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[PMID]:29383769
[Au] Autor:Oldenburger IB; Wolters VM; Kardol-Hoefnagel T; Houwen RHJ; Otten HG
[Ad] Endereço:Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, Utrecht, The Netherlands.
[Ti] Título:Serum intestinal fatty acid-binding protein in the noninvasive diagnosis of celiac disease.
[So] Source:APMIS;126(3):186-190, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Current diagnostic guidelines for celiac disease (CD) in pediatric patients require a duodenal biopsy if the IgA anti-tissue transglutaminase (tTG) is below 10x the upper limit of normal (ULN). Additional markers may enable a noninvasive diagnosis in this group. Serum intestinal-fatty acid-binding protein (I-FABP), a marker for intestinal epithelial damage, could be useful in this respect. A total of 95 children with a clinical suspicion of CD and tTG 1-10x ULN were investigated. All had a duodenal biopsy and analysis of serum I-FABP. A control group of 161 children with familial short stature and normal tTG was included. I-FABP levels in the 71 patients with tTG 1-10x ULN and biopsy-proven CD (median 725 pg/mL) were not significantly different (p = 0.13) from the levels in the 24 patients with a tTG 1-10x ULN but a normal biopsy (median 497 pg/mL). However, when combining tTG and I-FABP levels, 11/24 patients could have been diagnosed noninvasively if tTG is ≥ 50 U/mL and I-FABP ≥880 pg/mL or in 12/19 patients if tTG is ≥ 60 U/mL and I-FABP ≥ 620 pg/mL. Therefore, addition of I-FABP to the diagnostic procedure of CD may provide a noninvasive diagnosis in patients with a tTG ≥ 50 U/mL.
[Mh] Termos MeSH primário: Doença Celíaca/diagnóstico
Doença Celíaca/patologia
Proteínas de Ligação a Ácido Graxo/sangue
Proteínas de Ligação ao GTP/imunologia
Imunoglobulina A/sangue
Transglutaminases/imunologia
[Mh] Termos MeSH secundário: Adolescente
Doença Celíaca/sangue
Criança
Pré-Escolar
Duodeno/patologia
Proteínas de Ligação a Ácido Graxo/metabolismo
Feminino
Antígenos HLA-DQ/sangue
Seres Humanos
Imunoglobulina A/imunologia
Lactente
Mucosa Intestinal/patologia
Masculino
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (FABP2 protein, human); 0 (Fatty Acid-Binding Proteins); 0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DQ8 antigen); 0 (Immunoglobulin A); EC 2.3.2.- (transglutaminase 2); EC 2.3.2.13 (Transglutaminases); EC 2.3.2.13 (transglutaminase 1); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12800


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[PMID]:29372596
[Au] Autor:Villanacci V; Lorenzi L; Donato F; Auricchio R; Dziechciarz P; Gyimesi J; Koletzko S; Misak Z; Laguna VM; Polanco I; Ramos D; Shamir R; Troncone R; Vriezinga SL; Mearin ML
[Ad] Endereço:Institute of Pathology, ASST Spedali Civili di Brescia, Brescia, Italy.
[Ti] Título:Histopathological evaluation of duodenal biopsy in the PreventCD project. An observational interobserver agreement study.
[So] Source:APMIS;126(3):208-214, 2018 Mar.
[Is] ISSN:1600-0463
[Cp] País de publicação:Denmark
[La] Idioma:eng
[Ab] Resumo:Aim of the current study was to evaluate the inter-observer agreement between pathologists in the diagnosis of celiac disease (CD), in the qualified context of a multicenter study. Biopsies from the "PreventCD" study, a multinational- prospective- randomized study in children with at least one-first-degree relative with CD and positive for HLA-DQ2/HLA-DQ8. Ninety-eight biopsies were evaluated. Considering diagnostic samples with villous atrophy (VA), the agreement was satisfactory (κ = 0.84), but much less when assessing the severity of these lesions. The use of the recently proposed Corazza-Villanacci classification showed a moderately higher level of agreement (κ = 0.39) than using the Marsh-Oberhuber system (κ = 0.31). 57.1% of cases were considered correctly oriented. A number of >4 samples per patient was statistically associated to a better agreement; orientation did not impact on κ values. Agreement results in this study appear more satisfactory than in previous papers and this is justified by the involvement of centers with experience in CD diagnosis and by the well-controlled setting. Despite this, the reproducibility was far from optimal with a poor agreement in grading the severity of VA. Our results stress the need of a minimum of four samples to be assessed by the pathologist.
