Celiac disease (CD) is an autoimmune disease with inflammatory characteristics, having a condition of chronic malabsorption, affecting approximately 1% of the population at any age. In recent years, ...a concrete correlation between eating disorders and CD has emerged. Hypothalamus plays a central role in determining eating behaviour, regulating appetite and, consequently, food intake. One hundred and ten sera from celiac patients (40 active and 70 following a gluten-free diet) were tested for the presence of autoantibodies against primate hypothalamic periventricular neurons by immunofluorescence and by a home-made ELISA assay. In addition, ghrelin was measured by ELISA. As control, 45 blood serums from healthy age matched were analysed. Among active CD, all patients resulted positive for anti-hypothalamus autoantibodies and sera showed significantly higher levels of ghrelin. All of the free-gluten CD were negative for anti-hypothalamus autoantibodies and had low levels of ghrelin, as well as healthy controls. Of interest, anti-hypothalamic autoantibodies directly correlate with anti-tTG amounts and with mucosal damage. In addition, competition assays with recombinant tTG showed a drastically reduction of anti-hypothalamic serum reactivity. Finally, ghrelin levels are increased in CD patients and correlated with anti-tTG autoantibodies and anti-hypothalamus autoantibodies. This study demonstrates for the first time the presence of anti-hypothalamus antibodies and their correlation with the severity of the CD. It also allows us to hypothesize the role of tTG as a putative autoantigen expressed by hypothalamic neurons.
In its conventional form, celiac disease (CeD) is characterized by both positive serology and flat villi in the duodenum, and is well known by gastroenterologists and general practitioners. The aim ...of this review was to shed light on 2 neglected and not yet well-defined celiac phenotypes, that is, seronegative and ultrashort CeD. Seronegative CeD can be suspected in the presence of flat villi, positive HLA-DQ2 and/or HLA-DQ8, and the absence of CeD antibodies. After ruling out other seronegative enteropathies, the diagnosis can be confirmed by both clinical and histologic improvements after 1 year of a gluten-free diet. Ultrashort CeD is characterized by the finding of flat villi in the duodenal bulb in the absence of mucosal damage in the distal duodenum and with serologic positivity. Data on the prevalence, clinical manifestations, histologic lesions, genetic features, and outcome of seronegative and ultrashort CeD are inconclusive due to the few studies available and the small number of patients diagnosed. Some additional diagnostic tools have been developed recently, such as assessing intestinal transglutaminase 2 deposits, flow cytometry technique, microRNA detection, or proteomic analysis, and they seem to be useful in the identification of complex cases. Further cooperative studies are highly desirable to improve the knowledge of these 2 still-obscure variants of CeD.
Potential celiac disease is characterized by positive results from serologic tests for tissue transglutaminase antibodies (anti-TG2) but normal duodenal architecture (Marsh stages 0–1). There is ...controversy over the best way to manage these patients. We investigated risk factors associated with the development of villous atrophy in children with potential celiac disease.
We performed a prospective study of 280 children (ages 2–18 years) in Italy with suspected celiac disease, followed for up to 12 years (range, 18–150 months; median 60 months). The subjects had 2 consecutive positive results from tests for anti-TG2, tested positive for the endomysial antibody (anti-EMA), had total serum levels of immunoglobulin A in the normal range, normal duodenal architecture (Marsh stages 0–1) in 5 biopsies, and HLA DQ2- or DQ8-positive haplotypes. The children underwent serologic tests and clinical analyses every 6 months and a small bowel biopsy was taken every 2 years. A total of 210 patients of the original cohort were assessed at the 9-year follow-up evaluation. We performed multivariate analyses of clinical, genetic, and histologic data to identify factors associated with progression to villous atrophy.
