Comparison of six human anti-transglutaminase ELISA-tests in the diagnosis of celiac disease in the Saharawi population

AIM: Celiac disease (CD) is an enteropathic disorder very prevalent in Saharawi people. Our aim was to investigate the diagnostic accuracy of six human tissue transglutaminase (tTG) based ELISA tests in Saharawi CD patients. METHODS: Fifty-two CD patients and 23 controls were selected from the Saharawi refugee camps in Tinduf. CD patients were divided into two groups according to their anti-endomysium (EmA) status: 41 EmA positive and 11 EmA negative. Sera from patients and controls were tested for human tTG using six commercial ELISA kits. We used receiver operating characteristics (ROC) curves and areas under the curve to compare the diagnostic accuracies of the six assays. RESULTS: In general, there are differences in the sensitivity and specificity of the human tTG ELISA assays used. Diagnostic accuracy of tests was significantly improved by adjusting the cut-off thresholds according to ROC plot analysis; the correction of the cut-off with the employment of the ROC curve analysis modifies the decision limit in more than 50% in five of the six kits evaluated. CONCLUSION: Some of the human tTG ELISAs used in this study have a diagnostic accuracy similar to EmA determination for diagnosis of CD in Saharawi people. However, it is necessary to select the assay with a higher sensitivity and specificity, and recalculate the cut-off threshold using samples from the referral population.

Autoantibodies related to ataxia and other central nervous system manifestations of gluten enteropathy

Gluten ataxia and other central nervous system disorders could be linked to gluten enteropathy and related autoantibodies.In this narrative review,we focus on the various neuro-logical manifestations in patients with gluten sensitivity/celiac disease,immunological and autoimmune mechanisms of ataxia in connection to gluten sensitivity and the autoantibodies that could be used as a biomarker for diagnosing and following.We focused on the anti-gliadin antibodies,antibodies to different isoforms of tissue transglutaminase(TG)(anti-TG2,3,and 6 antibodies),anti-glycine receptor antibodies,anti-glutamine acid decarboxylase antibodies,anti-deamidated gliadin peptides antibodies,etc.Most studies found a higher prevalence of these antibodies in patients with gluten sensitivity and neurological dysfunction,presented as different neurological disorders.We also discuss the role of a gluten-free diet on the clinical improvement of patients and also on imaging of these disorders.

Effect of the timing of gluten introduction on the development of celiac disease

Celiac disease(CD) is a permanent auto-immune enteropathy,triggered in genetically predisposed individuals by the ingestion of dietary gluten.Gluten is the alcohol-soluble protein component of the cereals wheat,rye and barley.CD is a multifactorial condition,originating from the interplay of genetic and environmental factors.The necessary environmental trigger is gluten,while the genetic predisposition has been identified in the major histocompatibility complex region on chromosome 6p21,with over 90% of CD patients expressing HLA DQ2 and the remaining celiac patients express DQ8.The fact that only about 4% of DQ2/8positive individuals exposed to gluten develop CD,has led to the recognition that other genetic and environmental factors are also necessary.In the last few years,several epidemiological studies have suggested that the timing of the introduction of gluten,as well as the pattern of breastfeeding,may play an important role in the subsequent development of CD.Here,we present and review the most recent evidences regarding the effect of timing of gluten introduction during weaning,the amount of gluten introduced and simultaneous breastfeeding,on the development of CD.

Role of capsule endoscopy in suspected celiac disease: A European multi-centre study

