HLA-DQ2 and -DQ8 genotypes in celiac and healthy Libyan children

BackgroundFew data are available on the prevalence of celiac disease (CD)-predisposing, HLA-related genes in Arab populations.Aim of the studyTo investigate the distribution of HLA-DQ2 and -DQ8 genotypes in Libyan children with CD and healthy controls.PatientsWe tested 31 Libyan children with CD (22 females and 9 males, median age 9.2 years) and 156 Libyan controls (81 females and 75 males, median age 10.9).MethodsHLA genes were determined on a drop of dried blood by the DQ-CD Typing Plus kit (DiaGene, Palermo, Italy).ResultsThe HLA-DQ pattern of the 31 CD children was: hetero DQ2 (n = 15), DQ2 with homo β2 (10), DQ8 and β2 positive (3), DQ8 (2), and hetero β2 (1). The HLA-DQ pattern of the 156 controls was: hetero DQ2 (n = 36), hetero β2 (30), DQ2–DQ8 negative (23), DQ8 (19), α5 (14), DQ2 with homo β (12), homo β2 (10), DQ8 and β2 positive (7), and DQ2/DQ8 (5).ConclusionsHLA-DQ2 and -DQ8 in CD patients are as common in Libya as in Italy, but the frequency of “high-risk” genotypes is higher in Libyan than Italian patients. The prevalence of HLA-DQ2 and -DQ8 genes in the Libyan general population is higher than in Italy, indicating a strong genetic predisposition to CD.     

Screening for celiac disease in Down＇s syndrome patients revealed cases of subtotal villous atrophy without typical for celiac disease HLA-DQ and tissue transglutaminase antibodies

AIM: To investigate the prevalence of celiac disease (CD) as well as CD marker antibodies and susceptibility HLA-DQ haplotypes in 134 karyotyped Down's syndrome (DS) patients. METHODS: Immunoglobulin A (IgA) and G (IgG) type anti-gliadin antibodies (AGA), IgA type anti-tissue transglutaminase (tTG) antibodies (anti-tTG) with antigen of guinea pig and human source were determined by enzyme-linked immunosorbent assay and endomysium antibodies (EMA) by indirect immunofluoresence test. HLA-DQA1*0501/DQB1*0201 (DQ2) was revealed by polymerase chain reaction. Celiac disease was diagnosed by revised ESPGHAN criteria. RESULTS: 41% of DS patients had AGA, 6.0% IgA anti-tTG with guinea pig antigen, and 3.0 % IgA EMA (all positive for anti-tTG with human tTG). Subtotal villous atrophy was found in 5 out of 9 DS patients who had agreed to small bowel biopsy. One of them had DQA1*0501/DQB1*0201 and anti-tTG and EMA i.e. typical for CD markers (this case also fulfilled the ESPGHAN diagnostic criteria), but other four lacked these markers. Three non-biopsied DS patients had also most probably CD because DQA1*0501/DQB1*0201 and IgA anti-tTG (EMA) were detected. Thus, the prevalence of CD among our DS patients population is 3.0 % (95 % of confidence interval [CI]: 0.1-5.9 %). CONCLUSION: We confirm the increased frequency of CD among DS patients. In addition, we have revealed a subgroup of patients with subtotal villous atrophy but without characteristic for CD immunological and genetic markers. Whether these cases represent CD (with atypical immunopathogenesis) or some other immune enteropathy, requires further investigations.     

