Systemic lupus erythematosus: Diagnosis and clinical management.
Abstract Systemic lupus erythematosus (SLE) is a worldwide chronic autoimmune disease which may affect every organ and tissue. Genetic predisposition, environmental triggers, and the hormonal milieu, interplay in disease development and activity. Clinical manifestations and the pattern of organ involvement are widely heterogenous, reflecting the complex mosaic of disrupted molecular pathways converging into the SLE clinical phenotype. The SLE complex pathogenesis involves multiple cellular components of the innate and immune systems, presence of autoantibodies and immunocomplexes, engagement of the complement syst...
Source: Journal of Autoimmunity - November 15, 2018 Category: Allergy & Immunology Authors: Fava A, Petri M Tags: J Autoimmun Source Type: research

A long-lived IL-2 mutein that selectively activates and expands regulatory T cells as a therapy for autoimmune disease.
Abstract Susceptibility to multiple autoimmune diseases is associated with common gene polymorphisms influencing IL-2 signaling and Treg function, making Treg-specific expansion by IL-2 a compelling therapeutic approach to treatment. As an in vivo IL-2 half-life enhancer we used a non-targeted, effector-function-silent human IgG1 as a fusion protein. An IL-2 mutein (N88D) with reduced binding to the intermediate affinity IL-2Rβγ receptor was engineered with a stoichiometry of two IL-2N88D molecules per IgG, i.e. IgG-(IL-2N88D)2. The reduced affinity of IgG-(IL-2N88D)2 for the IL-2Rβγ receptor...
Source: Journal of Autoimmunity - November 13, 2018 Category: Allergy & Immunology Authors: Peterson LB, Bell CJM, Howlett SK, Pekalski ML, Brady K, Hinton H, Sauter D, Todd JA, Umana P, Ast O, Waldhauer I, Freimoser-Grundschober A, Moessner E, Klein C, Hosse RJ, Wicker LS Tags: J Autoimmun Source Type: research

Changes in the composition of the upper respiratory tract microbial community in granulomatosis with polyangiitis.
n M Abstract Dysbiosis¸ i.e. changes in microbial composition at a mucosal interface, is implicated in the pathogenesis of many chronic inflammatory and autoimmune diseases. To assess the composition of the microbial upper respiratory tract (URT) community in patients with granulomatosis with polyangiitis (GPA), we used culture-independent high-throughput methods. In this prospective clinical study, nasal swabs were collected from patients with GPA, patients with rheumatoid arthritis (RA, disease control), and healthy controls. Nasal bacterial taxa were assessed using V3-V4 region 16S rRNA amplicon sequencin...
Source: Journal of Autoimmunity - November 9, 2018 Category: Allergy & Immunology Authors: Lamprecht P, Fischer N, Huang J, Burkhardt L, Lütgehetmann M, Arndt F, Rolfs I, Kerstein A, Iking-Konert C, Laudien M Tags: J Autoimmun Source Type: research

Prognostic models in primary biliary cholangitis.
Abstract Risk prediction modelling is important to better understand the determinants of the course and outcome of PBC and to inform the risk across the disease continuum in PBC enabling risk-stratified follow-up care and personalised therapy. Current prognostic models in PBC are based on treatment response to ursodeoxycholic acid because of the well-established relationship between alkaline phosphatase on treatment and long-term outcome. In addition, serum alkaline phosphatase correlates with ductular reaction and biliary metaplasia, which are hallmark of biliary injury. Considering the waiting time for treatment...
Source: Journal of Autoimmunity - November 9, 2018 Category: Allergy & Immunology Authors: Cristoferi L, Nardi A, Ronca V, Invernizzi P, Mells G, Carbone M Tags: J Autoimmun Source Type: research

Shared gut, but distinct oral microbiota composition in primary Sj ögren's syndrome and systemic lupus erythematosus.
CONCLUSIONS: pSS and SLE patients share similar alterations in gut microbiota composition, distinguishing patients from individuals in the general population, while oral microbiota composition shows disease-specific differences between pSS and SLE patients. PMID: 30416033 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 9, 2018 Category: Allergy & Immunology Authors: van der Meulen TA, Harmsen HJM, Vila AV, Kurilshikov A, Liefers SC, Zhernakova A, Fu J, Wijmenga C, Weersma RK, de Leeuw K, Bootsma H, Spijkervet FKL, Vissink A, Kroese FGM Tags: J Autoimmun Source Type: research

