high risk of celiac disease

Newborns at high risk of celiac disease (CD) were recruited in Italy in the context of the PreventCD study and closely monitored for CD, from 4months up to a mean age of 8years at follow-up. The aim of our study was to investigate intestinal T-cell reactivity to gliadin at the first clinical and/or serological signs of CD. Gliadin-reactive T-cell lines were generated from intestinal biopsies of 19 HLA-DQ2-or HLA-DQ8-positive children. At biopsy, 11 children had a diagnosis of acute CD, two of potential CD, and six were non-celiac controls. Immune reactivity was evaluated against gliadin and known immunogenic peptides from α-, γ-, or ω-gliadins. The role of deamidation by transglutaminase (tTG) in determining the immunogenicity of gliadin was also investigated. Most of the children with CD (either acute or potential) had an inflammatory response to gliadin. Notably, signs of T-cell reactivity to gliadin were also found in some non-celiac subjects, in which IFN-γ responses occurred mainly when regulatory IL-10 and TGF-β cytokines were blocked. Interestingly, PreventCD children reacted to gliadin peptides found active in adult CD patients, and tTG deamidation markedly enhanced gliadin recognition. T cells reactive to gliadin can be detected in the intestine of children at high risk of developing CD, in some cases also in the presence of a normal mucosa and negative CD-associated antibodies. Furthermore, children at a very early stage of CD recognize the same gliadin epitopes that are active in adult CD patients. Tissue transglutaminase strongly enhances gluten T-cell immunogenicity in early CD.

Coeliac Disease-Associated Antibodies in Psoriasis

BackgroundThe possible relationship between psoriasis and coeliac disease (CD) has been attributed to the common pathogenic mechanisms of the two diseases and the presence of antigliadin antibodies in patients has been reported to increase the incidence of CD.ObjectiveThe aim of this report was to study CD-associated antibodies serum antigliadin antibody immunoglobulin (Ig)A, IgG, anti-endomysial antibody IgA and anti-transglutaminase antibody IgA and to demonstrate whether there is an increase in the frequency of those markers of CD in patients with psoriasis.MethodsSerum antigliadin antibody IgG and IgA, antiendomysial antibody IgA and anti-transglutaminase antibody IgA were studied in 37 (19 males) patients with psoriasis and 50 (23 males) healthy controls. Upper gastrointestinal endoscopy and duodenal biopsies were performed in patients with at least one positive marker.ResultsAntigliadin IgA was statistically higher in the psoriasis group than in the controls (p<0.05). Serological markers were found positive in 6 patients with psoriasis and 1 person from the control group. Upper gastrointestinal endoscopy was performed in all these persons, with biopsies collected from the duodenum. The diagnosis of CD was reported in only one patient with psoriasis following the pathological examination of the biopsies. Whereas one person of the control group was found to be positive for antigliadin antibody IgA, pathological examination of the duodenal biopsies obtain from this patient were found to be normal.ConclusionAntigliadin IgA prominently increases in patients diagnosed with psoriasis. Patients with psoriasis should be investigated for latent CD and should be followed up.

Sa1345 Increased Duodenal IL12A mRNA Expression in Celiac Disease Patients Might Lead to Increased IL-35 Production

BACKGROUND. Celiac disease (CD) is an autoimmune enteropathy that affects 1% of the general population. The association between CD and other autoimmune disorders is well established and increased prevalence of CD has been found in patients with type 1 diabetes (7%) and autoimmune thyroiditis (2%). Some reports on co-morbidity of CD and alopecia areata (AA), an autoimmune skin disorder that causes hair loss, have shown a variable hair re-growth upon institution of a gluten-free diet. No studies have addressed the association between CD and the different clinical subtypes of AA, which vary in duration and degree of hair loss. The aim of this study was to investigate the prevalence of CD across the phenotypic spectrum of AA using serological screening methods that have high sensitivity and specificity for CD diagnosis. METHODS. Sera obtained through the National Alopecia Areata Registry of the United States from 16 patients with transient AA (AAT), 24 with patchy persistent AA (AAP), 27 with total scalp hair loss (AT) and 32 with complete body hair loss (AU), were screened for CD using a commercial ELISA kit against combined antitissue transglutaminase and anti-deamidated gliadin peptide IgA and IgG antibodies (antitTG/DGP) from INOVA Diagnostics Inc. Titers >20 IU were considered positive and titers >30 IU were considered strongly positive and suggestive of CD. RESULTS. Of 99 samples (females=64, males=35), a total of 9 (9%) patients (all female) were positive for anti-tTG/ DGP antibodies (range 20.4 61.7 IU) and 4% (2 AT, 1 AU and 1 AAP) were strongly positive. By type of presentation, anti-tTG/DGP titers were elevated in 15% AT, 9% AU and 8% AAP patients but in none of AAT patients. CONCLUSIONS. These results demonstrate that AA patients have a higher prevalence of CD-associated antibodies (9%) than the general population (~3%). CD seropositivity is present in the more severe forms of AA, where hair loss is experienced for more than one year and/or results in total loss of hair from the scalp and/or body. Patients with the least severe form of the disease, transient hair loss lasting less than one year, do not appear to have an elevated risk for CD. Screening for CD is recommended in AA for early detection and institution of a gluten-free diet.