During the follow-up period, 42 (15%) of 280 children developed villous atrophy, whereas 89 (32%) children no longer tested positive for anti-TG2 or anti-EMA. The cumulative incidence of progression to villous atrophy was 43% at 12 years. In multivariate analysis, the baseline factors most strongly associated with development of villous atrophy were numbers of γδ intraepithelial lymphocyte cells followed by age and homozygosity for the HLA DQB1*02. In discriminant analysis, these baseline factors identified 80% of the children who developed baseline atrophy.
In a long-term study of 280 children with suspected celiac disease (based on anti-TG2 and anti-EMA) on gluten-containing diets, the cumulative incidence of progression to villous atrophy was 43% over a 12-year period. We identified factors that can be used to identify children at highest risk for villous atrophy. This approach might be used to determine whether children with suspected celiac disease should immediately start a gluten-free diet or be monitored on their regular diet.
Potential celiac disease (CD) is defined by the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies and normal duodenal mucosa. The major clinical problem is the management of ...asymptomatic patients and how to predict the development of villous atrophy. This prospective longitudinal cohort study describes the natural history of potential CD up to 9 years and explores risk factors associated with the development of mucosal damage.
Two hundred and ten potential CD children were eligible for the study; 175/210 asymptomatic children were left on a gluten-containing diet. Antibodies and clinical symptoms were checked every 6 months, and a small bowel biopsy was taken every 2 years to evaluate histological, immunohistochemical, and anti-TG2 deposits. Patients were genotyped for HLA and a set of non-HLA CD-associated genes.
Forty-three percent of patients showed persistently elevated anti-TG2 level, 20% became negative during follow-up, and 37% showed a fluctuant anti-TG2 course with transiently negative values. At 3 years of follow-up, 86% of cases remained potential; 73 and 67% still had normal duodenal architecture at 6 and 9 years, respectively. Male sex, slight mucosal inflammation at time 0, and a peculiar genetic profile delineate a cohort of individuals who were prone to develop mucosal damage during time.
A sizeable proportion of asymptomatic potential celiac patients showed fluctuation or negativization of antibody production, and many of these, with persistently positive anti-TG2, did not develop mucosal damage after 9 years of follow-up. Celiac population is a multivariate aggregate of individuals with different genetic and phenotypic profiles. Caution is required before prescribing a gluten-free diet for life to asymptomatic individuals with potential CD.
A distinctive new species of the Neotropical stingless bee genus Paratrigona Schwarz from northeastern Brazil, previously considered as a variation within P. lineata by Camargo and Moure (1994), is ...described and illustrated. Paratrigona intermedia Oliveira, Madella-Auricchio & Freitas sp. nov. belongs to the lineata group. It is easily distinguished from its congeners by the pattern of body pubescence, especially by the absence of erect setae on the mesoscutum and disc of the mesoscutellum, and the presence of erect setae on the apical border of the mesoscutellum (dorsal and ventral surfaces) and sparse short erect setae on the upper 2/3 of the mesepisternum. The lectotype designation for Melipona lineata Lepeletier, 1836 is provided along with notes on its morphology and the concept of Paratrigona lineata is changed to differentiate it from the new species described here. Paratrigona lineata (Lepeletier, 1836), P. glabella Camargo & Moure, 1994 and P. incerta Camargo & Moure, 1994 are illustrated to facilitate comparisons with the new species. An updated key to the lineata species group, including the new species, is also provided.