Non-responsive celiac disease in children on a gluten free diet

BACKGROUNDNon-responsive celiac disease (NRCD) is defined as the persistence of symptoms in individuals with celiac disease (CeD) despite being on a gluten-free diet (GFD). There is scant literature about NRCD in the pediatric population.AIMTo determine the incidence, clinical characteristics and underlying causes of NRCD in children.METHODSRetrospective cohort study performed at Boston Children’s Hospital (BCH). Children < 18 years diagnosed with CeD by positive serology and duodenal biopsies compatible with Marsh III histology between 2008 and 2012 were identified in the BCH’s Celiac Disease Program database. Medical records were longitudinally reviewed from the time of diagnosis through September 2015. NRCD was defined as persistent symptoms at 6 mo after the initiation of a GFD and causes of NRCD as well as symptom evolution were detailed. The children without symptoms at 6 mo (responders) were compared with the NRCD group. Additionally, presenting signs and symptoms at the time of diagnosis of CeD among the responders and NRCD patients were collected and compared to identify any potential predictors for NRCD at 6 mo of GFD therapy.RESULTSSix hundred and sixteen children were included. Ninety-one (15%) met criteria for NRCD. Most were female (77%). Abdominal pain [odds ratio (OR) 1.8 95% confidence interval (CI) 1.1-2.9], constipation (OR 3.1 95%CI 1.9-4.9) and absence of abdominal distension (OR for abdominal distension 0.4 95%CI 0.1-0.98) at diagnosis were associated with NRCD. NRCD was attributed to a wide variety of diagnoses with gluten exposure (30%) and constipation (20%) being the most common causes. Other causes for NRCD included lactose intolerance (9%), gastroesophageal reflux (8%), functional abdominal pain (7%), irritable bowel syndrome (3%), depression/anxiety (3%), eosinophilic esophagitis (2%), food allergy (1%), eating disorder (1%), gastric ulcer with Helicobacter pylori (1%), lymphocytic colitis (1%), aerophagia (1%) and undetermined (13%). 64% of children with NRCD improved on follow-up.CONCLUSIONNRCD after ≥ 6 mo GFD is frequent among children, especially females, and is associated with initial presenting symptoms of constipation and/or abdominal pain. Gluten exposure is the most frequent cause.     

Contribution of HLA-DQ2/DQ8 haplotypes in type one diabetes patients with/without celiac disease

Background

Based on lack of data on the distribution of the related alleles in the T1D population in Iranian population, we assessed the frequency of HLA DQ2 and DQ8 haplotypes in patients with T1D with/without CD compared to healthy population.

Diagnosis of gluten related disorders: Celiac disease,wheat allergy and non-celiac gluten sensitivity

Cereal crops and cereal consumption have had a vital role in Mankind's history. In the recent years gluten ingestion has been linked with a range of clinical disorders. Gluten-related disorders have gradually emerged as an epidemiologically relevant phenomenon with an estimated global prevalence around 5%. Celiac disease, wheat allergy and non-celiac gluten sensitivity represent different gluten-related disorders. Similar clinical manifestations can be observed in these disorders, yet there are peculiar pathogenetic pathways involved in their development. Celiac disease and wheat allergy have been extensively studied, while non-celiac gluten sensitivity is a relatively novel clinical entity, believed to be closely related to other gastrointestinal functional syndromes. The diagnosis of celiac disease and wheat allergy is based on a combination of findings from the patient's clinical history and specific tests, including serology and duodenal biopsies in case of celiac disease, or laboratory and functional assays for wheat allergy. On the other hand, non-celiac gluten sensitivity is still mainly a diagnosis of exclusion, in the absence of clear-cut diagnostic criteria. A multimodal pragmatic approach combining findings from the clinical history, symptoms, serological and histological tests is required in order to reach an accurate diagnosis. A thorough knowledge of the differences and overlap in clinical presentation among gluten-related disorders, and between them and other gastrointestinal disorders, will help clinicians in the process of differential diagnosis.     