The Prevalence of Celiac Disease Among Patients With Nonconstipated Irritable Bowel Syndrome Is Similar to Controls

Guidelines recommend that patients with symptoms of nonconstipated irritable bowel syndrome (NC-IBS) undergo testing for celiac disease (CD). We evaluated the prevalence of CD antibodies, and biopsy confirmed CD among patients with NC-IBS in a large US population. In a study conducted at 4 sites, from 2003 to 2008, we compared data from 492 patients with symptoms of NC-IBS to 458 asymptomatic individuals who underwent colonoscopy examinations for cancer screening or polyp surveillance (controls). All participants provided blood samples for specific and nonspecific CD-associated antibodies. Additionally, patients with IBS were analyzed for complete blood cell counts, metabolic factors, erythrocyte sedimentation rates, and levels of C-reactive protein and thyroid-stimulating hormone. Any subjects found to have CD-associated antibodies were offered esophagogastroduodenoscopy and duodenal biopsy analysis. Of patients with NC-IBS, 7.3% had abnormal results for CD-associated antibodies, compared with 4.8% of controls (adjusted odds ratio, 1.49; 95% confidence interval: 0.76-2.90; P=.25). Within the NC-IBS group, 6.51% had antibodies against gliadin, 1.22% against tissue transglutaminase, and 0.61% against endomysium (P>.05 vs controls for all antibodies tested). CD was confirmed in 0.41% of patients in the NC-IBS group and 0.44% of controls (P>.99). Although CD-associated antibodies are relatively common, the prevalence of CD among patients with NC-IBS is similar to that among controls in a large US population. These findings challenge recommendations to routinely screen patients with NC-IBS for CD. More than 7% of patients with NC-IBS had CD-associated antibodies, suggesting that gluten sensitivity might mediate IBS symptoms; further studies are needed.

Celiac disease‐associated antibodies in patients with psoriasis and correlation with HLA Cw6

Etiopathology of psoriasis is not completely understood. Patients with psoriasis show elevated sensitivity to gluten. The aim of this study was to see the expression of celiac disease (CD)-associated antibodies gliadin IgA, gliadin IgG, and tissue transglutaminase IgA, and their correlation with HLA Cw6 in patients with psoriasis. The study comprised 56 patients with psoriasis and 60 healthy controls (HC). The levels of antibodies were detected by using ELISA technique and HLA Cw6 typing was carried out by microcytotoxicity method. HLA Cw6 was significantly expressed in psoriasis cases when compared with HC (P<0.05). CD-associated antibodies gliadin IgA/IgG and tissue transglutaminase IgA were significantly higher in the serum of patient with psoriasis when compared with HC (P<0.05, <0.05, and 0.01, respectively). Serum anti tissue transglutaminase IgA (anti tTG IgA) was significantly higher in females when compared with males and expressed more in elderly patients. There was a significant positive correlation among the antibodies (anti gliadin IgA with anti gliadin IgG: r=0.67, P<0.05; anti gliadin IgA with anti tTG IgA: r=0.45, P<0.05, anti gliadin IgG with anti tTG IgA: r=0.26, P<0.05, respectively), whereas insignificant with HLA Cw6. Our study concludes that latent CD or CD-associated antibodies were present in patients with psoriasis and also concludes that HLA Cw6 has no association with expression of these antibodies in patients with psoriasis.

Serum and Intestinal Celiac Disease–associated Antibodies in Children With Celiac Disease Younger Than 2 Years of Age

