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https://www.readbyqxmd.com/read/27913849/targeted-next-generation-sequencing-reveals-mody-in-up-to-6-5-of-antibody-negative-diabetes-cases-listed-in-the-norwegian-childhood-diabetes-registry
#1
Bente B Johansson, Henrik U Irgens, Janne Molnes, Paweł Sztromwasser, Ingvild Aukrust, Petur B Juliusson, Oddmund Søvik, Shawn Levy, Torild Skrivarhaug, Geir Joner, Anders Molven, Stefan Johansson, Pål R Njølstad
AIMS/HYPOTHESIS: MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes. METHODS: Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children)...
December 2, 2016: Diabetologia
https://www.readbyqxmd.com/read/27913750/congenital-heart-block-and-immune-mediated-sensorineural-hearing-loss-possible-cross-reactivity-of-immune-response
#2
C Bason, I Pagnini, A Brucato, S Maestroni, A Puccetti, C Lunardi, R Cimaz
Immune-mediated sensorineural hearing loss may complicate systemic autoimmune diseases. We have previously reported the presence of antibodies directed against inner ear antigens in patients with Cogan syndrome, a disease characterized by sudden hearing loss and interstitial keratitis. Such autoantibodies cross-react with an epitope of SSA/Ro60 protein. Anti-Ro/SSA antibodies in pregnant women cross the placenta and reach the fetal tissues inducing an immune-mediated damage of the cardiac conduction system...
December 2, 2016: Lupus
https://www.readbyqxmd.com/read/27913646/critical-differences-between-induced-and-spontaneous-mouse-models-of-graves-disease-with-implications-for-antigen-specific-immunotherapy-in-humans
#3
Basil Rapoport, Bianca Banuelos, Holly A Aliesky, Nicole Hartwig Trier, Sandra M McLachlan
Graves' hyperthyroidism, a common autoimmune disease caused by pathogenic autoantibodies to the thyrotropin (TSH) receptor (TSHR), can be treated but not cured. This single autoantigenic target makes Graves' disease a prime candidate for Ag-specific immunotherapy. Previously, in an induced mouse model, injecting TSHR A-subunit protein attenuated hyperthyroidism by diverting pathogenic TSHR Abs to a nonfunctional variety. In this study, we explored the possibility of a similar diversion in a mouse model that spontaneously develops pathogenic TSHR autoantibodies, NOD...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913645/iga-complexes-in-plasma-and-synovial-fluid-of-patients-with-rheumatoid-arthritis-induce-neutrophil-extracellular-traps-via-fc%C3%AE-ri
#4
Esil Aleyd, Marjon Al, Cornelis W Tuk, Conny J van der Laken, Marjolein van Egmond
Autoantibodies, including rheumatoid factor (RF), are an important characteristic of rheumatoid arthritis (RA). Interestingly, several studies reported a correlation between the presence of IgA autoantibodies and worse disease course. We demonstrated previously that triggering the IgA Fc receptor (FcαRI) on neutrophils results in neutrophil recruitment and the release of neutrophil extracellular traps (NETs). Because this can lead to tissue damage, we investigated whether IgA immune complexes in plasma and synovial fluid of RA patients activate neutrophils...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913607/autoimmune-comorbidities-in-hashimoto-s-thyroiditis-different-patterns-of-association-in-adulthood-and-childhood-adolescence
#5
R M Ruggeri, F Trimarchi, G Giuffrida, R Certo, E Cama, A Campennì, A Alibrandi, F De Luca, M Wasniewska
OBJECTIVE: Hashimoto's thyroiditis (HT), the most common autoimmune thyroid disease at any age, is often associated with other autoimmune diseases. The present study was aimed to describe the type and frequency of non-thyroidal autoimmune diseases (NTADs) in HT patients and to delineate the clinical pattern of diseases clustering in pediatric/adolescent and adult age. DESIGN: Cross-sectional study. METHODS: 1053 newly diagnosed HT patients (500 adults (467 F, mean age 40...
