Browsing by Subject "CELIAC-DISEASE"

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  • Haller-Kikkatalo, Kadri; Alnek, Kristi; Metspalu, Andres; Mihailov, Evelin; Metskula, Kaja; Kisand, Kalle; Pisarev, Heti; Salumets, Andres; Uibo, Raivo (2017)
    The presence of autoantibodies usually precedes autoimmune disease, but is sometimes considered an incidental finding with no clinical relevance. The prevalence of immune-mediated diseases was studied in a group of individuals from the Estonian Genome Project (n = 51,862), and 6 clinically significant autoantibodies were detected in a subgroup of 994 (auto) immune-mediated disease-free individuals. The overall prevalence of individuals with immune-mediated diseases in the primary cohort was 30.1%. Similarly, 23.6% of the participants in the disease-free subgroup were seropositive for at least one autoantibody. Several phenotypic parameters were associated with autoantibodies. The results suggest that (i) immune-mediated diseases are diagnosed in nearly one-third of a random European population, (ii) 6 common autoantibodies are detectable in almost one-third of individuals without diagnosed autoimmune diseases, (iii) tissue non-specific autoantibodies, especially at high levels, may reflect preclinical disease in symptom-free individuals, and (iv) the incidental positivity of anti-TPO in men with positive familial anamnesis of maternal autoimmune disease deserves further medical attention. These results encourage physicians to evaluate autoantibodies in addition to treating a variety of patient health complaints to detect autoimmune-mediated disease early.
  • Hervonen, Kaisa; Salmi, Teea T.; Ilus, Tuire; Paasikivi, Kaija; Vornanen, Martine; Laurila, Kaija; Lindfors, Katri; Viiri, Keijo; Saavalainen, Paivi; Collin, Pekka; Kaukinen, Katri; Reunala, Timo (2016)
    Dermatitis herpetiformis (DH) is a blistering skin disease, which is regarded as an extra-intestinal manifestation of coeliac disease. Refractory cases of coeliac disease, that do not respond to a gluten-free diet and which carry an increased risk of lymphoma, are well-known in coeliac disease. To determine whether refractory cases of DH with active rash and persistent small bowel atrophy occur we analysed our series of 403 patients with DH. Seven (1.7%) patients, who had been on a gluten-free diet for a mean of 16 years, but who still required dapsone to treat the symptoms of DH, were identified. Of these, one patient died from mucinous adenocarcinoma before re-examination. At re-examination skin immunoglobulin A (IgA) deposits were found in 5/6 refractory and 3/16 control DH patients with good dietary response. Small bowel mucosa was studied at re-examination from 5 refractory and 8 control DH patients and was normal in all 5 refractory and 7/8 control DH patients. One refractory DH patient died from adenocarcinoma, but no lymphoma developed in any of the patients. This study documents for the first time refractory DH, in which the rash is non-responsive to a gluten-free diet, but the small bowel mucosa heals. This differs from refractory coeliac disease, in which the small bowel mucosa does not heal on a gluten-free diet.
  • Hewetson, Michael; Venner, Monica; Volquardsen, Jan; Sykes, Ben William; Hallowell, Gayle Davina; Vervuert, Ingrid; Fosgate, Geoffrey Theodore; Tulamo, Riitta-Mari (2018)
    Background: Equine gastric ulcer syndrome is an important cause of morbidity in weanling foals. Many foals are asymptomatic, and the development of an inexpensive screening test to ensure an early diagnosis is desirable. The objective of this study was to determine the diagnostic accuracy of blood sucrose for diagnosis of EGUS in weanling foals. Results: 45 foals were studied 7 days before and 14 days after weaning. The diagnostic accuracy of blood sucrose for diagnosis of gastric lesions (GL); glandular lesions (GDL); squamous lesions (SQL) and clinically significant gastric lesions (CSL) at 45 and 90 min after administration of 1 g/kg of sucrose via nasogastric intubation was assessed using ROC curves and calculating the AUC. For each lesion type, sucrose concentration in blood was compared to gastroscopy; and sensitivities (Se) and specificities (Sp) were calculated across a range of sucrose concentrations. Cut- off values were selected manually to optimize Se. Because of concerns over the validity of the gold standard, additional Se, Sp, and lesion prevalence data were subsequently estimated and compared using Bayesian latent class analysis. Using the frequentist approach, the prevalence of GL; GDL; SQL and CSL before weaning was 21; 9; 7 and 8% respectively; and increased to 98; 59; 97 and 82% respectively after weaning. At the selected cut- off, Se ranged from 84 to 95% and Sp ranged from 47 to 71%, depending upon the lesion type and time of sampling. In comparison, estimates of Se and Sp were consistently higher when using a Bayesian approach, with Se ranging from 81 to 97%; and Sp ranging from 77 to 97%, depending upon the lesion type and time of sampling. Conclusions: Blood sucrose is a sensitive test for detecting EGUS in weanling foals. Due to its poor specificity, it is not expected that the sucrose blood test will replace gastroscopy, however it may represent a clinically useful screening test to identify foals that may benefit from gastroscopy. Bayesian latent class analysis represents an alternative method to evaluate the diagnostic accuracy of the blood sucrose test in an attempt to avoid bias associated with the assumption that gastroscopy is a perfect test.
