Vitamin and Mineral Deficiencies Are Highly Prevalent in Newly Diagnosed Celiac Disease Patients

Malabsorption, weight loss and vitamin/mineral-deficiencies characterize classical celiac disease (CD). This study aimed to assess the nutritional and vitamin/mineral status of current “early diagnosed” untreated adult CD-patients in the Netherlands. Newly diagnosed adult CD-patients were included (n = 80, 42.8 ± 15.1 years) and a comparable sample of 24 healthy Dutch subjects was added to compare vitamin concentrations. Nutritional status and serum concentrations of folic acid, vitamin A, B6, B12, and (25-hydroxy) D, zinc, haemoglobin (Hb) and ferritin were determined (before prescribing gluten free diet). Almost all CD-patients (87%) had at least one value below the lower limit of reference. Specifically, for vitamin A, 7.5% of patients showed deficient levels, for vitamin B6 14.5%, folic acid 20%, and vitamin B12 19%. Likewise, zinc deficiency was observed in 67% of the CD-patients, 46% had decreased iron storage, and 32% had anaemia. Overall, 17% were malnourished (>10% undesired weight loss), 22% of the women were underweight (Body Mass Index (BMI) < 18.5), and 29% of the patients were overweight (BMI > 25). Vitamin deficiencies were barely seen in healthy controls, with the exception of vitamin B12. Vitamin/mineral deficiencies were counter-intuitively not associated with a (higher) grade of histological intestinal damage or (impaired) nutritional status. In conclusion, vitamin/mineral deficiencies are still common in newly “early diagnosed” CD-patients, even though the prevalence of obesity at initial diagnosis is rising. Extensive nutritional assessments seem warranted to guide nutritional advices and follow-up in CD treatment

Cross-validation of survival associated biomarkers in gastric cancer using transcriptomic data of 1,065 patients

INTRODUCTION: Multiple gene expression based prognostic biomarkers have been repeatedly identified in gastric carcinoma. However, without confirmation in an independent validation study, their clinical utility is limited. Our goal was to establish a robust database enabling the swift validation of previous and future gastric cancer survival biomarker candidates. RESULTS: The entire database incorporates 1,065 gastric carcinoma samples, gene expression data. Out of 29 established markers, higher expression of BECN1 (HR = 0.68, p = 1.5E-05), CASP3 (HR = 0.5, p = 6E-14), COX2 (HR = 0.72, p = 0.0013), CTGF (HR = 0.72, p = 0.00051), CTNNB1 (HR = 0.47, p = 4.3E-15), MET (HR = 0.63, p = 1.3E-05), and SIRT1 (HR = 0.64, p = 2.2E-07) correlated to longer OS. Higher expression of BIRC5 (HR = 1.45, p = 1E-04), CNTN1 (HR = 1.44, p = 3.5E- 05), EGFR (HR = 1.86, p = 8.5E-11), ERCC1 (HR = 1.36, p = 0.0012), HER2 (HR = 1.41, p = 0.00011), MMP2 (HR = 1.78, p = 2.6E-09), PFKB4 (HR = 1.56, p = 3.2E-07), SPHK1 (HR = 1.61, p = 3.1E-06), SP1 (HR = 1.45, p = 1.6E-05), TIMP1 (HR = 1.92, p = 2.2E- 10) and VEGF (HR = 1.53, p = 5.7E-06) were predictive for poor OS. MATERIALS AND METHODS: We integrated samples of three major cancer research centers (Berlin, Bethesda and Melbourne datasets) and publicly available datasets with available follow-up data to form a single integrated database. Subsequently, we performed a literature search for prognostic markers in gastric carcinomas (PubMed, 2012-2015) and re-validated their findings predicting first progression (FP) and overall survival (OS) using uni- and multivariate Cox proportional hazards regression analysis. CONCLUSIONS: The major advantage of our analysis is that we evaluated all genes in the same set of patients thereby making direct comparison of the markers feasible. The best performing genes include BIRC5, CASP3, CTNNB1, TIMP-1, MMP-2, SIRT, and VEGF