Novel mechanism for estrogen receptor alpha modulation of murine lupus.
Abstract Female sex is a risk factor for lupus. Sex hormones, sex chromosomes and hormone receptors are implicated in the pathogenic pathways in lupus. Estrogen receptor alpha (ERα) knockout (KO) mice are used for defining hormone receptor effects in lupus. Prior studies of ERα KO in lupus have conflicting results, likely due to sex hormone levels, different lupus strains and different ERα KO constructs. Our objective was to compare a complete KO of ERα vs. the original functional KO of ERα (expressing a short ERα) on disease expression and immune phenotype, while controlling se...
Source: Journal of Autoimmunity - November 8, 2018 Category: Allergy & Immunology Authors: Cunningham MA, Richard ML, Wirth JR, Scott JL, Eudaly J, Ruiz P, Gilkeson GS Tags: J Autoimmun Source Type: research

Novel therapeutic targets in autoimmune hepatitis.
This article highlights new therapeutic approaches based on our growing knowledge on the pathophysiology of AIH. It focuses on cell-based therapies that strengthen or restore immune tolerance. An additional focus lies on new therapeutic agents showing promising results in non-hepatic autoimmune diseases that have a potential for treating AIH. The dynamics in the whole field of innovative therapies for non-hepatic autoimmune diseases will hopefully improve the therapeutic armamentarium for AIH patients in the future. PMID: 30401504 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 3, 2018 Category: Allergy & Immunology Authors: Taubert R, Hupa-Breier KL, Jaeckel E, Manns MP Tags: J Autoimmun Source Type: research

PD-1 immunobiology in systemic lupus erythematosus.
Abstract Programmed death (PD)-1 receptors and their ligands have been identified in the pathogenesis and development of systemic lupus erythematosus (SLE). Two key pathways, toll-like receptor and type I interferon, are significant to SLE pathogenesis and modulate the expression of PD-1 and the ligands (PD-L1, PD-L2) through activation of NF-κB and/or STAT1. These cell signals are regulated by tyrosine kinase (Tyro, Axl, Mer) receptors (TAMs) that are aberrantly activated in SLE. STAT1 and NF-κB also exhibit crosstalk with the aryl hydrocarbon receptor (AHR). Ligands to AHR are identified in SLE etiol...
Source: Journal of Autoimmunity - November 2, 2018 Category: Allergy & Immunology Authors: Curran CS, Gupta S, Sanz I, Sharon E Tags: J Autoimmun Source Type: research

De novo autoimmune hepatitis -is this different in adults compared to children?
Abstract De novo autoimmune hepatitis (AIH) is an unusual cause of graft dysfunction after liver transplantation. This entity was originally described in 1996 in children transplanted for conditions other than AIH, who developed biochemical and histological features similar to AIH and responded to the therapy of classical AIH with steroids and azathioprine. In the last two decades, there have been reports of occurrence of de novo AIH in pediatric and adult liver transplant recipients, in the latter often being given different nomenclature including 'plasma cell hepatitis'. Typical causes of graft dysfunction in li...
Source: Journal of Autoimmunity - November 2, 2018 Category: Allergy & Immunology Authors: Kerkar N, Vergani D Tags: J Autoimmun Source Type: research

Autoimmune liver disease serology in acute hepatitis E virus infection.
In conclusion, autoantibodies are frequently present during acute HEV infection, indicating that HEV should always be excluded before diagnosing AIH. Importantly, a minority of patients with acute hepatitis E develops AIH-specific autoantibodies, and, though they did not progress to autoimmune liver disease in the short-term, they warrant long-term monitoring. PMID: 30336842 [PubMed - in process] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 20, 2018 Category: Allergy & Immunology Authors: Terziroli Beretta-Piccoli B, Ripellino P, Gobbi C, Cerny A, Baserga A, Di Bartolomeo C, Bihl F, Deleonardi G, Melidona L, Grondona AG, Mieli-Vergani G, Vergani D, Muratori L, Swiss Autoimmune Hepatitis Cohort Study Group Tags: J Autoimmun Source Type: research