  • Shewry, P. R.; Hassall, K.L.; Grausgruber, H.; Andersson, A.A.M.; Lampi, Anna-Maija; Piironen, Vieno; Rakszegi, Marianne; Ward, Jane L; Lovegrove, L. (2020)
    Wheat is the major staple food in Western Europe and an important source of energy, protein, dietary fibre, minerals, B vitamins and phytochemicals. Plant breeders have been immensely successful in increasing yields to feed the growing global population. However, concerns have been expressed that the focus on increasing yield and processing quality has resulted in reduced contents of components that contribute to human health and increases in adverse reactions. We review the evidence for this, based largely on studies in our own laboratories of sets of wheats bred and grown between the 18(th)century and modern times. With the exception of decreased contents of mineral micronutrients, there is no clear evidence that intensive breeding has resulted in decreases in beneficial components or increases in proteins which trigger adverse responses. In fact, a recent study of historic and modern wheats from the UK showed increases in the contents of dietary fibre components and a decreased content of asparagine in white flour, indicating increased benefits for health.
  • Hänninen, Ulrika A.; Katainen, Riku; Tanskanen, Tomas; Plaketti, Roosa-Maria; Laine, Riku; Hamberg, Jiri; Ristimäki, Ari; Pukkala, Eero; Taipale, Minna; Mecklin, Jukka-Pekka; Forsström, Linda M.; Pitkänen, Esa; Palin, Kimmo; Välimäki, Niko; Mäkinen, Netta; Aaltonen, Lauri A. (2018)
    Small bowel adenocarcinoma (SBA) is an aggressive disease with limited treatment options. Despite previous studies, its molecular genetic background has remained somewhat elusive. To comprehensively characterize the mutational landscape of this tumor type, and to identify possible targets of treatment, we conducted the first large exome sequencing study on a population-based set of SBA samples from all three small bowel segments. Archival tissue from 106 primary tumors with appropriate clinical information were available for exome sequencing from a patient series consisting of a majority of confirmed SBA cases diagnosed in Finland between the years 2003-2011. Paired-end exome sequencing was performed using Illumina HiSeq 4000, and OncodriveFML was used to identify driver genes from the exome data. We also defined frequently affected cancer signalling pathways and performed the first extensive allelic imbalance (Al) analysis in SBA. Exome data analysis revealed significantly mutated genes previously linked to SBA (TP53, KRAS, APC, SMAD4, and BRAF), recently reported potential driver genes (SOX9, ATM, and ARID2), as well as novel candidate driver genes, such as ACVR2A, ACVR1B, BRCA2, and SMARCA4. We also identified clear mutation hotspot patterns in ERBB2 and BRAF. No BRAF V600E mutations were observed. Additionally, we present a comprehensive mutation signature analysis of SBA, highlighting established signatures 1A, 6, and 17, as well as U2 which is a previously unvalidated signature. Finally, comparison of the three small bowel segments revealed differences in tumor characteristics. This comprehensive work unveils the mutational landscape and most frequently affected genes and pathways in SBA, providing potential therapeutic targets, and novel and more thorough insights into the genetic background of this tumor type.