[Mh] Termos MeSH primário: Doença Celíaca/diagnóstico
Doença Celíaca/patologia
Antígenos HLA-DQ/imunologia
Mucosa Intestinal/patologia
[Mh] Termos MeSH secundário: Biópsia
Criança
Pré-Escolar
Duodeno/patologia
Seres Humanos
Lactente
Variações Dependentes do Observador
Estudos Prospectivos
Reprodutibilidade dos Testes
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DQ8 antigen)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1111/apm.12812


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[PMID]:29443768
[Au] Autor:Liu B; Deng T; Zhu L; Zhong J
[Ad] Endereço:Department of Ophthalmology, the First Affiliated Hospital of Jinan University.
[Ti] Título:Association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada disease: A systematic review and meta-analysis.
[So] Source:Medicine (Baltimore);97(7):e9914, 2018 Feb.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: The aim of this study was to evaluate the association of human leukocyte antigen (HLA)-DQ and HLA-DQA1/DQB1 alleles with Vogt-Koyanagi-Harada (VKH), providing further evidences on the genetic background of this disease. METHODS: A comprehensive literature search was conducted on the relationship of HLA-DQ and/or HLA-DQA1/DQB1 alleles with VKH through PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP, and databases for grey literature. The last search was in October 2017. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was calculated from extracted data to access the strength of the association between a genotype and VKH. RESULTS: HLA-DQ4 was confirmed to increase the risk of VKH significantly (OR = 4.63, 95% CI: 1.74-12.31, P = .002), while HLA-DQ1 seemed to reduce VKH occurrence with OR = 0.32 (95% CI: 0.22-0.47, P < .00001). HLA-DQA1*0301-(OR = 4.52, 95% CI: 1.42-14.35, P = .01) and HLA-DQB1*0401-(OR = 23.12, 95% CI: 11.54-46.31, P < .00001) positive patients probably had a rising tendency to suffer from VKH. Alleles including HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 were significant protective genetic factors. CONCLUSION: We concluded that HLA-DQ4 carriers had a higher risk of VKH and HLA-DQ1 seemed to be protective. People with positive HLA-DQA1*0301 and HLA-DQB1*0401 demonstrated to be more susceptible to VKH. HLA-DQA1*0103, 0401, 0501 and HLA-DQB1*0301, 0402, 0601, 0603 could be potential protectors.
[Mh] Termos MeSH primário: Antígenos HLA-DQ/genética
Cadeias alfa de HLA-DQ/genética
Cadeias beta de HLA-DQ/genética
Síndrome Uveomeningoencefálica/genética
[Mh] Termos MeSH secundário: Predisposição Genética para Doença
Seres Humanos
Fatores de Proteção
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (HLA-DQ Antigens); 0 (HLA-DQ alpha-Chains); 0 (HLA-DQ beta-Chains); 0 (HLA-DQ4 antigen); 0 (HLA-DQA1 antigen); 0 (HLA-DQB1 antigen)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:180215
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000009914


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[PMID]:28468970
[Au] Autor:Chowdhary VR; Krogman A; Tilahun AY; Alexander MP; David CS; Rajagopalan G
[Ad] Endereço:Division of Rheumatology, Department of Medicine, Mayo Clinic, Rochester, MN 55905.
[Ti] Título:Concomitant Disruption of and Genes Facilitates the Development of Double Negative αß TCR Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.
