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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/29331322/expression-level-of-risk-genes-of-mhc-class-ii-is-a-susceptibility-factor-for-autoimmunity-new-insights
#1
REVIEW
Carmen Gianfran, Laura Pisapia, Stefania Picascia, Maria Strazzullo, Giovanna Del Pozzo
To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and proliferation of autoantigen-reactive T cells...
January 10, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29310926/identification-of-non-hla-genes-associated-with-development-of-islet-autoimmunity-and-type-1-diabetes-in-the-prospective-teddy-cohort
#2
Ashok Sharma, Xiang Liu, David Hadley, William Hagopian, Wei-Min Chen, Suna Onengut-Gumuscu, Carina Törn, Andrea K Steck, Brigitte I Frohnert, Marian Rewers, Anette-G Ziegler, Åke Lernmark, Jorma Toppari, Jeffrey P Krischer, Beena Akolkar, Stephen S Rich, Jin-Xiong She
Traditional linkage analysis and genome-wide association studies have identified HLA and a number of non-HLA genes as genetic factors for islet autoimmunity (IA) and type 1 diabetes (T1D). However, the relative risk associated with previously identified non-HLA genes is usually very small as measured in cases/controls from mixed populations. Genetic associations for IA and T1D may be more accurately assessed in prospective cohorts. In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip...
January 5, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29310925/th17-lineage-cells-in-pulmonary-sarcoidosis-and-l%C3%A3-fgren-s-syndrome-friend-or-foe
#3
REVIEW
Jelle R Miedema, Ylva Kaiser, Caroline E Broos, Marlies S Wijsenbeek, Johan Grunewald, Mirjam Kool
Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressive mechanisms may account for differences in clinical presentation as well as prognosis compared to non-LS sarcoidosis...
January 5, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29307589/pathogenic-igg4-autoantibodies-from-endemic-pemphigus-foliaceus-recognize-a-desmoglein-1-conformational-epitope
#4
Flor Evangelista, Aleeza J Roth, Phillip Prisayanh, Brenda R Temple, Ning Li, Ye Qian, Donna A Culton, Zhi Liu, Oliver J Harrison, Julia Brasch, Barry Honig, Lawrence Shapiro, Luis A Diaz
Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A129LNSMGQDLERPLELR144) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule...
January 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29307588/autoantibodies-against-podocytic-uchl1-are-associated-with-idiopathic-nephrotic-syndrome-relapses-and-induce-proteinuria-in-mice
#5
Agnès Jamin, Laureline Berthelot, Anne Couderc, Jonathan M Chemouny, Erwan Boedec, Laurène Dehoux, Lilia Abbad, Claire Dossier, Eric Daugas, Renato C Monteiro, Georges Deschênes
Idiopathic steroid sensitive nephrotic syndrome (INS), the most frequent childhood nephropathy, is thought to be mediated by a circulating soluble factor that reversibly affects the renal protein sieving. The efficiency of rituximab therapy recently highlighted the involvement of B cells. Here we studied the involvement of a specific immunoglobulin G (IgG) in the disease. After plasma fractionation by size exclusion chromatography, a detachment of cultured podocyte was observed with one IgG-containing fraction from 47% patients in relapse, 9% of patients in remission and 0% of controls...
January 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29307587/cd8-t-cells-and-ifn-%C3%AE-induce-autoimmune-myelofibrosis-in-mice
#6
Yuan Yao, Liang Li, Shu-Han Yang, Cai-Yue Gao, Liang-Huan Liao, Yu-Qing Xie, Xue-Ying Yin, Yan-Qing Yang, Yun-Yun Fei, Zhe-Xiong Lian
Myelofibrosis usually occurs either as a part of a myelodysplastic syndrome or in conjunction with neoplasia. It is not commonly thought of an autoimmune disease. We reported that p40-/-IL-2Rα-/- (interleukin-12p40 and interleukin-2 receptor alpha double knockout) mice, a mouse model of human primary biliary cholangitis, exhibited features consistent with autoimmune myelofibrosis, including anemia associated with bone marrow fibrosis, and extramedullary hematopoiesis (EMH) including LSK (Lineage-c-Kit+Sca-1+) cells in spleen, liver and peripheral blood...
January 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29290521/th17-plasticity-and-its-relevance-to-inflammatory-bowel-disease
#7
REVIEW
Aito Ueno, Louisa Jeffery, Taku Kobayashi, Toshifumi Hibi, Subrata Ghosh, Humberto Jijon
It is now clear that previously polarized T cells possess the ability to change their phenotype and repolarize towards different fates. This intrinsic flexibility is commonly referred to as plasticity and is influenced by the cytokine milieu, microbial products and products of metabolism which, in turn, regulate transcription factors and epigenetic machinery in the intestinal lamina propria. The intestinal immune system faces a particularly difficult challenge. It serves to protect the largest mucosal surface against infection and injury while maintaining a state of tolerance towards dietary antigens and the largest population of commensal organisms in the body...