In children younger than 2 years of age, a diagnosis of celiac disease (CD) is difficult to make because anti-endomysium (anti-EMA)/anti-tissue transglutaminase 2 (anti-TG2) antibodies are less sensitive than in older children. The aim of our study was to evaluate how many children younger than 2 years of age and diagnosed with CD, were negative for serum anti-TG2 antibodies and to test the hypothesis that in these patients, TG2-specific IgA deposits could instead be present at mucosal level. A total of 104 children younger than 2 years of age and 179 children older than 2 years, all of whom had been diagnosed with CD, were investigated for serum CD-associated antibodies (anti-gliadin [AGA] IgA and IgG, EMA-IgA, anti-TG2-IgA). The presence of intestinal anti-TG2 extracellular IgA deposits was searched by using double immunofluorescence in 56 of the patients younger than 2 years of age and in 40 of those who were older than 2 years. In children with CD who were younger than 2 years of age, high levels of AGA-IgA were found in 93/104 (89%) and 98/104 (94%) were found of have high levels of AGA-IgG. In children older than the age of 2 years with CD, 120/179 (67%) had high levels of AGA-IgA and 151/179 (84%) had high levels of AGA-IgG. Serum EMA were present in 92/104 (88%) in the younger group and in 176/179 (98%) of the older group. Ninety-one of 104 children (87%) younger and 172/179 (96%) older than 2 years showed high serum levels of anti-TG2. Finally, 41/56 (73%) children younger than 2 years and all of the 40 children (100%) older than 2 years of age showed mucosal anti-TG2-IgA deposits. EMA and anti-TG2-antibody measurements show higher sensitivity for the diagnosis of CD in children older than 2 years compared with younger children. The search for mucosal deposits of anti-TG2-IgA does not improve the diagnostic performance.

Hippocampal sclerosis in refractory temporal lobe epilepsy is associated with gluten sensitivity

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...

Orally Based Diagnosis of Celiac Disease: Current Perspectives

Celiac disease (CD) is a lifelong immune-mediated disorder caused by the ingestion of wheat gluten in genetically susceptible persons. Most cases of CD are atypical and remain undiagnosed, which exposes the individuals to the risk of life-threatening complications. Serologic endomysial and tissue transglutaminase antibody tests are used to screen at-risk individuals, although a firm diagnosis requires demonstration of characteristic histopathologic findings in the small-intestinal mucosa. A gluten challenge, with a repeat biopsy to demonstrate recurrence of histopathologic changes in the intestinal mucosa after the re-introduction of gluten, is considered for those persons in whom diagnosis remains in doubt. In this paper, we review studies that evaluated: (1) the possibility of using oral mucosa for the initial diagnosis of CD or for local gluten challenge; and (2) the possibility of using salivary CD-associated antibodies as screening tests. Our review shows that orally based diagnosis of CD is attractive and promising, although additional evaluations with standardized collection and analysis methods are needed. There is some evidence of a dissociation between systemic and oral mucosal immune responses in CD. The hypothesis that gluten could stimulate naive lymphocytes directly in the oral cavity would have important implications for the understanding, diagnosis, and management of CD.

Celiac disease autoantibodies in severe autoimmune liver disease and the effect of liver transplantation.

Celiac disease (CD) is associated with primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune hepatitis. We investigated the following: (i) the prevalence of tissue transglutaminase antibodies (tTGAs) and endomysial antibodies (EMAs) in end-stage autoimmune liver disease (ESALD), (ii) the correlation among auto-antibodies and the human leucocyte antigen (HLA) haplotype, and (iii) the effect of liver transplantation on antibody kinetics. Pretransplantation sera from 488 patients (310 with ESALD, and 178 with non-autoimmune disease) were tested for tTGAs. Positive samples were also tested for EMAs, and retested 6-12 and > or = 24 months post-transplantation. Results were correlated with the HLA type of the recipient. Serological evidence of CD was found in 3% (ESALD) vs. 0.6% (non-autoimmune) of the patients (five-fold increased risk in ESALD). The prevalence of tTGAs (14.2 vs. 5.4%, P=0.0001) and EMAs (4.3 vs. 0.78%, P=0.01) was significantly higher in patients with the HLA-DQ2 or HLA-DQ8 haplotypes. tTGAs and EMAs normalized in 94 and 100%, respectively, without gluten exclusion post-transplantation. Post-transplantation, of the five patients with symptoms of 'classical' CD, three improved. Intestinal lymphoma was diagnosed in another two cases with clinically 'silent' CD. Patients with ESALD, especially those who are HLA-DQ2 or HLA-DQ8 positive had a high prevalence of CD-associated antibodies. Both tTGAs and EMAs decreased post-transplantation without gluten withdrawal. Immunosuppression may improve symptoms of CD, but might not prevent progression to intestinal lymphoma.

Simultaneous triple organ specific autoantibody profiling in adult patients with type 1 diabetes mellitus and their first-degree relatives