Structural mapping of hot spots within human CASPR2 discoidin domain for autoantibody recognition.
Abstract Accumulating evidence has showed that anti-CASPR2 autoantibodies occur in a long list of neurological immune disorders including limbic encephalitis (LE). Belonging to the well-known neurexin superfamily, CASPR2 has been suggested to be a central node in the molecular networks controlling neurodevelopment. Distinct from other subfamilies in the neurexin superfamily, the CASPR subfamily features a unique discoidin (Disc) domain. As revealed by our and others' recent studies, CASPR2 Disc domain bears a major epitope for autoantibodies. However, structural information on CASPR2 recognition by autoantibodies ...
Source: Journal of Autoimmunity - October 15, 2018 Category: Allergy & Immunology Authors: Liang W, Zhang J, Saint-Martin M, Xu F, Noraz N, Liu J, Honnorat J, Liu H Tags: J Autoimmun Source Type: research

White blood cell mitochondrial DNA copy number is decreased in rheumatoid arthritis and linked with risk factors. A twin study.
Abstract Low mitochondrial DNA copy number (mtDNA CN) has been associated with e.g. cancer, cardiovascular and autoimmune diseases. We aimed to study a potential association between mtDNA CN and rheumatoid arthritis (RA). The relative quantity of mitochondrial DNA compared to nuclear DNA was measured in peripheral white blood cells from 149 RA affected twin pairs and 1321 non-affected twin pairs. Multiple regression analysis including RA discordant twin pairs was performed in order to separate specific effects of RA and familial RA predisposition using non-RA affected twin pairs as reference group. In addition, we...
Source: Journal of Autoimmunity - October 13, 2018 Category: Allergy & Immunology Authors: Svendsen AJ, Tan Q, Jakobsen MA, Thyagarajan B, Nygaard M, Christiansen L, Mengel-From J Tags: J Autoimmun Source Type: research

Arginine methylation of FOXP3 is crucial for the suppressive function of regulatory T cells.
Abstract Forkhead box transcription factor 3 (FOXP3) plays a pivotal role in the suppressive function of regulatory T cells. In addition to mRNA levels, FOXP3 activity can also be controlled by posttranslational mechanisms, which have not been studied in a comprehensive manner. Through extensive screening using selective inhibitors, we demonstrate that the inhibition of type I protein arginine methytransferases (PRMTs) attenuates the suppressive functions of regulatory T cells. FOXP3 undergoes methylation on arginine residues at positions 48 and 51 by interacting with protein arginine methyltransferase 1 (PRMT1). ...
Source: Journal of Autoimmunity - October 11, 2018 Category: Allergy & Immunology Authors: Kagoya Y, Saijo H, Matsunaga Y, Guo T, Saso K, Anczurowski M, Wang CH, Sugata K, Murata K, Butler MO, Arrowsmith CH, Hirano N Tags: J Autoimmun Source Type: research

A stochastic epigenetic Mendelian oligogenic disease model for type 1 diabetes.
Abstract The incidence of type 1 diabetes (T1D) and some other complex diseases is increasing. The cause has been attributed to an undefined changing environment. We examine the role of the environment (or any changing non-genetic mechanism) in causing the rising incidence, and find much evidence against it: 1) Dizygotic twin T1D concordance is the same as siblings of patients in general; 2) If the environment is responsible for both the discordance among identical twins of patients with T1D and its rising incidence, the twin concordance rate should be rising, but it is not; 3) Migrants from high-to low-incidence ...
Source: Journal of Autoimmunity - October 8, 2018 Category: Allergy & Immunology Authors: Alper CA, Larsen CE, Trautwein MR, Alford DR Tags: J Autoimmun Source Type: research