[So] Source:J Immunol;198(11):4413-4424, 2017 06 01.
[Is] ISSN:1550-6606
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mature peripheral double negative T (DNT) cells expressing αß TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated and genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors. Because HLA class II molecules present superantigens more efficiently than murine MHC class II molecules, CD4 CD8 double knockout (DKO) mice transgenically expressing HLA-DR3 or HLA-DQ8 molecules were generated. Although thymic cellularity was comparable between wild type (WT) and DKO mice, CD3 αß TCR thymocytes were significantly reduced in DKO mice, implying defects in thymic-positive selection. Splenic CD3 αß TCR cells and Foxp3 T regulatory cells were present in DKO mice but significantly reduced. However, the in vivo inflammatory responses and immunopathology elicited by acute challenge with the staphylococcal superantigen enterotoxin B were comparable between WT and DKO mice. Choric exposure to staphylococcal enterotoxin B precipitated a lupus-like inflammatory disease with characteristic lympho-monocytic infiltration in lungs, livers, and kidneys, along with production of anti-nuclear Abs in DKO mice as in WT mice. Overall, our results suggest that DNT cells can develop efficiently in vivo and chronic exposure to bacterial superantigens may precipitate a lupus-like autoimmune disease through activation of DNT cells.
[Mh] Termos MeSH primário: Antígenos CD4/genética
Antígenos CD4/imunologia
Antígenos CD8/genética
Antígenos CD8/imunologia
Enterotoxinas/imunologia
Superantígenos/imunologia
Subpopulações de Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Animais
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Antígeno HLA-DR3/genética
Antígeno HLA-DR3/imunologia
Antígenos de Histocompatibilidade Classe II/imunologia
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Receptores de Antígenos de Linfócitos T alfa-beta/genética
Receptores de Antígenos de Linfócitos T alfa-beta/imunologia
Baço/citologia
Baço/imunologia
Timo/citologia
Timo/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (CD4 Antigens); 0 (CD8 Antigens); 0 (Enterotoxins); 0 (HLA-DQ Antigens); 0 (HLA-DQ8 antigen); 0 (HLA-DR3 Antigen); 0 (Histocompatibility Antigens Class II); 0 (Receptors, Antigen, T-Cell, alpha-beta); 0 (Superantigens); 39424-53-8 (enterotoxin B, staphylococcal)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180127
[Lr] Data última revisão:
180127
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE
[do] DOI:10.4049/jimmunol.1601991


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[PMID]:28934241
[Au] Autor:Lundgren H; Martinsson K; Cederbrant K; Jirholt J; Mucs D; Madeyski-Bengtson K; Havarinasab S; Hultman P
[Ad] Endereço:Division of Molecular and Immunological Pathology, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, Östergötland County Council, Linköping, Sweden.
[Ti] Título:HLA-DR7 and HLA-DQ2: Transgenic mouse strains tested as a model system for ximelagatran hepatotoxicity.