Review article : coeliac disease in later life must not be missed

Background: The presenting symptoms of coeliac disease are often subtle and the diagnosis is frequently delayed or overlooked. Therefore, especially elderly patients may be denied the benefits conferred by gluten free diet which can be dramatically life-changing. Aim: To review the occurrence, clinical features, diagnosis and management in coeliac patients detected later in life. Methods: To review manuscripts concerned with coeliac disease in the elderly and to derive subgroups of elderly people from publications on the disorder. Results: Approximately a quarter of all diagnoses are now made at the age of 60 years or more and a fifth at 65 years or over. About 4% are diagnosed at 80 years or above. Around 60% remain undetected, since their symptoms are often subtle: tiredness, indigestion, reduced appetite. Good compliance with gluten free diet, resolution of symptoms and improvement in laboratory indices can be achieved in over 90% of patients. Conclusions: Coeliac disease not uncommonly presents for the first time in older patients and is an important diagnosis to make.Peer reviewe

Delayed diagnosis of coeliac disease increases cancer risk

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Linkage analysis of HLA and candidate genes for celiac disease in a North American family-based study

BACKGROUND: Celiac disease has a strong genetic association with HLA. However, this association only explains approximately half of the sibling risk for celiac disease. Therefore, other genes must be involved in susceptibility to celiac disease. We tested for linkage to genes or loci that could play a role in pathogenesis of celiac disease. METHODS: DNA samples, from members of 62 families with a minimum of two cases of celiac disease, were genotyped at HLA and at 13 candidate gene regions, including CD4, CTLA4, four T-cell receptor regions, and 7 insulin-dependent diabetes regions. Two-point and multipoint heterogeneity LOD (HLOD) scores were examined. RESULTS: The highest two-point and multipoint HLOD scores were obtained in the HLA region, with a two-point HLOD of 3.1 and a multipoint HLOD of 5.0. For the candidate genes, we found no evidence for linkage. CONCLUSIONS: Our significant evidence of linkage to HLA replicates the known linkage and association of HLA with CD. In our families, likely candidate genes did not explain the susceptibility to celiac disease

Autoantibodies against MHC class I polypeptide-related sequence A are associated with increased risk of concomitant autoimmune diseases in celiac patients

Background: Overexpression of autologous proteins can lead to the formation of autoantibodies and autoimmune diseases. MHC class I polypeptide-related sequence A (MICA) is highly expressed in the enterocytes of patients with celiac disease, which arises in response to gluten. The aim of this study was to investigate anti-MICA antibody formation in patients with celiac disease and its association with other autoimmune processes. Methods: We tested serum samples from 383 patients with celiac disease, obtained before they took up a gluten-free diet, 428 patients with diverse autoimmune diseases, and 200 controls for anti-MICA antibodies. All samples were also tested for anti-endomysium and anti-transglutaminase antibodies. Results: Antibodies against MICA were detected in samples from 41.7% of patients with celiac disease but in only 3.5% of those from controls (P <0.0001) and 8.2% from patients with autoimmune disease (P <0.0001). These antibodies disappeared after the instauration of a gluten-free diet. Anti-MICA antibodies were significantly prevalent in younger patients (P <0.01). Fifty-eight patients with celiac disease (15.1%) presented a concomitant autoimmune disease. Anti-MICA-positive patients had a higher risk of autoimmune disease than MICA antibody-negative patients (P <0.0001; odds ratio = 6.11). The risk was even higher when we also controlled for age (odds ratio = 11.69). Finally, we found that the associated risk of developing additional autoimmune diseases was 16 and 10 times as high in pediatric patients and adults with anti-MICA, respectively, as in those without. Conclusions: The development of anti-MICA antibodies could be related to a gluten-containing diet, and seems to be involved in the development of autoimmune diseases in patients with celiac disease, especially younger ones