  • Wacklin, Pirjo; Tuimala, Jarno; Nikkila, Janne; Tims, Sebastian; Makivuokko, Harri; Alakulppi, Noora; Laine, Pia; Rajilic-Stojanovic, Mirjana; Paulin, Lars; de Vos, Willem M.; Matto, Jaana (2014)
  • Mansikka, Eriika; Hervonen, Kaisa; Kaukinen, Katri; Ilus, Tuire; Oksanen, Pia; Lindfors, Katri; Laurila, Kaija; Hietikko, Minna; Taavela, Juha; Jernman, Juha; Saavalainen, Päivi; Reunala, Timo; Salmi, Teea (2019)
    Dermatitis herpetiformis (DH) is an extraintestinal manifestation of celiac disease causing an itchy, blistering rash. Granular IgA deposits in the skin are pathognomonic for DH, and the treatment of choice is a lifelong gluten-free diet (GFD). Preliminary evidence suggests that there are patients with DH who redevelop gluten tolerance after adherence to a GFD treatment. To evaluate this, we performed a 12-month gluten challenge with skin and small-bowel mucosal biopsy samples in 19 patients with DH who had adhered to a GFD for a mean of 23 years. Prechallenge biopsy was negative for skin IgA and transglutaminase 3 deposits in 16 patients (84%) and indicated normal villous height-to-crypt depth ratios in the small bowel mucosa in all 19 patients. The gluten challenge caused a relapse of the rash in 15 patients (79%) in a mean of 5.6 months; of these 15 patients, 13 had skin IgA and transglutaminase 3 deposits, and 12 had small-bowel villous atrophy. In addition, three patients without rash or immune deposits in the skin developed villous atrophy, whereas one patient persisted without any signs of relapse. In conclusion, 95% of the patients with DH were unable to tolerate gluten even after long-term adherence to a GFD. Therefore, lifelong GFD treatment remains justified in all patients with DH.
  • Parkkola, Anna; Laine, Antti-Pekka; Karhunen, Markku; Härkönen, Taina; Ryhänen, Samppa J.; Ilonen, Jorma; Knip, Mikael; Finnish Pediat Diabet Register (2017)
    Genetic predisposition could be assumed to be causing clustering of autoimmunity in individuals and families. We tested whether HLA and non-HLA loci associate with such clustering of autoimmunity. We included 1,745 children with type 1 diabetes from the Finnish Pediatric Diabetes Register. Data on personal or family history of autoimmune diseases were collected with a structured questionnaire and, for a subset, with a detailed search for celiac disease and autoimmune thyroid disease. Children with multiple autoimmune diseases or with multiple affected first-or second-degree relatives were identified. We analysed type 1 diabetes related HLA class II haplotypes and genotyped 41 single nucleotide polymorphisms (SNPs) outside the HLA region. The HLA-DR4-DQ8 haplotype was associated with having type 1 diabetes only whereas the HLA-DR3-DQ2 haplotype was more common in children with multiple autoimmune diseases. Children with multiple autoimmune diseases showed nominal association with RGS1 (rs2816316), and children coming from an autoimmune family with rs11711054 (CCR3-CCR5). In multivariate analyses, the overall effect of non-HLA SNPs on both phenotypes was evident, associations with RGS1 and CCR3-CCR5 region were confirmed and additional associations were implicated: NRP1, FUT2, and CD69 for children with multiple autoimmune diseases. In conclusion, HLA-DR3-DQ2 haplotype and some non-HLA SNPs contribute to the clustering of autoimmune diseases in children with type 1 diabetes and in their families.
  • Hiippala, Kaisa; Kainulainen, Veera; Kalliomaki, Marko; Arkkila, Perttu; Satokari, Reetta (2016)
    Sutterella species have been frequently associated with human diseases, such as autism, Down syndrome, and inflammatory bowel disease (IBD), but the impact of these bacteria on health still remains unclear. Especially the interactions of Sutterella spp. with the host are largely unknown, despite of the species being highly prevalent. In this study, we addressed the interaction of three known species of Sutterella with the intestinal epithelium and examined their adhesion properties, the effect on intestinal barrier function and the pro-inflammatory capacity in vitro. We also studied the relative abundance and prevalence of the genus Sutterella and Sutterella wadsworthensis in intestinal biopsies of healthy individuals and patients with celiac disease (CeD) or IBD. Our results show that Sutterella spp. are abundant in the duodenum of healthy adults with a decreasing gradient toward the colon. No difference was detected in the prevalence of Sutterella between the pediatric IBD or CeD patients and the healthy controls. Sutterella parvirubra adhered better than the two other Sutterella spp. to differentiated Caco-2 cells and was capable of decreasing the adherence of S. wadsworthensis, which preferably bound to mucus and human extracellular matrix proteins. Furthermore, only S. wadsworthensis induced an interleukin-8 production in enterocytes, which could be due to different lipopolysaccharide structures between the species. However, its pro-inflammatory activity was modest as compared to non-pathogenic Escherichia coli. Sutterella spp. had no effect on the enterocyte monolayer integrity in vitro. Our findings indicate that the members of genus Sutterella are widely prevalent commensals with mild pro-inflammatory capacity in the human gastrointestinal tract and do not contribute significantly to the disrupted epithelial homeostasis associated with microbiota dysbiosis and increase of Proteobacteria. The ability of Sutterella spp. to adhere to intestinal epithelial cells indicate that they may have an immunomodulatory role.