[So] Source:PLoS One;12(9):e0184744, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The oral thrombin inhibitor ximelagatran was withdrawn in the late clinical trial phase because it adversely affected the liver. In approximately 8% of treated patients, drug-induced liver injury (DILI) was expressed as transient alanine transaminase (ALT) elevations. No evidence of DILI had been revealed in the pre-clinical in vivo studies. A whole genome scan study performed on the clinical study material identified a strong genetic association between the major histocompatibility complex alleles for human leucocyte antigens (HLA) (HLA-DR7 and HLA-DQ2) and elevated ALT levels in treated patients. An immune-mediated pathogenesis was suggested. Here, we evaluated whether HLA transgenic mice models could be used to investigate whether the expression of relevant HLA molecules was enough to reproduce the DILI effects in humans. In silico modelling performed in this study revealed association of both ximelagatran (pro-drug) and melagatran (active drug) to the antigen-presenting groove of the homology modelled HLA-DR7 molecule suggesting "altered repertoire" as a key initiating event driving development of DILI in humans. Transgenic mouse strains (tgms) expressing HLA of serotype HLA-DR7 (HLA-DRB1*0701, -DRA*0102), and HLA-DQ2 (HLA-DQB1*0202,-DQA1*0201) were created. These two lines were crossed with a human (h)CD4 transgenic line, generating the two tgms DR7xhCD4 and DQ2xhCD4. To investigate whether the DILI effects observed in humans could be reproduced in tgms, the mice were treated for 28 days with ximelagatran. Results revealed no signs of DILI when biomarkers for liver toxicity were measured and histopathology was evaluated. In the ximelagatran case, presence of relevant HLA-expression in a pre-clinical model did not fulfil the prerequisite for reproducing DILI observed in patients. Nonetheless, for the first time an HLA-transgenic mouse model has been investigated for use in HLA-associated DILI induced by a low molecular weight compound. This study shows that mimicking of genetic susceptibility, expressed as DILI-associated HLA-types in mice, is not sufficient for reproducing the complex pathogenesis leading to DILI in man.
[Mh] Termos MeSH primário: Azetidinas/toxicidade
Benzilaminas/toxicidade
Doença Hepática Induzida por Substâncias e Drogas
Modelos Animais de Doenças
Antígenos HLA-DQ
Antígeno HLA-DR7
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Doença Hepática Induzida por Substâncias e Drogas/imunologia
Feminino
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/metabolismo
Antígeno HLA-DR7/genética
Antígeno HLA-DR7/metabolismo
Seres Humanos
Linfócitos/metabolismo
Masculino
Camundongos Endogâmicos C57BL
Camundongos Transgênicos
Simulação de Acoplamento Molecular
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azetidines); 0 (Benzylamines); 0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DR7 Antigen); 49HFB70472 (ximelagatran)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171024
[Lr] Data última revisão:
171024
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170922
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184744


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[PMID]:28814219
[Au] Autor:Walker MM; Ludvigsson JF; Sanders DS
[Ad] Endereço:University of Newcastle, Newcastle, NSW marjorie.walker@newcastle.edu.au.
[Ti] Título:Coeliac disease: review of diagnosis and management.
[So] Source:Med J Aust;207(4):173-178, 2017 Aug 21.
[Is] ISSN:1326-5377
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:Coeliac disease is an immune-mediated systemic disease triggered by exposure to gluten, and manifested by small intestinal enteropathy and gastrointestinal and extra-intestinal symptoms. Recent guidelines recommend a concerted use of clear definitions of the disease. In Australia, the most recent estimated prevalence is 1.2% in adult men (1:86) and 1.9% in adult women (1:52). Active case finding is appropriate to diagnose coeliac disease in high risk groups. Diagnosis of coeliac disease is important to prevent nutritional deficiency and long term risk of gastrointestinal malignancy. The diagnosis of coeliac disease depends on clinico-pathological correlation: history, presence of antitransglutaminase antibodies, and characteristic histological features on duodenal biopsy (when the patient is on a gluten-containing diet). Human leucocyte antigen class II haplotypes DQ2 or DQ8 are found in nearly all patients with coeliac disease, but are highly prevalent in the general population at large (56% in Australia) and testing can only exclude coeliac disease for individuals with non-permissive haplotypes. Adhering to a gluten free diet allows duodenal mucosal healing and alleviates symptoms. Patients should be followed up with a yearly review of dietary adherence and a health check. Non-coeliac gluten or wheat protein sensitivity is a syndrome characterised by both gastrointestinal and extra-intestinal symptoms related to the ingestion of gluten and possibly other wheat proteins in people who do not have coeliac disease or wheat allergy recognised by diagnostic tests.
