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https://www.readbyqxmd.com/read/27861808/peptidomic-analysis-of-type-1-diabetes-associated-hla-dq-molecules-and-the-impact-of-hla-dm-on-peptide-repertoire-editing
#1
Zemin Zhou, Eduardo Reyes-Vargas, Hernando Escobar, Kuan Y Chang, Adam P Barker, Alan L Rockwood, Julio C Delgado, Xiao He, Peter E Jensen
HLA-DM and class II associated invariant chain (Ii) are key cofactors in the MHC class II (MHCII) antigen processing pathway. We used tandem mass spectrometry sequencing to directly interrogate the global impact of DM and Ii on the repertoire of MHCII-bound peptides in human embryonic kidney 293T cells expressing HLA-DQ molecules in the absence or presence of these cofactors. Ii and DM have a major impact on the repertoire of peptides presented by DQ1 and DQ6, with the caveat that this technology is not quantitative...
November 15, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27822952/sprue-like-enteropathy-associated-with-olmesartan-in-a-patient-with-villous-atrophy-hla-dq2-genotype-and-antinuclear-antibodies
#2
Isidro Machado, María Reolid, Fernando Martínez de Juan, Carmen Martínez Lapiedra, Fernanda Maia de Alcántara
We describe a new case of enteropathy with villous atrophy in a patient suffering from arterial hypertension treated with olmesartan. The molecular and serological studies showed anti-nuclear antibodies (ANA) and haplotype HLA-DQ2 positive, as well as negative results for anti-transglutaminase, anti-endomysium and anti-enterocytes antibodies. A duodenal villous atrophy was suspected by upper gastrointestinal endoscopy, which was confirmed by histopathology. The morphological picture was suggestive of sprue-like enteropathy with severe lymphoid infiltration and predominant T lymphoid cells...
November 2016: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/27809896/the-increased-ability-to-present-citrullinated-peptides-is-not-unique-to-hla-se-molecules-arginine-to-citrulline-conversion-also-enhances-peptide-affinity-for-hla-dq-molecules
#3
Arieke S B Kampstra, Jurgen van Heemst, Antonis K Moustakas, George K Papadopoulos, Tom W J Huizinga, René E M Toes
BACKGROUND: Presentation of citrullinated neo-epitopes by HLA-DRB1 molecules that carry the shared epitope (SE) sequence was proposed to explain the association between HLA and seropositive RA. Although it is shown that several HLA-DRB1-SE molecules display enhanced binding affinities for citrullinated ligands, the ability of other HLA molecules to present citrullinated epitopes has not been investigated in a systematic manner. To better understand the HLA-RA connection, we aimed to investigate if the enhanced capacity to present arginine-to-citrulline-converted peptides is unique for HLA-SE alleles...
November 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27798614/analysis-of-self-antigen-specificity-of-islet-infiltrating-t-cells-from-human-donors-with-type-1-diabetes
#4
Jenny Aurielle B Babon, Megan E DeNicola, David M Blodgett, Inne Crèvecoeur, Thomas S Buttrick, René Maehr, Rita Bottino, Ali Naji, John Kaddis, Wassim Elyaman, Eddie A James, Rachana Haliyur, Marcela Brissova, Lut Overbergh, Chantal Mathieu, Thomas Delong, Kathryn Haskins, Alberto Pugliese, Martha Campbell-Thompson, Clayton Mathews, Mark A Atkinson, Alvin C Powers, David M Harlan, Sally C Kent
A major therapeutic goal for type 1 diabetes (T1D) is to induce autoantigen-specific tolerance of T cells. This could suppress autoimmunity in those at risk for the development of T1D, as well as in those with established disease who receive islet replacement or regeneration therapy. Because functional studies of human autoreactive T cell responses have been limited largely to peripheral blood-derived T cells, it is unclear how representative the peripheral T cell repertoire is of T cells infiltrating the islets...
October 31, 2016: Nature Medicine
https://www.readbyqxmd.com/read/27746399/celiac-diseasewith-negative-hla-dq2-5-8-in-spain-asystematic-review-and-meta-analysis
#5
Fernando Fernández-Bañares, Beatriz Arau, Romina Dieli-Crimi, Mercè Rosinach, Concepción Nuñez, Maria Esteve
No abstract text is available yet for this article.