Allele and haplotype frequencies for HLA-DQ in Iranian celiac disease patients

AIM: To assess the distribution of human leukocyte antigen (HLA)-DQ2 and -DQ8 in Iranian celiac disease (CD) patients and compare them to healthy Iranian controls.METHODS: To predict the HLA-DQA1 and -DQB1 genes, we used six previously reported HLA-tagging single nucleotide polymorphism to determine HLA genotypes in 59 Iranian patients with ‘biopsy-confirmed’ CD and in 151 healthy Iranian individuals. To test the transferability of the method, 50 cases and controls were also typed using a commercial kit that identifies individual carriers of DQ2, DQ7 and DQ8 alleles.RESULTS: In this pilot study 97% of CD cases (n = 57) and 58% of controls (n = 87) were carriers of HLA-DQ2 and/or HLA-DQ8 heterodimers, either in the homozygous or heterozygous state. The HLA-DQ pattern of these 57 CD patients: heterozygous DQ2.2 (n = 14) and homozygous DQ2.2 (n = 1), heterozygous DQ2.5 (n = 33) and homozygous DQ2.5 (n = 8), heterozygous DQ8 (n = 13) and homozygous DQ8 (n = 2). Two CD patients were negative for both DQ2 and DQ8 (3%).CONCLUSION: The prevalence of DQ8 in our CD population was higher than that reported in other populations (25.4%). As reported in other populations, our results underline the primary importance of HLA-DQ alleles in the Iranian population’s susceptibility to CD.     

Human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes in celiac,celiac with type 1 diabetic,and celiac suspected pediatric cases

Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten present in wheat, barley, and rye. Gluten along with environmental trigger starts an inflammatory reaction which results in damage to small intestine. Human leukocyte antigen (HLA)-DQA1∗05, -DQB1∗02, and -DQB1∗03:02 are the known risk alleles of CD. The diagnostic method for CD involves serological or intestinal biopsy, but genetic test could be implemented. HLA typing precludes the need for further diagnosis and it has high negative predictive value. The aim of this study was to make aware of HLA molecular typing for celiac disease among local laboratories and healthcare professionals. The prevalence and frequency distribution of HLA-DQ2 and -DQ8 haplotypes in 175 pediatric unrelated healthy controls, celiac patients, and CD with concurrent diabetes mellitus type 1 (DM1) was evaluated. The most common haplotype was DQ2 followed by DQ8. In control group only DQ2 was observed with frequency of 8.5%. In celiac patients 85.7% were DQ2, 11.4% were DQ8, and rest were DQ2/DQ8 (2.8%), and all had CD. In the group of CD with DM1, 31.4% had DQ2, 25% had DQ8, and 34% having both the haplotypes; while only 9 of these patients were suffering from CD. It was concluded that Celiac disease is frequently unrecognized by physicians, in part because of its variable clinical presentation and symptoms. Thus genetic testing for celiac disease could be an additive tool for diagnosis to exclude ambiguity.     

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 ...     

Celiac disease: Alternatives to a gluten free diet

Celiac disease is a chronic inflammatory disorder of the small intestine caused by the ingestion of gluten or related rye and barley proteins. At present, the only available treatment is a strict gluten-exclusion diet. However, recent understanding of the molecular basis for this disorder has improved and enabled the identification of targets for new therapies. This article aims to critically summarize these recent studies.     

The perspective of celiac disease patients on emerging treatment options and non-celiac gluten sensitivity

BackgroundNon-celiac gluten sensitivity (NCGS) and emerging treatment options are hot topics in the celiac disease (CeD) scientific literature. However, very little is known about the perspective on these issues of CeD patients.MethodsWe performed a large patient survey among unselected CeD patients in Switzerland.ResultsA total of 1689 patients were analyzed. 57.5% have previously heard of NCGS. 64.5% believe in the existence of this entity. Regarding a potential influence of NCGS on CeD awareness, 31.7% show a positive and 27.5% a negative perception. Patients with prior use of alternative medicine and women more often have heard of and believe in the existence of NCGS vs. those never having used alternative methods and men, respectively (66.9 vs. 56.9%, p = 0.001 and 78.5 vs. 69.0%, p = 0.001; 60.7 vs. 44.2%, p < 0.001 and 71.0 vs. 60.8%, p = 0.002). Women and patients ≥30 years more often show a negative attitude towards NCGS (32.2% vs. 24.8%, p = 0.024 and 32.2% vs. 24.2%, p = 0.018). With regard to emerging treatment options for CeD, 43.3% have previously heard of novel agents, more women than men (46.0 vs. 38.0%, p = 0.019).ConclusionsPerception of and attitude towards NCGS differ depending on sex, age and prior use of alternative medicine. Knowledge of the progress towards emerging treatment options is currently limited.     