[Mh] Termos MeSH primário: Doença Celíaca/dietoterapia
Doença Celíaca/diagnóstico
Dieta Livre de Glúten
[Mh] Termos MeSH secundário: Adulto
Anticorpos/sangue
Austrália
Biomarcadores/sangue
Duodeno/patologia
Feminino
Antígenos HLA-DQ/genética
Seres Humanos
Mucosa Intestinal/patologia
Masculino
Guias de Prática Clínica como Assunto
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies); 0 (Biomarkers); 0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DQ8 antigen)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170818
[St] Status:MEDLINE


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[PMID]:28666081
[Au] Autor:Papalardo E; Romay-Penabad Z; Willis R; Christadoss P; Carrera-Marin AL; Reyes-Maldonado E; Rudrangi R; Alfieri-Papalardo S; Garcia-Latorre E; Blank M; Pierangeli S; Brasier AR; Gonzalez EB
[Ad] Endereço:University of Texas Medical Branch, Galveston.
[Ti] Título:Major Histocompatibility Complex Class II Alleles Influence Induction of Pathogenic Antiphospholipid Antibodies in a Mouse Model of Thrombosis.
[So] Source:Arthritis Rheumatol;69(10):2052-2061, 2017 Oct.
[Is] ISSN:2326-5205
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Both environmental and genetic factors are important in the development of antiphospholipid antibodies (aPL) in patients with antiphospholipid syndrome (APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiologic studies, without mechanistic evidence. Therefore, we studied the influence of major histocompatibility complex (MHC) class II alleles on the production of aPL in a mouse model of APS. METHODS: Three groups of mice, MHC class II-deficient (MHCII ) mice, MHCII mice transgenic for human HLA-DQ6 (DQ6), DQ8, or DR4 alleles, and the corresponding wild-type (WT) mouse strains were immunized; half were immunized with human ß -glycoprotein I (ß GPI), and the other half were immunized with control ovalbumin (OVA) protein. Thrombus formation in vivo, tissue factor activity in carotid and peritoneal macrophages, and serum levels of tumor necrosis factor (TNF), IgG anticardiolipin (aCL), antibodies, and anti-OVA antibodies were determined. RESULTS: Immunization with ß GPI induced significant production of aCL and anti-ß GPI in WT mice compared with control mice immunized with OVA (P < 0.001) but diminished aCL (P < 0.001) and anti-ß GPI (P = 0.016) production in MHCII mice. Anti-ß GPI production was fully restored in DQ6 and DQ8 mice, while levels of anti-ß GPI in DR4 mice and aCL in all transgenic lines were only partially restored (P < 0.001 to P < 0.046). Thrombus size in WT mice was twice that in MHCII mice (P < 0.001) but similar to that in all transgenic lines. Carotid and peritoneal macrophage tissue factor levels decreased by >50% in MHCII mice compared with wild-type B6 mice and were restored in DQ8 mice but not DR4 mice or DQ6 mice. TNF levels decreased 4-fold in MHCII mice (P < 0.001) and were not restored in transgenic mice. CONCLUSION: Our mechanistic study is the first to show that MHC class II alleles influence not only quantitative aPL production but also the pathogenic capacity of induced aPL.
[Mh] Termos MeSH primário: Anticorpos Antifosfolipídeos/imunologia
Genes MHC Classe II/genética
Antígenos HLA-DQ/genética
Antígeno HLA-DR4/genética
[Mh] Termos MeSH secundário: Alelos
Animais
Anticorpos Anticardiolipina/imunologia
Artérias Carótidas/imunologia
Modelos Animais de Doenças
Seres Humanos
Imunização
Imunoglobulina G/imunologia
Macrófagos/imunologia
Macrófagos Peritoneais/imunologia
Camundongos
Camundongos Knockout
Camundongos Transgênicos
Ovalbumina/imunologia
Índice de Gravidade de Doença
Trombose
Fator de Necrose Tumoral alfa/imunologia
beta 2-Glicoproteína I/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Anticardiolipin); 0 (Antibodies, Antiphospholipid); 0 (HLA-DQ Antigens); 0 (HLA-DQ6 antigen); 0 (HLA-DQ8 antigen); 0 (HLA-DR4 Antigen); 0 (Immunoglobulin G); 0 (Tumor Necrosis Factor-alpha); 0 (beta 2-Glycoprotein I); 9006-59-1 (Ovalbumin)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1002/art.40195


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[PMID]:28640108
[Au] Autor:Li Y; Huang Q; Tang JT; Wei TT; Yan L; Yang ZQ; Bai YJ; Wang LL; Shi YY
[Ad] Endereço:aDepartment of Laboratory Medicine, Division of Clinical Immunology, West China Hospital of Sichuan University bWest China School of Medicine, Sichuan University cDepartment of Nephrology, West China Hospital of Sichuan University, Chengdu, China.