October 13, 2016: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/27721507/the-relationships-between-hla-class-ii-alleles-and-antigens-with-gestational-diabetes-mellitus-a-meta-analysis
#6
Cong-Cong Guo, Yi-Mei Jin, Kenneth Ka Ho Lee, Guang Yang, Chun-Xia Jing, Xuesong Yang
Gestational diabetes mellitus (GDM) is defined as glucose intolerance with onset or first recognition during pregnancy. It is associated with an increased risk of pregnancy complications. Susceptibility to GDM is partly determined by genetics and linked with type 1 diabetes-associated high risk HLA class II genes. However, the evidence for this relationship is still highly controversial. In this study, we assessed the relationship between HLA class II variants and GDM. We performed meta-analysis on all of literatures available in PubMed, Embase, Web of Science and China National Knowledge Infrastructure databases...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27706458/prevalence-of-genetic-susceptibility-for-celiac-disease-in-blood-donors-in-s%C3%A3-o-paulo-brazil
#7
Janaína Guilhem Muniz, Vera Lucia Sdepanian, Ulysses Fagundes
Background: Celiac disease is a permanent intolerance induced by gluten, which is expressed by T-cell mediated enteropathy, and has a high prevalence in the general population. There is evidence of a strong genetic predisposition to celiac disease. Objective: To determine the prevalence of genetic markers HLA-DQ2 and HLA-DQ8 in blood donors from São Paulo and measure human recombinant tissue transglutaminase antibody IgA class in HLA-DQ2 and HLA-DQ8 positive donors...
October 2016: Arquivos de Gastroenterologia
https://www.readbyqxmd.com/read/27695975/long-term-response-to-gluten-free-diet-as-evidence-for-non-celiac-wheat-sensitivity-in-one-third-of-patients-with-diarrhea-dominant-and-mixed-type-irritable-bowel-syndrome
#8
Christian Barmeyer, Michael Schumann, Tim Meyer, Christina Zielinski, Torsten Zuberbier, Britta Siegmund, Jörg-Dieter Schulzke, Severin Daum, Reiner Ullrich
PURPOSE: Irritable bowel syndrome (IBS) is common but therapies are unsatisfactory. Food is often suspected as cause by patients, but diagnostic procedures, apart from allergy testing, are limited. Based on the hypothesis of non-celiac wheat sensitivity (WS) in a subgroup of IBS patients, we tested the long-term response to a gluten-free diet (GFD) and investigated HLA-DQ2 or -DQ8 expression as a diagnostic marker for WS in diarrhea-dominant (IBS-D) and mixed-type IBS (IBS-M). METHODS: The response to a GFD served as reference test for WS and HLA-DQ2/8 expression was determined as index test...
September 30, 2016: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/27670799/a-population-wide-applicable-hla-dq2-and-dq8-genotyping-using-dna-from-dried-blood-spots-and-duplex-allele-specific-qpcr-amplification
#9
Sandra Aguayo-Patrón, Lizbeth Beltrán-Sauceda, Ana María Calderón de la Barca
Genotyping of HLA-DQ2 and DQ8 haplotypes is important for diagnosis or for screening of early risk detection of celiac disease or type 1 diabetes. Usually, venous blood DNA extraction and expensive and time consuming amplification are used, that hinder population-wide studies. We assayed a friendly HLA-DQ2 and DQ8 genotyping procedure using a combination of DNA from dried blood spot (DBS) and duplex allele-specific qPCR amplification using SYBR Green. DNA was extracted using home-made buffers and compared to an extraction commercial kit...
November 2016: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/27659035/coeliac-disease-immunogenicity-studies-of-barley-hordein-and-rye-secalin-derived-peptides
#10
Widya A Wahab, Tanja Šuligoj, Julia Ellis, Beatriz Côrtez-Real, Paul J Ciclitira
Coeliac disease (CD) is an inflammatory disorder of the small intestine. It includes aberrant adaptive immunity with presentation of CD toxic gluten peptides by HLA-DQ2 or DQ8 molecules to gluten-sensitive T cells. A ω-gliadin/C-hordein peptide (QPFPQPEQPFPW) and a rye-derived secalin peptide (QPFPQPQQPIPQ) were proposed to be toxic in CD, as they yielded positive responses when assessed with peripheral blood T-cell clones derived from individuals with CD. We sought to assess the immunogenicity of the candidate peptides using gluten-sensitive T-cell lines obtained from CD small intestinal biopsies...
