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

A1M： 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 （EHA） by indirect immunofiuoresence 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 % [gA 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＊0S01/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＊0S01/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-invasive prediction of persistent villous atrophy in celiac disease

BACKGROUND Celiac disease(CD)is an immune-mediated enteropathy that is primarily treated with a gluten-free diet(GFD).Mucosal healing is the main target of the therapy.Currently,duodenal biopsy is the only way to evaluate mucosal healing,and noninvasive markers are challenging.Persistent elevation of anti-tissue transglutaminase antibodies(aTTG)is not an ideal predictor of persistent villous atrophy(VA).Data regarding prediction of atrophy using anti-deamidated gliadin peptide antibodies(aDGP)and abdominal ultrasonography are lacking.AIM To evaluate the ability of aTTG,aDGP,small bowel ultrasonography,and clinical and laboratory parameters in predicting persistent VA determined using histology.METHODS Patients with CD at least 1 year on a GFD and available follow-up duodenal biopsy,levels of aTTG and aDGP,and underwent small bowel ultrasonography were included in this retrospective cohort study.We evaluated the sensitivity,specificity,and positive and negative predictive values of aTTG,aDGP,small bowel ultrasonography,laboratory and clinical parameters to predict persistent VA.A receiver operating characteristic(ROC)curve analysis of antibody levels was used to calculate cut off values with the highest accuracy for atrophy prediction.RESULTS Complete data were available for 82 patients who were followed up over a period of four years(2014-2018).Among patients included in the analysis,women(67,81.7%)were predominant and the mean age at diagnosis was 33.8 years.Followup biopsy revealed persistent VA in 19 patients(23.2%).The sensitivity and specificity of aTTG using the manufacturer’s diagnostic cutoff value to predict atrophy was 50%and 85.7%,respectively,while the sensitivity and specificity of aDGP(using the diagnostic cutoff value)was 77.8%and 75%,respectively.Calculation of an optimal cutoff value using ROC analysis(13.4 U/mL for aTTG IgA and 22.6 U/mL for aDGP IgA)increased the accuracy and reached 72.2%[95%confidence interval(CI):46.5-90.3]sensitivity and 90%(95%CI:79.5-96.2)specificity for aDGP IgA and 66.7%(95%CI:41.0-86.7)sensitivity and 93.7%(95%CI:84.5-98.2)specificity for aTTG IgA.The sensitivity and specificity of small bowel ultrasonography was 64.7%and 73.5%,respectively.A combination of serology with ultrasound imaging to predict persistent atrophy increased the positive predictive value and specificity to 88.9%and 98%for aTTG IgA and to 90.0%and 97.8%for aDGP IgA.Laboratory and clinical parameters had poor predictive values.CONCLUSION The sensitivity,specificity,and negative predictive value of aTTG and aDGP for predicting persistent VA improved by calculating the best cutoff values.The combination of serology and experienced bowel ultrasound examination may achieve better accuracy for the detection of atrophy.

Digesting gluten with oral endopeptidases to improve the management of celiac disease

In our editorial,we want to comment on the article by Stefanolo et al titled“Effect of Aspergillus niger prolyl endopeptidase in patients with celiac disease on a long-term gluten-free diet”.Celiac disease is an immune-mediated disorder triggered by dietary gluten in genetically predisposed individuals.Although avoiding gluten can permit patients to live symptom-free,ongoing voluntary or involuntary exposure to gluten is common and associated with persistent villous atrophy in small bowel mucosa.As villous atrophy predisposes patients to life threatening complications,such as osteoporotic fractures or malignancies,therapeutic adjuncts to gluten-free diet become important to improve patients’quality of life and,if these adjuncts can be shown to improve villous atrophy,avoid complications.Oral administration of enzyme preparations,such as endopeptidases that digest gluten and mitigate its antigenicity to trigger inflam-mation,is one clinical strategy under investigation.The article is about the utility of one endopeptidase isolated from Aspergillus niger.We critique findings of this clinical trial and also summarize endopeptidase-based as well as other strategies and how they can complement gluten-free diet in the management of celiac disease.

Methotrexate induced sprue-like syndrome

A 52 year-old male patient diagnosed of ankylosing spon-dylitis presented with an iron deficiency anemia after a ten-month treatment of methotrexate. He did not respond to treatment with oral iron not a proton pump inhibitor and an upper endoscopy was performed. The histological study of the duodenal biopsies showed villus atrophy. After removing the methotrexate, administrating intra-muscular iron and undertaking a gluten-free diet, the histological and analytical alterations progressively resolved.

Understanding celiac disease monitoring patterns and outcomes after diagnosis:A multinational,retrospective chart review study

BACKGROUND Long-term outcomes and monitoring patterns in real-world practice are largely unknown among patients with celiac disease.AIM To understand patterns of follow-up and management of patients with celiac disease,and to characterize symptoms and villous atrophy after diagnosis.METHODS A retrospective chart review study was performed using medical chart data of patients diagnosed with celiac disease.Three gastroenterology referral centers,with substantial expertise in celiac disease,participated in the United Kingdom,United States,and Norway.Demographic and clinical data were collected from medical charts.Descriptive analyses were conducted on patients with biopsyconfirmed celiac disease,diagnosed between 2008 and 2012,with at least one follow-up visit before December 31,2017.Patient demographic and clinical characteristics,biopsy/serology tests and results,symptoms,and comorbidities were captured at diagnosis and for each clinic visit occurring within the study period(i.e.,before the study end date of December 31,2017).RESULTS A total of 300 patients were included in this study[72%female;mean age at diagnosis:38.9 years,standard deviation(SD)17.2].Patients were followed-up for a mean of 29.9 mo(SD 22.1)and there were,on average,three follow-up visits per patient during the study period.Over two-thirds(68.4%)of patients were recorded as having ongoing gastrointestinal symptoms and 11.0%had ongoing symptoms and enteropathy during follow-up.Approximately 80%of patients were referred to a dietician at least once during the follow-up period.Half(50.0%)of the patients underwent at least one follow-up duodenal biopsy and 36.6%had continued villous atrophy.Patterns of monitoring varied between sites.Biopsies were conducted more frequently in Norway and patients in the United States had a longer follow-up duration.CONCLUSION This real-world study demonstrates variable follow-up of patients with celiac disease despite most patients continuing to have abnormal histology and symptoms after diagnosis.

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.