[Ti] Título:Correlation of HLA-DP/DQ polymorphisms with transplant etiologies and prognosis in liver transplant recipients.
[So] Source:Medicine (Baltimore);96(25):e7205, 2017 Jun.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Previous study has identified that the genetic variants in the human leukocyte antigen (HLA)-DP/DQ region were strongly associated with hepatitis B virus (HBV) infection. But their roles in liver function recovery after hepatic transplantation were still obscure. This study aimed to investigate whether HLA-DP/DQ polymorphisms were associated with post-transplant etiologies and prognosis in Chinese liver transplant recipients.A total of 144 liver transplant recipients were enrolled, which were divided into 2 groups according to the transplant etiology: HBV-related disease and non-HBV-related disease. HBV-related disease includes 3 subgroups: liver cirrhosis, hepatocellular carcinoma, and progressive HBV hepatitis. Three single-nucleotide polymorphisms HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were studied in all recipients by high-resolution melting curve analysis. Liver function indices (albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, direct bilirubin, total bilirubin) and coagulation indices (prothrombin time, platelet, international normalized ratio, fibrinogen) were routinely tested. After transplant, 10 recipients who were positive for HBsAg or with elevation in HBV virus load were regarded as HBV recurrence.No significant association of HLA-DP/DQ polymorphisms with HBV recurrence or transplant etiology was observed (P < .05). Recipients with HLA-DQ (rs7453920) AG and AA genotype had lower direct bilirubin levels than GG genotype individuals, especially on the 14th day after surgery (17.80 vs. 5.35, P  =  .038). Patients with A alleles displayed earlier liver function recovery than patients with G alleles (7 vs. 6 months). No significant correlation was shown in HLA-DP rs3077 and rs9277535 with HBV infection or liver function recovery (P < .05).Our study concluded that HLA-DP (rs3077 and rs9277535) and HLA-DQ (rs7453920) were not significantly associated with HBV recurrence or HBV susceptibility, but HLA-DQ rs7453920 was related to prognosis of liver transplant recipients. HLA-DQ rs7453920 A might be used as an indicator of earlier recovery and better prognosis after transplantation.
[Mh] Termos MeSH primário: Antígenos HLA-DP/genética
Antígenos HLA-DQ/genética
Hepatopatias/genética
Hepatopatias/cirurgia
Transplante de Fígado
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
Feminino
Estudos de Associação Genética
Predisposição Genética para Doença
Técnicas de Genotipagem
Hepatite B/genética
Hepatite B/cirurgia
Vírus da Hepatite B
Seres Humanos
Hepatopatias/etiologia
Hepatopatias/virologia
Masculino
Meia-Idade
Prognóstico
Recidiva
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (HLA-DP Antigens); 0 (HLA-DQ Antigens)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170717
[Lr] Data última revisão:
170717
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170623
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007205


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[PMID]:28624578
[Au] Autor:Werkstetter KJ; Korponay-Szabó IR; Popp A; Villanacci V; Salemme M; Heilig G; Lillevang ST; Mearin ML; Ribes-Koninckx C; Thomas A; Troncone R; Filipiak B; Mäki M; Gyimesi J; Najafi M; Dolinsek J; Dydensborg Sander S; Auricchio R; Papadopoulou A; Vécsei A; Szitanyi P; Donat E; Nenna R; Alliet P; Penagini F; Garnier-Lengliné H; Castillejo G; Kurppa K; Shamir R; Hauer AC; Smets F; Corujeira S; van Winckel M; Buderus S; Chong S; Husby S; Koletzko S; ProCeDE study group
[Ad] Endereço:Dr. von Hauner Children's Hospital, Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany.