August 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27658824/hemophagocytic-lymphohistiocytosis-responding-to-withdrawal-of-gluten-a-case-report
#11
Nicholas J Fordham, Richa Ajitsaria, Leena Karnik, Subarna Chakravorty
BACKGROUND: This is the first documented case of a patient with hemophagocytic lymphohistiocytosis in association with coeliac disease. There was complete clinical and biochemical remission of hemophagocytic lymphohistiocytosis following the introduction of a gluten-free diet. CASE PRESENTATION: A 7-year-old white girl presented with fevers and maculopapular rash with a recent history of tonsillitis. Blood tests revealed thrombocytopenia (64×10(9)/L), anemia (80 g/L), hypofibrinogenemia (1 g/L), and hyperferritinemia (71,378 μg/L)...
2016: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/27605538/the-clinical-and-phenotypical-assessment-of-seronegative-villous-atrophy-a-prospective-uk-centre-experience-evaluating-200-adult-cases-over-a-15-year-period-2000-2015
#12
Imran Aziz, Mohammad F Peerally, Jodie-Hannah Barnes, Vigneswaran Kandasamy, Jack C Whiteley, David Partridge, Patricia Vergani, Simon S Cross, Peter H Green, David S Sanders
BACKGROUND: Seronegative villous atrophy (SNVA) is commonly attributed to coeliac disease (CD). However, there are other causes of SNVA. More recently angiotensin-2-receptor-blockers (A2RBs) have been reported as an association but data on SNVA have been limited to centres evaluating complex case referrals and not SNVA in general. OBJECTIVES: To provide clinical outcomes and associations in a large prospective study overseeing all newcomers with SNVA. DESIGN: Over a 15-year period (2000-2015) we evaluated 200 adult patients with SNVA at a UK centre...
September 7, 2016: Gut
https://www.readbyqxmd.com/read/27543737/frequency-of-hla-dqb1-0201-02-and-dqb1-0302-alleles-and-tissue-transglutaminase-antibody-seropositivity-in-children-with-type-1-diabetes-mellitus
#13
Thanita Thammarakcharoen, Nattiya Hirankarn, Taninee Sahakitrungruang, Thanunrat Thongmee, Pavinee Kuptawintu, Sriprapai Kanoonthong, Voranush Chongsrisawat
BACKGROUND: Patients with type 1 diabetes mellitus (T1DM) have an increased risk for celiac disease (CD). Both diseases have a common genetic susceptibility locus in the human leukocyte antigen (HLA) class II alleles. Testing for tissue transglutaminase antibodies (anti-tTG) is highly accurate for CD diagnosis. OBJECTIVE: To determine the frequency of HLA-DQB1*0201/02and DQB1*0302 alleles and anti-tTG seropositivity in children with T1DM. METHODS: Forty-six children with T1DM (male:female=24:22; mean age 12±3...
August 16, 2016: Asian Pacific Journal of Allergy and Immunology
https://www.readbyqxmd.com/read/27513237/celiac-disease-in-children-with-chronic-constipation
#14
Murat Çakir, Seçil Cezaroğlu, Ümit Çobanoğlu
BACKGROUND/AIM: Chronic constipation (CC) and celiac disease (CD) are the most common conditions encountered in pediatric gastroenterology. The association of these two disorders has not been evaluated properly. We analyzed the prevalence and outcome of CD in children with CC. MATERIALS AND METHODS: The study included children with CC (n = 313) and healthy children (n = 990). Serum IgA and IgA antitissue transglutaminase antibodies (IgA-tTG) were studied in all subjects...
2016: Turkish Journal of Medical Sciences
https://www.readbyqxmd.com/read/27486523/the-first-cases-of-collagenous-sprue-successfully-treated-with-thioguanine
#15
Tom van Gils, Tine van de Donk, Gerd Bouma, Foke van Delft, E Andra Neefjes-Borst, Chris J J Mulder
OBJECTIVE: Collagenous sprue (CS) is a rare form of small bowel enteropathy characterised by a thickened basement membrane and is, in most of the literature, reported as part of coeliac disease. Multiple treatment strategies are suggested in CS, but there is no standardised therapy. The aim of this series is to describe 4 cases of CS and to propose thioguanine (6-TG) treatment. DESIGN: We reviewed 4 cases of CS. Data were obtained from our prospective database of patients referred to our coeliac centre...