http://www.zoobank.org/urn:lsid:zoobank.org:pub:3FA139B8-1FDA-459A-8189-F3785AE25BF1
http://www.zoobank.org/urn:lsid:zoobank.org:act:9D6A8CD7-D8F6-44B2-81CF-E12C01FA0DCD
The reptile diversity of the Middle Gurguéia River Basin in southern Piauí, Brazil, is little known. The rapid expansion of agriculture in the region is converting the Cerrado and Caatinga into large ...farming areas, which threatens biodiversity and hastens its loss. In this study, 68 specimens of reptiles from a university collection were examined, comprising 29 species: ten lizards, one amphisbaenian, 15 snakes, two turtles and one crocodilian. They were collected from five locations in the Middle Gurguéia Basin, a region not previously evaluated for reptiles. The most abundant species is a member of Tropidurus. Comparison with eight other areas in the eastern Parnaíba Basin indicated that the diversity of reptiles in the Middle Gurguéia is similar to that in other Caatinga-Cerrado ecotone areas. The reptile assemblage in the eastern Parnaíba Basin comprises 100 species of reptiles: 39 lizards, five amphisbaenians, 50 snakes, four chelonians and two crocodilians. This study expanded the known distributions of some reptiles and recorded the first occurrence of Helicops leopardinus (Schlegel, 1837) for Piauí. A cluster analysis showed that the reptile composition concords with the habitat where species were found, i.e. Cerrado, Caatinga or ecotone. Studies that associate habitat structure with each species are essential to propose efficient strategies for reptile management and conservation for the entire Parnaíba River Basin, mostly in areas that are not yet protected.
Celiac disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. Some gliadin peptides are resistant to intestinal ...digestion (e.g., A-gliadin P31-43) and induce a stress/innate immune response, but the reason why they are dangerous in the intestines of patients with CD is unknown. In the present study, P31-43 activated IFN-α, a mediator of the innate immune response in CD, in the intestine of subjects with CD and an enterocyte cell line, CaCo-2. P31-43 cooperated with a viral ligand to activate the TLR7 pathway by interfering with endocytic trafficking. Based on these results, the vesicular pathway regulates the innate/inflammatory response to viral ligands and bioactive dietary peptides. Suggesting that together with viral infections, alimentary proteins able to mimic and potentiate the innate immune response to viruses, can trigger an autoimmune disease such as CD.
Scope
Gluten from the diploid wheat Triticum monococcum (TM) has low content of immunostimulatory sequences and a high gastro‐intestinal digestibility. Gluten‐reactive T cells elicited by diploid and ...hexaploid (Triticum aestivum‐TA) wheat in celiac disease (CD) patients upon a brief oral challenge are analyzed.
Methods and results
Seventeen patients with CD (median age 13 years) consumed for 3 days sandwiches made with TM (cultivar Norberto‐ID331, N=11), or TA (cultivar Sagittario, N=11) flours, corresponding to 12 gr of gluten/die. Immunostimulatory properties are assessed in blood by measuring the IFN‐γ‐secreting T cells by EliSpot and the expression of inflammatory cytokines/receptors (IL‐12A, IL‐15, IL‐18RAP, IFN‐γ) by qPCR. TA mobilizes a remarkable number of gliadin‐specific, IFN‐γ‐secreting T cells (p<0.05), while no significant cell mobilization is induced by TM (p=ns). Similar results are obtained in response to five immunogenic peptides from α‐, ω‐, and γ‐gliadins, although with a large individual variability. An increased mRNA expression for IL‐12A and IFN‐γ is detected in the group eating TA compared to those consuming TM (p<0.05).
Conclusions
Although T. monococcum is a cereal not suitable for the diet of celiacs, this diploid wheat elicits a reduced in vivo T‐cell response compared to T. aestivum in celiac patients.
The in vivo immunogenicity of Triticum monococcum (TM) and Triticum aestivum (TA) wheats is assessed in celiacs after 3 days of bread consumption. TM mobilizes a reduced number of IFN‐γ‐secreting‐T cells, and elicits a reduced IL‐12A and IFN‐γ mRNA expression compared to TA (p<0.05). No differences are detected in the expression of IL‐15, IL‐18RAP among the two groups of patients.
There is a need for consensus on the recommendations for follow‐up of children and adolescents with celiac disease.
Objectives:
To gather the current evidence and to offer recommendations for ...follow‐up and management.
Methods:
The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow‐up care. A literature search (January 2010–March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%.
Results:
Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow‐up, its frequency and what should be assessed, how to assess adherence to the gluten‐free diet, when to expect catch‐up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue‐transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten‐challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow‐up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care.
Conclusions:
We offer recommendations to improve follow‐up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.
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