February 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27913548/warm-antibody-autoimmune-hemolytic-anemia
#6
Theodosia A Kalfa
Autoimmune hemolytic anemia (AIHA) is a rare and heterogeneous disease that affects 1 to 3/100 000 patients per year. AIHA caused by warm autoantibodies (w-AIHA), ie, antibodies that react with their antigens on the red blood cell optimally at 37°C, is the most common type, comprising ∼70% to 80% of all adult cases and ∼50% of pediatric cases. About half of the w-AIHA cases are called primary because no specific etiology can be found, whereas the rest are secondary to other recognizable underlying disorders...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27912793/antibodies-against-carbamylated-proteins-and-cyclic-citrullinated-peptides-in-systemic-lupus-erythematosus-results-from-two-well-defined-european-cohorts
#7
Michael Ziegelasch, Myrthe A M van Delft, Philip Wallin, Thomas Skogh, César Magro-Checa, Gerda M Steup-Beekman, Leendert A Trouw, Alf Kastbom, Christopher Sjöwall
BACKGROUND: Articular manifestations are common in systemic lupus erythematosus (SLE) whereas erosive disease is not. Antibodies to cyclic citrullinated peptide (anti-CCP) are citrulline-dependent in rheumatoid arthritis (RA), whereas the opposite is suggested in SLE, as reactivity with cyclic arginine peptide (CAP) is typically present. Antibodies targeting carbamylated proteins (anti-CarP) may occur in anti-CCP/rheumatoid factor (RF)-negative cases long before clinical onset of RA. We analysed these antibody specificities in sera from European patients with SLE in relation to phenotypes, smoking habits and imaging data...
December 3, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27911796/egr2-and-egr3-in-regulatory-t-cells-cooperatively-control-systemic-autoimmunity-through-ltbp3-mediated-tgf-%C3%AE-3-production
#8
Kaoru Morita, Tomohisa Okamura, Mariko Inoue, Toshihiko Komai, Shuzo Teruya, Yukiko Iwasaki, Shuji Sumitomo, Hirofumi Shoda, Kazuhiko Yamamoto, Keishi Fujio
Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by multiorgan inflammation induced by autoantibodies. Early growth response gene 2 (Egr2), a transcription factor essential for T-cell anergy induction, controls systemic autoimmunity in mice and humans. We have previously identified a subpopulation of CD4(+) regulatory T cells, CD4(+)CD25(-)LAG3(+) cells, that characteristically express both Egr2 and LAG3 and control mice model of lupus via TGF-β3 production. However, due to the mild phenotype of lymphocyte-specific Egr2-deficient mice, the presence of an additional regulator has been speculated...
November 30, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911591/type-b-insulin-resistance-masquerading-as-ovarian-hyperthecosis
#9
Rebecca J Brown, Jalaja Joseph, Elaine Cochran, Cornelia Gewert, Robert Semple, Phillip Gorden
CONTEXT: Hyperinsulinemia can lead to pathologic ovarian growth and androgen production. CASE DESCRIPTION: A 29 year old woman developed an autoantibody to the insulin receptor (Type B insulin resistance), causing extreme insulin resistance and hyperinsulinemia. Testosterone levels were elevated to the adult male range. Treatment with gonadotropin releasing hormone (GnRH) analog led to normalization of testosterone, despite persistent extreme insulin resistance...
December 2, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27909160/evaluation-of-polymorphic-variants-in-apoptotic-genes-and-their-role-in-susceptibility-and-clinical-progression-to-systemic-lupus-erythematosus
#10
N Glesse, P Vianna, L M G Paim, M C C Matte, A K K Aguiar, P L Palhano, O A Monticielo, C V Brenol, R M Xavier, J A B Chies
BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes...
November 30, 2016: Lupus
https://www.readbyqxmd.com/read/27909085/a-negative-antinuclear-antibody-does-not-indicate-autoantibody-negativity-in-myositis-role-of-anticytoplasmic-antibody-as-a-screening-test-for-antisynthetase-syndrome
#11
Rohit Aggarwal, Namrata Dhillon, Noreen Fertig, Diane Koontz, Zengbiao Qi, Chester V Oddis
OBJECTIVE: To evaluate the utility of anticytoplasmic autoantibody (anti-CytAb) in antisynthetase antibody-positive (anti-SynAb+) patients. METHODS: Anti-SynAb+ patients were evaluated for antinuclear antibody (ANA) and anti-CytAb [cytoplasmic staining on indirect immunofluorescence (IIF)] positivity. Anti-SynAb+ patients included those possessing anti-Jo1 and other antisynthetase autoantibodies. Control groups included scleroderma, systemic lupus erythematosus, Sjögren syndrome, rheumatoid arthritis, and healthy subjects...