[Ti] Título:Accuracy in Diagnosis of Celiac Disease Without Biopsies in Clinical Practice.
[So] Source:Gastroenterology;153(4):924-935, 2017 Oct.
[Is] ISSN:1528-0012
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND & AIMS: The guidelines of the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition allow for diagnosis of celiac disease without biopsies in children with symptoms and levels of immunoglobulin A against tissue-transglutaminase (TGA-IgA) 10-fold or more the upper limit of normal (ULN), confirmed by detection of endomysium antibodies (EMA) and positivity for HLA-DQ2/DQ8. We performed a large, international prospective study to validate this approach. METHODS: We collected data from consecutive pediatric patients (18 years or younger) on a gluten-containing diet who tested positive for TGA-IgA from November 2011 through May 2014, seen at 33 pediatric gastroenterology units in 21 countries. Local centers recorded symptoms; measurements of total IgA, TGA, and EMA; and histopathology findings from duodenal biopsies. Children were considered to have malabsorption if they had chronic diarrhea, weight loss (or insufficient gain), growth failure, or anemia. We directly compared central findings from 16 antibody tests (8 for TGA-IgA, 1 for TGA-IgG, 6 for IgG against deamidated gliadin peptides, and 1 for EMA, from 5 different manufacturers), 2 HLA-DQ2/DQ8 tests from 2 manufacturers, and histopathology findings from the reference pathologist. Final diagnoses were based on local and central results. If all local and central results were concordant for celiac disease, cases were classified as proven celiac disease. Patients with only a low level of TGA-IgA (threefold or less the ULN) but no other results indicating celiac disease were classified as no celiac disease. Central histo-morphometry analyses were performed on all other biopsies and cases were carefully reviewed in a blinded manner. Inconclusive cases were regarded as not having celiac disease for calculation of diagnostic accuracy. The primary aim was to determine whether the nonbiopsy approach identifies children with celiac disease with a positive predictive value (PPV) above 99% in clinical practice. Secondary aims included comparing performance of different serological tests and to determine whether the suggested criteria can be simplified. RESULTS: Of 803 children recruited for the study, 96 were excluded due to incomplete data, low level of IgA, or poor-quality biopsies. In the remaining 707 children (65.1% girls; median age, 6.2 years), 645 were diagnosed with celiac disease, 46 were found not to have celiac disease, and 16 had inconclusive results. Findings from local laboratories of TGA-IgA 10-fold or more the ULN, a positive result from the test for EMA, and any symptom identified children with celiac disease (n = 399) with a PPV of 99.75 (95% confidence interval [CI], 98.61-99.99); the PPV was 100.00 (95% CI, 98.68-100.00) when only malabsorption symptoms were used instead of any symptom (n = 278). Inclusion of HLA analyses did not increase accuracy. Findings from central laboratories differed greatly for patients with lower levels of antibodies, but when levels of TGA-IgA were 10-fold or more the ULN, PPVs ranged from 99.63 (95% CI, 98.67-99.96) to 100.00 (95% CI, 99.23-100.00). CONCLUSIONS: Children can be accurately diagnosed with celiac disease without biopsy analysis. Diagnosis based on level of TGA-IgA 10-fold or more the ULN, a positive result from the EMA tests in a second blood sample, and the presence of at least 1 symptom could avoid risks and costs of endoscopy for more than half the children with celiac disease worldwide. HLA analysis is not required for accurate diagnosis. Clinical Trial Registration no: DRKS00003555.