  • Stassen, Q. E. M.; Koskinen, L. L. E.; van Steenbeek, F. G.; Seppala, E. H.; Jokinen, T. S.; Prins, P. G. M.; Bok, H. G. J.; Zandvliet, M. M. J. M.; Vos-Loohuis, M.; Leegwater, P. A. J.; Lohi, H. (2017)
    Background: In the last decade, a disorder characterized by episodes of involuntary movements and dystonia has been recognized in Border Terriers. Objectives: To define clinical features of paroxysmal dyskinesia (PD) in a large number of Border Terriers and to study the genetics of the disease. Animals: 110 affected and 128 unaffected client-owned Border Terriers. Methods: A questionnaire regarding clinical characteristics of PD was designed at Utrecht University and the University of Helsinki. Thirty-five affected Border Terriers underwent physical examination and blood testing (hematology and clinical biochemistry). Diagnostic imaging of the brain was performed in 17 affected dogs and electroencephalograms (EEG) between episodes were obtained in 10 affected dogs. A genomewide association study (GWAS) was performed with DNA of 110 affected and 128 unaffected dogs. Results: One hundred forty-seven questionnaires were included in the study. The most characteristic signs during episodes were dystonia, muscle fasciculations, and falling over. The majority of owners believed that their dogs remained conscious during the episodes. A beneficial effect of anti-epileptic therapy was observed in 29 of 43 dogs. Fifteen owners changed their dogs' diet to a hypoallergenic, gluten-free diet, and all reported reasonable to good improvement of signs. Clinical examinations and diagnostic test results were unremarkable. The GWAS did not identify significantly associated chromosome regions. Conclusions and Clinical Importance: The survey results and EEG studies provided further evidence that the observed syndrome is a PD rather than epilepsy. Failure to achieve conclusive results by GWAS indicates that inheritance of PD in Border Terriers probably is complex.
  • Huang, Xin; Kanerva, Paivi; Salovaara, Hannu; Stoddard, Frederick L.; Sontag-Strohm, Tuula (2017)
    The concentration of residual barley prolamin (hordein) in gluten-free products is overestimated by the R5 ELISA method when calibrated against the wheat gliadin standard. The reason for this may be that the composition of the gliadin standard is different from the composition of hordeins. This study showed that the recognition of whole hordein by R5 antibody mainly came from C-hordein, which is more reactive than the other hordeins. The proportion of C-hordein in total hordein ranged from 16 to 33% of common Finnish barley cultivars used in this study and was always higher than that of omega-gliadin, the homologous protein class in the gliadin standard, which may account for the overestimation. Thus, a hordein standard is needed for barley prolamin quantification instead of the gliadin standard. When gluten-free oat flour was spiked with barley flour, the prolamin concentration was overestimated 1.8-2.5 times with the gliadin standard, whereas estimates in the correct range were obtained when the standard was 40% C-hordein mixed with an inert protein. A preparative-scale method was developed to isolate and purify C-hordein, and C-hordein is proposed as a reference material to calibrate barley prolamin quantification in R5-based assays.