Epigenome-wide association study of peripheral blood mononuclear cells in systemic lupus erythematosus: Identifying DNA methylation signatures associated with interferon-related genes based on ethnicity and SLEDAI.
Abstract Systemic lupus erythematosus (SLE or lupus) is a heterogeneous autoimmune disease characterized by the involvement of multiple organs and the production of antinuclear antibodies. DNA methylation plays an important role in the pathogenesis of lupus. We have performed an epigenome-wide DNA methylation study in lupus and healthy control (non-lupus) subjects to identify epigenetic patterns in lupus characterized ethnicity and SLE disease activity index (SLEDAI). A total of fifty-seven lupus patients (39 African American (AA) and 18 European American (EA)) and 33 healthy controls (17 AA and 16 EA) were stud...
Source: Journal of Autoimmunity - October 6, 2018 Category: Allergy & Immunology Authors: Joseph S, George NI, Green-Knox B, Treadwell EL, Word B, Yim S, Lyn-Cook B Tags: J Autoimmun Source Type: research

ARID3a gene profiles are strongly associated with human interferon alpha production.
Abstract Type I interferons (IFN) causes inflammatory responses to pathogens, and can be elevated in autoimmune diseases such as systemic lupus erythematosus (SLE). We previously reported unexpected associations of increased numbers of B lymphocytes expressing the DNA-binding protein ARID3a with both IFN alpha (IFNα) expression and increased disease activity in SLE. Here, we determined that IFNα producing low density neutrophils (LDNs) and plasmacytoid dendritic cells (pDCs) from SLE patients exhibit strong associations between ARID3a protein expression and IFNα production. Moreover, SLE disease ...
Source: Journal of Autoimmunity - October 5, 2018 Category: Allergy & Immunology Authors: Ratliff ML, Garton J, Garman L, Barron MD, Georgescu C, White KA, Chakravarty E, Wren JD, Montgomery CG, James JA, Webb CF Tags: J Autoimmun Source Type: research

Endogenous IL-10 maintains immune tolerance but IL-10 gene transfer exacerbates autoimmune cholangitis.
In conclusion, our data demonstrate that endogenous IL-10 is critical in the maintenance of immune tolerance but exogenous administration of IL-10 exacerbates liver inflammation and fibrosis. Furthermore, the distinctive presence of inflammatory immune cell populations and collagen expression in AAV-IL-10 treated naïve mice cautions against the clinical use of exogenous IL-10 in patients with autoimmune cholangitis. PMID: 30274824 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 28, 2018 Category: Allergy & Immunology Authors: Hsueh YH, Chen HW, Syu BJ, Lin CI, Leung PSC, Gershwin ME, Chuang YH Tags: J Autoimmun Source Type: research

CRL4DCAF2 is required for mature T-cell expansion via Aurora B-regulated proteasome activity.
Abstract The proliferation of T cells in peripheral lymphoid tissues requires T cell receptor (TCR)-mediated cell cycle entry. However, the underlying mechanism regulating cell cycle progression in mature T cells is incompletely understood. Here, we have identified an E3 ubiquitin ligase, CRL4DCAF2, as a critical mediator controlling M phase exit in activated T cells. DCAF2 expression is induced upon TCR stimulation and its deficiency attenuates T cell expansion. Additionally, DCAF2 T cell-specific knockout mice display impaired peripheral T cell maintenance and reduced severity of various autoimmune diseases. Con...
Source: Journal of Autoimmunity - September 20, 2018 Category: Allergy & Immunology Authors: Fan K, Wang F, Li Y, Chen L, Gao Z, Zhang Y, Duan JY, Huang T, Zhong J, Liu RB, Mao X, Fan H, Guo X, Jin J Tags: J Autoimmun Source Type: research

GPR15+ T cells are Th17 like, increased in smokers and associated with multiple sclerosis.
In conclusion, we have identified a proinflammatory cell type linking smoking with pathogenic immune cell functions in RRMS. PMID: 30245027 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 20, 2018 Category: Allergy & Immunology Authors: Ammitzbøll C, von Essen MR, Börnsen L, Petersen ER, McWilliam O, Ratzer R, Jeppe RC, Oturai AB, Søndergaard HB, Sellebjerg F Tags: J Autoimmun Source Type: research