December 1, 2016: Journal of Rheumatology
https://www.readbyqxmd.com/read/27908533/relevance-of-antiphospholipid-antibodies-in-multiple-sclerosis-a-systematic-review-and-meta-analysis
#12
Mira Merashli, Jose Delgado Alves, Fabrizio Gentile, Paul R J Ames
BACKGROUND: The relationship between antiphospholipid antibodies (aPL) and multiple sclerosis (MS) is unclear. OBJECTIVES: To evaluate a link between aPL and MS. METHODS: EMBASE and PubMed search to August 2016; Peto's odds ratio (OR) meta-analysis. RESULTS: The pooled prevalence of participants positive for IgG and IgM anticardiolipin (aCL) from 12 case-control studies was superior in MS than controls (6.8% vs 1.8%, p = 0...
October 3, 2016: Seminars in Arthritis and Rheumatism
https://www.readbyqxmd.com/read/27908303/dna-damage-increase-in-peripheral-neutrophils-from-patients-with-rheumatoid-arthritis-is-associated-with-the-disease-activity-and-the-presence-of-shared-epitope
#13
Gustavo Martelli-Palomino, Adriana B Paoliello-Paschoalato, Janaina C O Crispim, Diane M Rassi, Rene D Oliveira, Paulo Louzada, Yara Maria Lucisano-Valim, Eduardo A Donadi
OBJECTIVES: Neutrophils play a major role in rheumatoid arthritis (RA) pathogenesis. We aimed to evaluate if neutrophil DNA damage in RA patients is associated with the disease activity, autoantibodies status, carriage of the RA shared epitope (SE) and treatment. METHODS: DNA damage was assessed by alkaline comet assay in peripheral blood (77 patients and 55 healthy controls) and in 10 RA synovial fluid neutrophils. Evaluation of the respiratory burst of 30 patients with RA and 30 healthy controls was done...
November 14, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27907006/prediction-of-impending-type-1-diabetes-through-automated-dual-label-measurement-of-proinsulin-c-peptide-ratio
#14
Annelien Van Dalem, Simke Demeester, Eric V Balti, Bart Keymeulen, Pieter Gillard, Bruno Lapauw, Christophe De Block, Pascale Abrams, Eric Weber, Ilse Vermeulen, Pieter De Pauw, Daniël Pipeleers, Ilse Weets, Frans K Gorus
BACKGROUND: The hyperglycemic clamp test, the gold standard of beta cell function, predicts impending type 1 diabetes in islet autoantibody-positive individuals, but the latter may benefit from less invasive function tests such as the proinsulin:C-peptide ratio (PI:C). The present study aims to optimize precision of PI:C measurements by automating a dual-label trefoil-type time-resolved fluorescence immunoassay (TT-TRFIA), and to compare its diagnostic performance for predicting type 1 diabetes with that of clamp-derived C-peptide release...
2016: PloS One
https://www.readbyqxmd.com/read/27906181/stat6-deficiency-ameliorates-graves-disease-severity-by-suppressing-thyroid-epithelial-cell-hyperplasia
#15
Xuechao Jiang, Bingbing Zha, Xiaoming Liu, Ronghua Liu, Jun Liu, Enyu Huang, Tingting Qian, Jiajing Liu, Zhiming Wang, Dan Zhang, Luman Wang, Yiwei Chu
Signal transducer and activator of transcription 6 (STAT6) is involved in epithelial cell growth. However, little is known regarding the STAT6 phosphorylation status in Graves' disease (GD) and its role in thyroid epithelial cells (TECs). In this study, we found that STAT6 phosphorylation (p-STAT6) was significantly increased in TECs from both GD patients and experimental autoimmune Graves' disease mice and that STAT6 deficiency ameliorated GD symptoms. Autocrine IL-4 signalling in TECs activated the phosphorylation of STAT6 via IL-4 R engagement, and the downstream targets of STAT6 were Bcl-xL and cyclin D1...