[Mh] Termos MeSH primário: Autoanticorpos/sangue
Doença Celíaca/diagnóstico
Doença Celíaca/imunologia
Proteínas de Ligação ao GTP/imunologia
Imunoglobulina A/sangue
Intestino Delgado/imunologia
Transglutaminases/imunologia
[Mh] Termos MeSH secundário: Adolescente
Biomarcadores/sangue
Biópsia
Doença Celíaca/sangue
Doença Celíaca/genética
Criança
Pré-Escolar
Europa (Continente)
Feminino
Antígenos HLA-DQ/genética
Antígenos HLA-DQ/imunologia
Seres Humanos
Lactente
Intestino Delgado/patologia
Masculino
Oriente Médio
Técnicas de Diagnóstico Molecular
Valor Preditivo dos Testes
Prognóstico
Estudos Prospectivos
Reprodutibilidade dos Testes
Testes Sorológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Autoantibodies); 0 (Biomarkers); 0 (HLA-DQ Antigens); 0 (HLA-DQ2 antigen); 0 (HLA-DQ8 antigen); 0 (Immunoglobulin A); EC 2.3.2.- (transglutaminase 2); EC 2.3.2.13 (Transglutaminases); EC 3.6.1.- (GTP-Binding Proteins)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170619
[St] Status:MEDLINE


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[PMID]:28613373
[Au] Autor:Pereira VRZB; Wolf JM; Stumm GZ; Boeira TR; Galvan J; Simon D; Lunge VR
[Ad] Endereço:, , Brasil.
[Ti] Título:Lack of association between human leukocyte antigen polymorphisms rs9277535 and rs7453920 and chronic hepatitis B in a Brazilian population.
[So] Source:Genet Mol Res;16(2), 2017 May 31.
[Is] ISSN:1676-5680
[Cp] País de publicação:Brazil
[La] Idioma:eng
[Ab] Resumo:Hepatitis B virus (HBV) infection is a serious public health problem worldwide. The progression of the disease depends on several host and viral factors and may result in fulminant hepatitis (very rare), acute hepatitis with spontaneous clearance, and chronic hepatitis B infection. Previous studies demonstrated that variations in the human leukocyte antigen (HLA) class II (HLA-DPB1 and HLA-DQB2 genes) are related to the chronic HBV infection. This study aimed to investigate the association of two single nucleotide polymorphism (SNPs), one in the HLA-DPB1 (rs9277535) and one in the HLA-DQB2 (rs7453920), with chronic hepatitis B infection in a southern Brazilian sample. This case-control study included 260 HBV patients attended in a Specialized Center for Health in Caxias do Sul (Brazil) between 2014 and 2016. The same number of controls (matching for age, gender, and ethnicity) was obtained in a University Hospital in the same city and period. Blood samples were collected and genomic DNA was extracted. Genotyping were performed by real-time Taqman PCR method. Odds ratios with 95% confidence intervals and significance level of 5% (P < 0.05) were calculated. Allele frequencies in the SNP rs9277535 were 72.6% for A and 27.4% for G nucleotides in cases and 75.0% for A and 25.0% for G in controls. Allele frequencies in the SNP rs7453920 were of 25.7% for A and 74.3% for G in cases and 28.8% for A and 71.2% for G in controls. No statistically significant association was found between both SNPs and chronic hepatitis B (P > 0.05).
[Mh] Termos MeSH primário: Cadeias beta de HLA-DP/genética
Antígenos HLA-DQ/genética
Hepatite B Crônica/genética
Polimorfismo de Nucleotídeo Único
[Mh] Termos MeSH secundário: Adulto
Brasil
Estudos de Casos e Controles
Feminino
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HLA-DP beta-Chains); 0 (HLA-DPB1 antigen); 0 (HLA-DQ Antigens); 0 (HLA-Dx antigen)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171006
[Lr] Data última revisão:
171006
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170615
[St] Status:MEDLINE
[do] DOI:10.4238/gmr16029565



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