T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation.
Abstract The follicular helper T cell (TFH) are established regulators of germinal center (GC) B cells, whether TFH have pathogenic potential independent of B cells is unknown. Based on in vitro TFH cell differentiation, in vivo T cell transfer animal colitis model, and intestinal tissues of inflammatory bowel disease (IBD) patients, TFH and its functions in colitis development were analyzed by FACS, ChIP, ChIP-sequencing, WB, ELISA and PCR. Herein we demonstrate that intestinal tissues of patients and colon tissues obtained from Rag1-/- recipients of naïve CD4+ T cells with colitis, each over-express TFH-ass...
Source: Journal of Autoimmunity - September 18, 2018 Category: Allergy & Immunology Authors: Zhang R, Qi CF, Hu Y, Shan Y, Hsieh YP, Xu F, Lu G, Dai J, Gupta M, Cui M, Peng L, Yang J, Xue Q, Chen-Liang R, Chen K, Zhang Y, Fung-Leung WP, Mora JR, Li L, Morse HC, Ozato K, Heeger PS, Xiong H Tags: J Autoimmun Source Type: research

Increased ischemic stroke, acute coronary artery disease and mortality in patients with granulomatosis with polyangiitis and microscopic polyangiitis.
CONCLUSION: AAV have a significantly increased risk of mortality, ischemic stroke, and coronary artery disease. PMID: 30236485 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 17, 2018 Category: Allergy & Immunology Authors: Mourguet M, Chauveau D, Faguer S, Ruidavets JB, Béjot Y, Ribes D, Huart A, Alric L, Balardy L, Astudillo L, Adoue D, Sailler L, Pugnet G Tags: J Autoimmun Source Type: research

IL-17A is functionally relevant and a potential therapeutic target in bullous pemphigoid.
hmidt E Abstract IL-17A has been identified as key regulatory molecule in several autoimmune and chronic inflammatory diseases followed by the successful use of anti-IL-17 therapy, e.g. in ankylosing spondylitis and psoriasis. Bullous pemphigoid (BP) is the most frequent autoimmune blistering disease with a high need for more specific, effective and safe treatment options. The aim of this study was to clarify the pathophysiological importance of IL-17A in BP. We found elevated numbers of IL-17A+ CD4+ lymphocytes in the peripheral blood of BP patients and identified CD3+ cells as major source of IL-17A in early BP ...
Source: Journal of Autoimmunity - September 12, 2018 Category: Allergy & Immunology Authors: Chakievska L, Holtsche MM, Künstner A, Goletz S, Petersen BS, Thaci D, Ibrahim SM, Ludwig RJ, Franke A, Sadik CD, Zillikens D, Hölscher C, Busch H, Schmidt E Tags: J Autoimmun Source Type: research

Autophagy: A new concept in autoimmunity regulation and a novel therapeutic option.
Abstract Nowadays, pharmacologic treatments of autoinflammatory diseases are largely palliative rather than curative. Most of them result in non-specific immunosuppression, which can be associated with broad disruption of natural and induced immunity with significant and sometimes serious unwanted injuries. Among the novel strategies that are under development, tools that modulate the immune system to restore normal tolerance mechanisms are central. In these approaches, peptide therapeutics constitute a class of agents that display many physicochemical advantages. Within this class of potent drugs, the phosphopept...
Source: Journal of Autoimmunity - September 12, 2018 Category: Allergy & Immunology Authors: Bonam SR, Wang F, Muller S Tags: J Autoimmun Source Type: research

Efficacy of the anti-IL 17 secukinumab in refractory Beh çet's syndrome: A preliminary study.
Efficacy of the anti-IL 17 secukinumab in refractory Behçet's syndrome: A preliminary study. J Autoimmun. 2018 Sep 11;: Authors: Di Scala G, Bettiol A, Cojan RD, Finocchi M, Silvestri E, Emmi G Abstract OBJECTIVE: To evaluate the efficacy and safety of secukinumab in Behçet's patients with active mucocutaneous and articular manifestations refractory to previous treatments. METHODS: We retrospectively evaluated 5 patients treated with the IL17-inhibitor secukinumab and diagnosed with Behçet according to ISG/ICBD criteria. All patients had active mucocutaneous and articular man...
Source: Journal of Autoimmunity - September 11, 2018 Category: Allergy & Immunology Authors: Di Scala G, Bettiol A, Cojan RD, Finocchi M, Silvestri E, Emmi G Tags: J Autoimmun Source Type: research