2016: BMJ Open Gastroenterology
https://www.readbyqxmd.com/read/27449795/shared-and-unique-common-genetic-determinants-between-pediatric-and-adult-celiac-disease
#16
Sabyasachi Senapati, Ajit Sood, Vandana Midha, Neena Sood, Suresh Sharma, Lalit Kumar, B K Thelma
BACKGROUND: Based on age of presentation, celiac disease (CD) is categorised as pediatric CD and adult CD. It however remains unclear if these are genetically and/or phenotypically distinct disorders or just different spectrum of the same disease. We therefore explored the common genetic components underlying pediatric and adult CD in a well characterized north Indian cohort. METHODS: A retrospective analysis of children (n = 531) and adult (n = 871) patients with CD between January 2001 and December 2010 was done...
2016: BMC Medical Genomics
https://www.readbyqxmd.com/read/27411439/environmental-factors-in-the-etiology-of-type-1-diabetes-celiac-disease-and-narcolepsy
#17
REVIEW
Åke Lernmark
The etiology of human leukocyte antigen (HLA)-associated organ-specific autoimmune diseases is incomplete. In type 1 diabetes and celiac disease, the strongest associations are with the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, whereas the DQB1*06:02 allele has a strong negative association. In contrast, narcolepsy, especially as recently triggered by the Pandemrix(®) H1N1 vaccine (GlaxoKlineSmith (GSK), Brentford, Middlesex, UK), did not seem to develop without at least one copy of the latter allele. The overall hypothesis is that the role of these different HLA haplotypes, especially in Finland and Sweden, is related to the immune response to infectious agents that are common in these two populations...
July 2016: Pediatric Diabetes
https://www.readbyqxmd.com/read/27411431/genetic-susceptibility-to-type-1-diabetes-in-childhood%C3%A2-%C3%A2-estimation-of-hla-class-ii-associated-disease-risk-and-class-ii-effect-in-various-phases-of-islet-autoimmunity
#18
J Ilonen, M Kiviniemi, J Lempainen, O Simell, J Toppari, R Veijola, M Knip
OBJECTIVE: The HLA-DR/DQ region remains the major determinant of susceptibility to type 1 diabetes (T1D) despite the more than 50 risk affecting loci outside human leukocyte antigen (HLA) region that have been identified. We aimed at developing a simple risk estimation based on HLA class II genotyping, which was also tested by analyzing HLA class II effect on the autoantibody seroconversion and further progression to diabetes. SUBJECTS AND METHODS: A total of 2991 trio families with a diabetic child from the Finnish Pediatric Diabetes Register were genotyped and the risk contributed by each DR-DQ haplotype calculated through transmission analysis...
July 2016: Pediatric Diabetes
https://www.readbyqxmd.com/read/27392045/double-blind-randomized-clinical-trial-gluten-versus-placebo-rechallenge-in-patients-with-lymphocytic-enteritis-and-suspected-celiac-disease
#19
Mercè Rosinach, Fernando Fernández-Bañares, Anna Carrasco, Montserrat Ibarra, Rocío Temiño, Antonio Salas, Maria Esteve
BACKGROUND: The role of gluten as a trigger of symptoms in non-coeliac gluten sensitivity has been questioned. AIM: To demonstrate that gluten is the trigger of symptoms in a subgroup of patients fulfilling the diagnostic criteria for non-coeliac gluten sensitivity (NCGS), which presented with lymphocytic enteritis, positive celiac genetics and negative celiac serology. METHODS: Double-blind randomized clinical trial of gluten vs placebo rechallenge...
2016: PloS One
https://www.readbyqxmd.com/read/27358913/single-cell-analysis-of-glandular-t-cell-receptors-in-sj%C3%A3-gren-s-syndrome
#20
Michelle L Joachims, Kerry M Leehan, Christina Lawrence, Richard C Pelikan, Jacen S Moore, Zijian Pan, Astrid Rasmussen, Lida Radfar, David M Lewis, Kiely M Grundahl, Jennifer A Kelly, Graham B Wiley, Mikhail Shugay, Dmitriy M Chudakov, Christopher J Lessard, Donald U Stone, R Hal Scofield, Courtney G Montgomery, Kathy L Sivils, Linda F Thompson, A Darise Farris
CD4(+) T cells predominate in salivary gland (SG) inflammatory lesions in Sjögren's syndrome (SS). However, their antigen specificity, degree of clonal expansion, and relationship to clinical disease features remain unknown. We used multiplex reverse-transcriptase PCR to amplify paired T cell receptor α (TCRα) and β transcripts of single CD4(+)CD45RA(-) T cells from SG and peripheral blood (PB) of 10 individuals with primary SS, 9 of whom shared the HLA DR3/DQ2 risk haplotype. TCRα and β sequences were obtained from a median of 91 SG and 107 PB cells per subject...
June 2, 2016: JCI Insight
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