Trends in the presentation of celiac disease

Purpose

Screening studies have revealed that celiac disease is common in the United States; however, there are scant data on the mode of presentation. We analyzed the trends in clinical presentation over the last 52 years in a large cohort of biopsy-proven patients seen in 1 center.

Subjects and methods

Patients (n = 590) were divided into 6 groups based on the year of diagnosis (1952-2004). Groups were compared for trends in age at diagnosis, childhood diagnosis, duration of symptoms, mode of presentation (diarrhea, bone disease, anemia, incidental at esophagogastroduodenoscopy, screening), and presence of malignancy.

Results

Diagnosis was at an older age since 1980 (P = .007), and there was a significant negative linear trend in patients presenting with diarrhea (P<.001) over time and a positive linear trend in asymptomatic patients detected on screening (P<.001). There was a significant negative linear trend in patients with a malignancy (P = .02) and duration of symptoms before diagnosis of celiac disease (P = .001), although only the subgroup without diarrhea had improvement in delay of diagnosis of celiac disease (assessed by a shorter duration of symptoms) (P = .05). Comparison of patients with and without diarrhea showed no significant difference in age (42.9 years vs 43.7 years, P = .59), gender (29.3% M vs 34.6%, P = .59), and presence of childhood disease (8.0% vs 9.8%, P = .43) or malignancies (9.8% vs 8.9%, P = .71).

Conclusion

There is a trend toward fewer patients presenting with symptomatic celiac disease characterized by diarrhea and a significant shift toward more patients presenting as asymptomatic adults detected at screening.     

Five year time course of celiac disease serology during gluten free diet: results of a community based “CD-Watch” program

Background

Little information is available on the effect of a follow-up strategy in celiac disease patients during gluten-free diet.

Aims

To assess 5 year time course of t-transglutaminase antibodies (t-TG) in celiac disease patients enrolled in a community based follow-up program.

Methods

Annual t-TG testing and periodical clinic visit in 2245 patients.

Results

Proportion of patients with negative t-TG progressively increased from 83% to 93% during the 5-year follow-up: poor adherence to gluten-free diet (HR 4.764), long duration of gluten-free diet (HR 0.929) and female gender (HR 1.472) were independently associated with serological outcome. In individual patients, 69% tested t-TG “persistently negative”, 1% “persistently positive” and 30% “intermittently negative or positive”. By applying mathematical modelling to t-TG conversion rates observed in this latter group at beginning and end of the follow-up program, the predicted proportion of t-TG negative population increased from 90% to 95% over 5 years.

Conclusions

Time-course of t-TG serology in the community fluctuates in 1/3 of celiac disease patients suggesting inconstant adherence to gluten-free diet and need of follow-up strategy. Periodical serological and clinical follow-up is a viable and efficacious strategy to promote adherence to gluten-free diet as inferred from time-course of t-TG serology.     

Symptoms and findings in adult-onset celiac disease in a historical Danish patient cohort