December 28, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29275837/plasticity-and-heterogeneity-of-th17-in-immune-mediated-kidney-diseases
#8
REVIEW
Christian F Krebs, Ulf Panzer
Anti-neutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis, anti-glomerular basement membrane (GBM) glomerulonephritis and lupus nephritis are the most common causes of rapid progressive glomerulonephritis (RPGN) in the Western world. These aggressive forms of autoimmune kidney diseases significantly contribute to end-stage renal disease and are associated with high morbidity and mortality. Moreover, patients show significant heterogeneity with respect to clinical outcome and response to therapy...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29275836/a-cellular-and-molecular-view-of-t-helper-17%C3%A2-cell-plasticity-in-autoimmunity
#9
REVIEW
Ralph Stadhouders, Erik Lubberts, Rudi W Hendriks
Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and plasticity. This has been attributed to the characteristics of the key transcription factor that guides Th17 differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ)...
December 21, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29269245/critical-role-of-rock2-activity-in-facilitating-mucosal-cd4-t-cell-activation-in-inflammatory-bowel-disease
#10
Wenjing Yang, Guangxi Zhou, Tianming Yu, Liang Chen, Lin Yu, Yanmin Guo, Yingzi Cong, Zhanju Liu
Rho-associated kinase (ROCK) has been found to be involved in the pathogenesis of a variety of autoimmune diseases, but the role of ROCK in inflammatory bowel disease (IBD) is still elusive. In this study, we demonstrated that the levels of ROCK2, but not ROCK1, activity were significantly upregulated in peripheral blood mononuclear cells (PBMC) and inflamed mucosa from IBD patients using a ROCK activity assay, and that ROCK2 activity in intestinal mucosa was positively correlated with disease severity. Stimulation with TNF markedly upregulated ROCK2 activity in IBD CD4+ T cells through NF-κB signaling...
December 19, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29258717/tolerogenic-ag-plg-nanoparticles-induce-tregs-to-suppress-activated-diabetogenic-cd4-and-cd8-t-cells
#11
Suchitra Prasad, Tobias Neef, Dan Xu, Joseph R Podojil, Daniel R Getts, Lonnie D Shea, Stephen D Miller
Type 1 diabetes (T1D) is mediated by destruction of pancreatic β cells by autoantigen-specific CD4+ and CD8+ T cells, thus the ideal solution for T1D is the restoration of immune tolerance to β cell antigens. We demonstrate the ability of carboxylated 500 nm biodegradable poly(lactide-co-glycolide) (PLG) nanoparticles PLG nanoparticles (either surface coupled with or encapsulating the cognate diabetogenic peptides) to rapidly and efficiently restore tolerance in NOD.SCID recipients of both activated diabetogenic CD4+ BDC2...
December 16, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29254845/molecular-mechanisms-underpinning-t-helper-17-cell-heterogeneity-and-functions-in-rheumatoid-arthritis
#12
REVIEW
Jan Piet van Hamburg, Sander W Tas
T helper 17 (Th17) cells are important mediators of immune responses against extracellular bacteria and fungi, and as such play critical regulatory roles in maintaining mucosal homeostasis. Conversely, Th17 cells and their effector molecules interleukin 17A (IL-17A), IL-17F, interferon (IFN)γ, tumor necrosis factor (TNF)α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are implicated in the pathology of rheumatoid arthritis (RA). Interactions between Th17 cells and other immune cells or stromal cells that are present in the synovial tissue during the earliest phases of the disease, may eventually lead to chronic inflammation, irreversible cartilage degradation and bone erosions...
December 15, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29242008/immune-responses-to-peptides-containing-homocitrulline-or-citrulline-in-the-dr4-transgenic-mouse-model-of-rheumatoid-arthritis
#13
Patrick Lac, Sheri Saunders, Elena Tutunea-Fatan, Lillian Barra, David A Bell, Ewa Cairns
Antibodies to proteins/peptides containing citrulline are hallmarks of Rheumatoid Arthritis (RA). These antibodies are strongly associated with the expression of the Shared Epitope (SE). RA patients also generate antibodies to homocitrulline-containing proteins/peptides (also referred to as anti-carbamylated protein antibodies (Anti-CarP)). This study was undertaken to investigate the relationship between homocitrulline and citrulline immune responses using an established mouse model of RA: DR4-transgenic (DR4tg) mice that express the human SE...