AIMTo analyze the diagnostic yield (DY), therapeutic impact (TI) and safety of capsule endoscopy (CE).METHODSThis is a multi-centre, observational, analytical, retrospective study. A total of 163 patients with suspicion of celiac disease (CD) (mean age = 46.4 ± 17.3 years, 68.1% women) who underwent CE from 2003 to 2015 were included. Patients were divided into four groups: seronegative CD with atrophy (Group-I, n = 19), seropositive CD without atrophy (Group-II, n = 39), contraindication to gastroscopy (Group-III, n = 6), seronegative CD without atrophy, but with a compatible context (Group-IV, n = 99). DY, TI and the safety of CE were analysed.RESULTSThe overall DY was 54% and the final diagnosis was villous atrophy (n = 65, 39.9%), complicated CD (n = 12, 7.4%) and other enteropathies (n = 11, 6.8%; 8 Crohn’s). DY for groups I to IV was 73.7%, 69.2%, 50% and 44.4%, respectively. Atrophy was located in duodenum in 24 cases (36.9%), diffuse in 19 (29.2%), jejunal in 11 (16.9%), and patchy in 10 cases (15.4%). Factors associated with a greater DY were positive serology (68.3% vs 49.2%, P = 0.034) and older age (P = 0.008). On the other hand, neither sex nor clinical presentation, family background, positive histology or HLA status were associated with DY. CE results changed the therapeutic approach in 71.8% of the cases. Atrophy was associated with a greater TI (92.3% vs 45.3%, P < 0.001) and 81.9% of the patients responded to diet. There was one case of capsule retention (0.6%). Agreement between CE findings and subsequent histology was 100% for diagnosing normal/other conditions, 70% for suspected CD and 50% for complicated CD.CONCLUSIONCE has a high DY in cases of suspicion of CD and it leads to changes in the clinical course of the disease. CE is safe procedure with a high degree of concordance with histology and it helps in the differential diagnosis of CD.

Serologic diagnosis of celiac disease: May it be suitable for adults?

The diagnosis of coeliac disease(CD)in adult patients requires the simultaneous assessment of clinical presentation,serology,and typical histological picture of villous atrophy.However,several years ago,the European Society of Pediatric Gastroenterology,Hepatology,and Nutrition guidelines approved new criteria for the diagnosis in children:Biopsy could be avoided when antitransglutaminase antibody(TGA)values exceed the cut-off of×10 upper limit of normal(ULN)and anti-endomysium antibodies are positive,independently from value.This“no biopsy”approach is a decisive need for pediatric population,allowing to avoid stressful endoscopic procedures in children,if unnecessary.This approach relies on the correlation existing in children between TGA levels and assessment of mucosal atrophy according to Marsh’s classification.Several lines of evidence have shown that patients with villous atrophy have markedly elevated TGA levels.Therefore,we aim to perform a narrative review on the topic in adults.Despite that some studies confirmed that the×10 ULN threshold value has a very good diagnostic performance,several lines of evidence in adults suggest that TGA cut off should be different from that of pediatric population for reaching a good correlation with histological picture.In conclusion,the heterogeneity of study reports as well as some conditions,which may hamper the serological diagnosis of CD(such as seronegative CD and non-celiac villous atrophy)and are much more common in adults than in children,could represent a limitation for the“no biopsy”approach to CD diagnosis in patients outside the pediatric age.

A monocenter retrospective study of serological,histological and genetic characteristics of celiac disease in Northern Central Italy

Objective: To examine the seroprevalence, correlates and characteristics of Celiac disease (CD) in a population sample of a Northern Central Area of Italy, by a monocenter retrospective study. Methods: Between 2006 and 2010, serum samples of 9371 subjects (age range 6 months to 91 years) were screened for tissue transglutaminase IgA antibodies (IgA-tTG) by the Immunologia-Allergologia Unit of AUSL1 Massa-Carrara, an area with a population of approximately 150,000. Endomysial IgA antibodies (EMA), HLA typing and small-bowel biopsy were also performed when indicated. Results: Of the 9371 subjects, 269 (2.87%) had positive antibody tests. The population was divided into several age groups and the highest prevalence (5.63%) was found in the 6 months-3 years group. The prevalence of IgA-tTG positivity was double in females compared to males. All IgA-tTG positive patients that were genotyped carried HLA-DQ2 or DQ8, none was a5 positive only. In positive IgA-tTG sera, levels of IgA-tTG were significantly higher in EMA positive than in EMA negative sera (p in children and in adults. Ninety-five/269 IgA-tTG positive subjects underwent biopsy. IgA-tTG levels were different according to the histological degree of the lesion. When EMA were evaluated in IgA-tTG positive subjects the number of EMA negative sera was significantly higher in adults than in children. Conclusions: In summary, this study provides a monocenter retrospective analysis of serological, histological and genetic parameters of subjects with suspicion of CD in an area of Northern Central Italy from 2006 to 2010.