Objective: The presentation of celiac disease (CD) has changed over the past decades. We aimed to describe the incidence of CD and its complications at diagnosis in a historical cohort in a well-defined population in Denmark. Methods: We included all patients aged 15+ years, who lived in Aarhus County, Denmark, and who were diagnosed with CD between January 2008 and August 2013. Data regarding gastrointestinal symptoms, anthropometrics, biochemistry, and bone mineral density were retrieved from patient records. Results: A total of 93 patients with a valid CD diagnosis were identified, corresponding to an incidence rate of 6.4 per 100,000 person-years. At diagnosis, diarrhea and weight loss occurred in 54% and 47% patients, respectively. In total, 30% had anemia; 40%, iron deficiency; 20%, folate deficiency; and 17%, vitamin B12 deficiency. Vitamin D deficiency was present in 34%. In 28%, bone mineral density was determined during the first year after diagnosis. Of these, 54% had osteopenia and 12% osteoporosis. After introduction of a gluten-free diet, 28% had normalized transglutaminase antibody levels after 6 months, and 56% did after 12 months. Diabetes mellitus type 1 was present in 7%; dermatitis herpetiformis, in 3%; and thyroid dysfunction, in 5%. Conclusions: Only half of newly diagnosed CD patients presented with classic gastrointestinal symptoms. Anemia and vitamin deficiencies were common. Bone mineral density was determined in less than a third of the patients, and osteoporosis occurred in 12% of these. Serologic markers of CD normalized in approximately half of patients during the first year after the diagnosis.     

Prevalence of celiac disease and celiac autoimmunity in the Toba native Amerindian community of Argentina

BACKGROUND:

Celiac disease (CD) is mostly recognized among subjects with a Caucasian ethnic ancestry. No studies have explored conditions predisposing Amerindians to CD.

OBJECTIVE:

To prospectively assess environmental, genetic and serological conditions associated with CD among members of the Toba native population attending a multidisciplinary sanitary mission.

METHODS:

An expert nutritionist determined daily gluten intake using an established questionnaire. Gene typing for the human leukocyte antigen (HLA) class II alleles was performed on DNA extracted from peripheral blood (HLA DQ2/DQ8 haplotype). Serum antibodies were immunoglobulin (Ig) A tissue transglutaminase (tTG) and the composite deamidated gliadin peptides/tTG Screen test. Positive cases were tested for IgA endomysial antibodies.

RESULTS:

A total of 144 subjects (55% female) were screened. The estimated mean gluten consumption was 43 g/day (range 3 g/day to 185 g/day). Genetic typing showed that 73 of 144 (50.7%) subjects had alleles associated with CD; 69 (94.5%) of these subjects had alleles for HLA DQ8 and four had DQ2 (5.5%). Four and six subjects had antibody concentrations above the cut-off established by the authors’ laboratory (>3 times the upper limit of normal) for IgA tTG and deamidated gliadin peptides/tTG screen, respectively. Four of these had concomitant positivity for both assays and endomysial antibodies were positive in three subjects who also presented a predisposing haplotype.

CONCLUSION:

The present study was the first to detect CD in Amerindians. The native Toba ethnic population has very high daily gluten consumption and a predisposing genetic background. We detected subjects with persistent CD autoimmunity and, at least, three of them fulfilled serological criteria for CD diagnosis.     

Multineuropathy in a patient with HBV infection, polyarteritis nodosa and celiac disease

We report on the first association of celiac disease, polyarteritis nodosa and HBV infection in a patient who developed a neuropathy. On admission his general and neurological conditions were severely compromised. Haematological test revealed HBV infection and high levels of antibodies to tissue transglutaminase, endomysium, gliadin. EMG showed sensory-motor asymmetric axonal neuropathy. A sural nerve biopsy revealed fibre loss, axonal degeneration with asymmetrical distribution and fascicular ischaemia. A duodenal biopsy was consistent with celiac disease. The patient was treated with immunosuppressive and antiviral therapy, and gluten-free diet with good result. Celiac disease can be related to a higher risk of autoimmune disorders and may have contributed to the development of multineuropathy in this patient.     

Systemic lupus erythematosus,celiac disease and antiphospholipid antibody syndrome: a rare association

Association of celiac disease with systemic lupus erythematosus is rare, even though HLA B8 and DR3 are commonly associated with these diseases. We read with great interest a similar case reported by Hrycek and Siekiera in this journal and wish to highlight another case of ours, which had celiac disease, systemic lupus erythematosus and antiphospholipid antibody syndrome, an association which has never been described before.