We aimed to document prevalence and clinical presentations of seropositivities for glutamate decarboxylase (GAD)-antibody, celiac's disease (CD) and autoimmune thyroiditis (AIT) in adult patients with type 1 diabetes mellitus (T1DM), and their first-degree relatives. Sixty-five patients with T1DM, 124 first-degree relatives and 65 healthy controls were screened for GAD-antibody, anti-thyroid peroxidase (ATPO), anti-thyroid stimulating hormone receptor (TSHR), anti-tissue transglutaminase and anti-gliadin antibodies in a matched case-control study. Prevalence of more than one seropositivity for CD-associated antibodies in T1DM-group is 6.0 times increased, compared with controls (p < 0.05). ATPO seropositivity is 5.3 times increased in T1DM group (p < 0.05), but TSHR antibody is comparable with controls (p > 0.05). Seropositivities for T1DM, AIT and CD are 4.3, 1.9 and 2.4 times more prevalent among first-degree relatives respectively, compared with controls (p < 0.05). Pathologically confirmed cases with CD among first-degree relatives were all identified at screening. In contrast, all of pathologically confirmed cases with CD in T1DM group, were either previously diagnosed or symptomatic at time of screening. In the group of patients with T1DM, 31% of seropositive cases for anti-ATPO were clinically latent for AIT, and 74% of ATPO (+) cases were identified at current screening study. Sixty-four per cent of ATPO (+) first-degree relatives were clinically latent for AIT, and 54% were identified at screening. Type 1 diabetes mellitus, CD and AIT represent a significant overlap in an adult population with already-diagnosed T1DM and their first-degree relatives. With regard to clinical presentations, CD was less likely to be clinically silent than AIT among patients with T1DM.

Celiac disease-related antibodies in an epilepsy cohort and matched reference population

Celiac disease (CD) is a common immunologically mediated enteropathic condition manifesting in genetically predisposed individuals after exposure to wheat gluten. CD may be associated with a number of neurological disorders, and the prevalence of epilepsy is reported to be increased in patients with CD. We studied the prevalence of CD-associated antibodies in a cohort of 968 patients with epilepsy and in a population-based reference group of 584 subjects. There was no difference in the prevalence of IgA and IgG class antigliadin antibodies (AGAbA and AGAbG, respectively), endomysial antibodies (EMA), and tissue transglutaminase antibodies (tTGAbA) between patients with epilepsy and the control population. This suggests the presence of CD to be the same in patients with epilepsy and the reference population. However, AGAbA was more prevalent in patients with primary generalized epilepsy (19.6%) than in the reference population (10.6%, relative risk 1.8, 95% confidence interval 1.1–3.0, P = 0.012).

Coeliac disease-associated antibodies correlate with psoriasis activity

Antigliadin antibodies (AGA) have been reported in patients with psoriasis. To determine if AGA and other coeliac disease (CD)-associated antibodies correlate with clinical features and activity in patients with psoriasis. Patients with psoriasis (n = 130) were investigated for serum IgG and IgA AGA, IgA antitransglutaminase antibody and IgA antiendomysial antibody. Disease characteristics and associated bowel and joint symptoms were determined. All patients were invited to undertake endoscopy with duodenal biopsy. A significantly higher proportion of patients with elevated CD-associated antibody levels was currently on or had previously required systemic immunosuppressants (methotrexate, ciclosporin or etretinate; P = 0.04) or psoralen plus ultraviolet A phototherapy (P = 0.03). One case of CD was diagnosed. The presence of CD-associated antibodies in psoriasis patients correlates with greater disease activity.

Celiac disease-like abnormalities in a subgroup of patients with irritable bowel syndrome

Abdominal symptoms in the absence of mucosal abnormalities are features of both the irritable bowel syndrome (IBS) and latent/potential celiac disease (cd). To identify a possible subgroup of IBS patients with latent/potential cd, surrogate markers of cd were investigated in IBS patients. IBS patients suffering from diarrhea (n = 102), and patients with active cd (n = 10), treated cd (n = 26), and latent cd (n = 5) were included in the study. We measured serum immunoglobulin (Ig) A against gliadin and tissue-transglutaminase, and IgA and IgM against gliadin, tissue-transglutaminase (intestinal cd-associated antibodies), and the dietary proteins beta-lactoglobulin and ovalbumin in duodenal aspirate by enzyme-linked immunosorbent assay. Intraepithelial lymphocytes (IELs) were counted in histology sections, and the expression of HLA-DQ2 (A1*0501/B1*0201) was investigated by polymerase chain reaction. In 26 IBS patients, the effect of 6 months of gluten withdrawal was examined. Most cd patients expressed HLA-DQ2 and had increased intestinal cd-associated antibodies, whereas cd-associated serum IgA and IEL counts were increased in active cd in contrast to treated or latent cd. In IBS patients, 35% were HLA-DQ2-positive, 23% had increased IEL counts, and 0% and 30% had increased cd-associated antibodies in serum and duodenal aspirate, respectively. Furthermore, stool frequency and intestinal IgA decreased significantly under a gluten-free diet in the subgroups of HLA-DQ2-positive and intestinal antibody-positive IBS patients when compared with IBS patients without these markers. HLA-DQ2 expression and increased intestinal cd-associated antibodies are markers that can identify latent/potential cd in a subgroup of IBS patients who consequently appear to profit from a gluten-free diet.