December 1, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27906052/antibody-responses-to-de-novo-identified-citrullinated-fibrinogen-peptides-in-rheumatoid-arthritis-and-visualization-of-the-corresponding-b-cells
#16
Vijay Joshua, Loes Schobers, Philip J Titcombe, Lena Israelsson, Johan Rönnelid, Monika Hansson, Anca I Catrina, Ger J M Pruijn, Vivianne Malmström
BACKGROUND: Antibodies against citrullinated proteins (ACPA) are common in patients with rheumatoid arthritis (RA). ACPA can appear before disease onset and target many self-antigens. Citrullinated fibrin/fibrinogen represents a classical ACPA target antigen, and mass spectrometry of RA synovial fluid reveals elevated citrullinated (cit) fibrinogen (Fib) peptides compared to non-RA controls. We investigated the extent to which these less-studied peptides represent autoantibody targets and sought to visualize the corresponding cit-Fib-reactive B cells in RA patients...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27906045/smoking-is-associated-with-the-concurrent-presence-of-multiple-autoantibodies-in-rheumatoid-arthritis-rather-than-with-anti-citrullinated-protein-antibodies-per-se-a-multicenter-cohort-study
#17
Tineke J van Wesemael, Sofia Ajeganova, Jennifer Humphreys, Chikashi Terao, Ammar Muhammad, Deborah P M Symmons, Alex J MacGregor, Ingiäld Hafström, Leendert A Trouw, Annette H M van der Helm-van Mil, Tom W J Huizinga, Tsuneyo Mimori, René E M Toes, Fumihiko Matsuda, Björn Svensson, Suzanne M M Verstappen, Diane van der Woude
BACKGROUND: The contribution of smoking to rheumatoid arthritis (RA) is hypothesized to be mediated through formation of anti-citrullinated protein antibodies (ACPA). In RA, however, autoantibodies such as ACPA, rheumatoid factor (RF), and anti-carbamylated protein antibodies (anti-CarP) often occur together, and it is thus unclear whether smoking is specifically associated with some autoantibodies rather than others. We therefore investigated whether smoking is only associated with ACPA or with the presence of multiple RA-related autoantibodies...
December 1, 2016: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/27905992/variable-sensitivity-to-complement-dependent-cytotoxicity-in-murine-models-of-neuromyelitis-optica
#18
Yiting Liu, Danielle E Harlow, Katherine S Given, Gregory P Owens, Wendy B Macklin, Jeffrey L Bennett
BACKGROUND: Studies of neuromyelitis optica (NMO), an autoimmune disease of the central nervous system (CNS), have demonstrated that autoantibodies against the water channel aquaporin-4 (AQP4) induce astrocyte damage through complement-dependent cytotoxicity (CDC). In developing experimental models of NMO using cells, tissues or animals from mice, co-administration of AQP4-IgG and normal human serum, which serves as the source of human complement (HC), is required. The sensitivity of mouse CNS cells to HC and CDC in these models is not known...
December 1, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27905968/monitoring-the-prevalence-of-thyroid-disorders-in-the-adult-population-of-northeast-germany
#19
Rehman Mehmood Khattak, Till Ittermann, Matthias Nauck, Harald Below, Henry Völzke
BACKGROUND: Only a few studies like ours have investigated the effect of long-term stable iodine supply on thyroid disorders in a historically iodine-deficient population, but not with a long follow-up time of 10 years. METHODS: Data were derived from two independent population-based cohorts of the Study of Health in Pomerania (SHIP-0 [1997-2001] and SHIP-TREND [2008-2012]) comprising 4308 and 4420 subjects, respectively. Diagnosed thyroid disorders were assessed...
November 8, 2016: Population Health Metrics
https://www.readbyqxmd.com/read/27905032/characteristics-of-lipoprotein-a-containing-circulating-immune-complexes-as-markers-of-coronary-heart-disease
#20
E A Klesareva, O I Afanas'eva, V V Donskikh, I Yu Adamova, S N Pokrovskii
We studied the composition of circulating immune complexes precipitated in the presence of various concentrations of polyethylene glycol in patients with coronary heart disease (CHD) and high concentration of lipoprotein(a) - Lp(a). Precipitation of highly purified Lp(a) preparation with polyethylene glycol was evaluated. The contents of Lp(a), autoantibodies to Lp(a), IgG, and IgM in circulating immune complexes isolated from the sera of donors and CHD patients with normal and high levels of Lp(a) were measured...
December 1, 2016: Bulletin of Experimental Biology and Medicine
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