December 11, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29233566/activation-of-thyroid-antigen-reactive-b-cells-in-recent-onset-autoimmune-thyroid-disease-patients
#14
Mia J Smith, Marynette Rihanek, Brianne M Coleman, Peter A Gottlieb, Virginia D Sarapura, John C Cambier
Autoimmune thyroid disease (AITD), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is the most common autoimmune disorder in the United States, affecting over 20 million people. At the time of diagnosis, both HD and GD are characterized by the accumulation of B and T lymphocytes in the thyroid gland and production of autoantibodies targeting the thyroid, indicating that a breach in tolerance of autoreactive lymphocytes has occurred. However, few studies have sought to understand the underlying pathogenesis of AITD that ultimately leads to production of autoantibodies and loss of thyroid function...
December 9, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29224923/allele-specific-methylation-of-type-1-diabetes-susceptibility-genes
#15
Alida S D Kindt, Rainer W Fuerst, Jan Knoop, Michael Laimighofer, Tanja Telieps, Markus Hippich, Maria A Woerheide, Simone Wahl, Rory Wilson, Eva-Maria Sedlmeier, Angela Hommel, John A Todd, Jan Krumsiek, Anette-G Ziegler, Ezio Bonifacio
The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype...
December 7, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29203226/innately-versatile-%C3%AE-%C3%AE-17%C3%A2-t-cells-in-inflammatory-and-autoimmune-diseases
#16
REVIEW
Pedro H Papotto, Annika Reinhardt, Immo Prinz, Bruno Silva-Santos
IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through an intricate process involving both T cell receptor-dependent and -independent signals, which allows them to readily produce IL-17 upon stimulation...
December 1, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29191573/excessive-interferon-%C3%AE-signaling-in-autoimmunity-alters-glycosphingolipid-processing-in-b-cells
#17
Andy Hee-Meng Tan, Arleen Sanny, Sze-Wai Ng, Ying-Swan Ho, Nurhidayah Basri, Alison Ping Lee, Kong-Peng Lam
Excessive interferon-α (IFN-α) production by innate immune cells is a hallmark of autoimmune diseases. What other cell type secretes IFN-α and how IFN-α affects immune cell metabolism and homeostasis in autoimmunity are largely unclear. Here, we report that autoimmune B cells, arising from two different B cell-specific genetic lesions in mice, secrete IFN-α. In addition, IFN-α, found in abundance in autoimmunity, elicited profound changes in the B cell lipidome, increasing their expression of glycosphingolipids (GSLs) and leading to their CD1d-mediated depletion of iNKT cells in vitro and in vivo...
November 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29191572/th17%C3%A2-cells-in-primary-sj%C3%A3-gren-s-syndrome-pathogenicity-and-plasticity
#18
REVIEW
Gwenny M Verstappen, Odilia B J Corneth, Hendrika Bootsma, Frans G M Kroese
Th17 cells play an important physiological role at mucosal barriers, and are involved in inflammatory responses to pathogens. Th17 cells and their signature cytokine IL-17 are also present in salivary gland lesions of primary Sjögren's syndrome (pSS) patients and can be elevated in their peripheral blood. In pSS patients, clear correlations between increased Th17 cell activity and symptoms of the disease have not been found, but Th17 cells may contribute to disease progression, for example by supporting autoreactive B cell responses...
November 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29183643/selective-targeting-of-pro-inflammatory-th1-cells-by-microrna-148a-specific-antagomirs-in%C3%A2-vivo
#19
Patrick Maschmeyer, Georg Petkau, Francesco Siracusa, Jakob Zimmermann, Franziska Zügel, Anja Andrea Kühl, Katrin Lehmann, Sarah Schimmelpfennig, Melanie Weber, Claudia Haftmann, René Riedel, Markus Bardua, Gitta Anne Heinz, Cam Loan Tran, Bimba Franziska Hoyer, Falk Hiepe, Sebastian Herzog, Jürgen Wittmann, Nikolaus Rajewsky, Fritz Georg Melchers, Hyun-Dong Chang, Andreas Radbruch, Mir-Farzin Mashreghi
In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic protein Bim and promotes their survival. Here we use sequence-specific cholesterol-modified oligonucleotides against miR-148a (antagomir-148a) for the selective elimination of pro-inflammatory Th1 cells in vivo. In the murine model of transfer colitis, antagomir-148a treatment reduced the number of pro-inflammatory Th1 cells in the colon of colitic mice by 50% and inhibited miR-148a expression by 71% in the remaining Th1 cells...
November 25, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29183642/tick-borne-diseases-and-autoimmunity-a-comprehensive-review
#20
REVIEW
Yhojan Rodríguez, Manuel Rojas, M Eric Gershwin, Juan-Manuel Anaya
Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation...
November 25, 2017: Journal of Autoimmunity
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