  • Graça, Carla; Lima, Ana; Raymundo, Anabela; Sousa, Isabel (2021)
    Cereal products are staple foods highly appreciated and consumed worldwide. Nonetheless, due to the presence of gluten proteins, and other co‐existing compounds such as amylase‐trypsin inhibitors and fermentable short‐chain carbohydrates in those products, their preference by consumers has substantially decreased. Gluten affects the small gut of people with celiac disease, triggering a gut inflammation condition via auto‐immune response, causing a cascade of health disorders. Amylase‐trypsin inhibitors and fermentable short‐chain carbohydrate compounds that co‐exists with gluten in the cereal‐based foods matrix have been associated with several gastrointestinal symptoms in non‐celiac gluten sensitivity. Since the symptoms are somewhat overlapped, the relation between celiac disease and irritable bowel syndrome has recently received marked interest by researchers. Sourdough fermentation is one of the oldest ways of bread leavening, by lactic acid bacteria and yeasts population, converting cereal flour into attractive, tastier, and more digestible end‐products. Lactic acid bacteria acidification in situ is a key factor to activate several cereal enzymes as well as the synthesis of microbial active metabolites, to positively influence the nutritional/functional and health‐promoting benefits of the derived products. This review aims to explore and highlight the potential of sourdough fermentation in the Food Science and Technology field.
  • Lehto, Markku; Groop, Per-Henrik (2018)
    Diabetic kidney disease (DKD) is a devastating condition associated with increased morbidity and premature mortality. The etiology of DKD is still largely unknown. However, the risk of DKD development and progression is most likely modulated by a combination of genetic and environmental factors. Patients with autoimmune diseases, like type 1 diabetes, inflammatory bowel disease, and celiac disease, share some genetic background. Furthermore, gastrointestinal disorders are associated with an increased risk of kidney disease, although the true mechanisms have still to be elucidated. Therefore, the principal aim of this review is to evaluate the impact of disturbances in the gastrointestinal tract on the development of renal disorders.
  • Geisslitz, Sabrina; Shewry, Peter; Brouns, Fred; America, Antoine H. P.; Caio, Giacomo Pietro Ismaele; Daly, Matthew; D'Amico, Stefano; De Giorgio, Roberto; Gilissen, Luud; Grausgruber, Heinrich; Huang, Xin; Jonkers, Daisy; Keszthelyi, Daniel; Larre, Colette; Masci, Stefania; Mills, Clare; Moller, Marie Sofie; Sorrells, Mark E.; Svensson, Birte; Zevallos, Victor F.; Weegels, Peter Louis (2021)
    Amylase/trypsin-inhibitors (ATIs) comprise about 2-4% of the total wheat grain proteins and may contribute to natural defense against pests and pathogens. However, they are currently among the most widely studied wheat components because of their proposed role in adverse reactions to wheat consumption in humans. ATIs have long been known to contribute to IgE-mediated allergy (notably Bakers' asthma), but interest has increased since 2012 when they were shown to be able to trigger the innate immune system, with attention focused on their role in coeliac disease which affects about 1% of the population and, more recently, in non-coeliac wheat sensitivity which may affect up to 10% of the population. This has led to studies of their structure, inhibitory properties, genetics, control of expression, behavior during processing, effects on human adverse reactions to wheat and, most recently, strategies to modify their expression in the plant using gene editing. We therefore present an integrated account of this range of research, identifying inconsistencies, and gaps in our knowledge and identifying future research needs. Note This paper is the outcome of an invited international ATI expert meeting held in Amsterdam, February 3-5 2020
  • Virta, Johannes; Hannula, Markus; Tamminen, Ilmari; Lindfors, Katri; Kaukinen, Katri; Popp, Alina; Taavela, Juha; Saavalainen, Päivi; Hiltunen, Pauliina; Hyttinen, Jari; Kurppa, Kalle (2020)
    The often poorly orientated small-bowel mucosal biopsies taken for the diagnostics of celiac disease and other intestinal disorders are prone to misinterpretation. Furthermore, conventional histopathology has suboptimal sensitivity for early histopathological changes observed in short-term challenge studies. X-ray microtomography (micro-CT) is a promising new method for accurate imaging of human-derived biological samples. Here, we report that micro-CT could be utilized to create virtual reconstructions of endoscopically obtained intestinal biopsies. The formed digital 3D images enabled selection of always optimal cutting angles for accurate measurement of the mucosal damage and revealed diagnostic lesions in cases interpreted as normal with conventional histomorphometry. We also demonstrate that computer-assisted point cloud analysis can be used to calculate biologically meaningful surface areas of the biopsies in different stages of mucosal damage with excellent replicability and correlation with other disease parameters. We expect the improved diagnostic accuracy and capability to measure the surface areas to provide a powerful tool for the diagnostics of intestinal diseases and for future clinical and pharmaceutical trials.