MicroRNA-183 and microRNA-96 are associated with autoimmune responses by regulating T cell activation.
n W Abstract MircoRNAs (miRs) are small molecules that regulate gene expression at the posttranscriptional level. They have been proposed to be involved in the regulation of several immune responses including autoimmunity. Here, we identified miR-183 and miR-96 to be highly expressed in CD4+ T cells from peripheral blood of Graves' orbitopathy (GO) patients as well as in human and murine T cells upon activation in vitro. By using Luciferase-based binding assays, we identified EGR-1 as target for miR-183 and miR-96. Overexpression of miR-183 and miR-96 in murine CD4+ T cells by retroviral gene transfer resulted in ...
Source: Journal of Autoimmunity - September 7, 2018 Category: Allergy & Immunology Authors: Thiel J, Alter C, Luppus S, Eckstein A, Tan S, Führer D, Pastille E, Westendorf AM, Buer J, Hansen W Tags: J Autoimmun Source Type: research

Altered expression of microRNA-23a in psoriatic arthritis modulates synovial fibroblast pro-inflammatory mechanisms via phosphodiesterase 4B.
CONCLUSIONS: In PsA, dysregulated miR-23a expression contributes to synovial inflammation through enhanced SFC activation, via PDE4B signalling, and identifies a novel anti-inflammatory mechanism of PDE4 blockade. PMID: 30181004 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 1, 2018 Category: Allergy & Immunology Authors: Wade SM, Trenkmann M, McGarry T, Canavan M, Marzaioli V, Wade SC, Veale DJ, Fearon U Tags: J Autoimmun Source Type: research

Commensal bacteria aggravate allergic asthma via NLRP3/IL-1 β signaling in post-weaning mice.
Commensal bacteria aggravate allergic asthma via NLRP3/IL-1β signaling in post-weaning mice. J Autoimmun. 2018 Sep;93:104-113 Authors: Huang C, Wang J, Zheng X, Chen Y, Zhou R, Wei H, Sun R, Tian Z Abstract Perturbation of commensal bacteria by antibiotic exposure aggravates ovalbumin (OVA)-induced allergic asthma in pre-weaning mice. However, the influence of dysbiosis of commensal bacteria on asthma development in post-weaning mice is still limited. Here, we treated 3-week-old post-weaning mice with antibiotics to disrupt commensal bacteria and then established OVA-induced allergic asthma by pe...
Source: Journal of Autoimmunity - August 29, 2018 Category: Allergy & Immunology Authors: Huang C, Wang J, Zheng X, Chen Y, Zhou R, Wei H, Sun R, Tian Z Tags: J Autoimmun Source Type: research

Catastrophic antiphospholipid syndrome: Lessons from 14 cases successfully treated in a single center. A narrative report.
Abstract The study aimed to evaluate the clinical significance of laboratory findings in patients with catastrophic antiphospholipid syndrome (CAPS) and to report the effects of a well-defined treatment protocol in 14 consecutive cases. Thirteen patients (12 presenting one and one presenting two episodes of CAPS) were consecutively treated and monitored between 1986 and 2017. Antiphospholipid antibody (aPL) characteristics of the patients were compared with those of 64 matched controls (45 antiphospholipid syndrome patients and 19 aPL carriers) who did not develop CAPS during the same mean follow-up period (12 yea...
Source: Journal of Autoimmunity - August 29, 2018 Category: Allergy & Immunology Authors: Ruffatti A, De Silvestro G, Marson P, Tonello M, Calligaro A, Favaro M, Del Ross T, Hoxha A, Mattia E, Pengo V Tags: J Autoimmun Source Type: research

Identification of loci where DNA methylation potentially mediates genetic risk of type 1 diabetes.
Abstract The risk of Type 1 Diabetes (T1D) comprises both genetic and environmental components. We investigated whether genetic susceptibility to T1D could be mediated by changes in DNA methylation, an epigenetic mechanism that potentially plays a role in autoimmune diabetes. From enrichment analysis, we found that there was a common genetic influence for both DNA methylation and T1D across the genome, implying that methylation could be either on the causal pathway to T1D or a non-causal biomarker of T1D genetic risk. Using data from a general population comprising blood samples taken at birth (n = 844), child...
Source: Journal of Autoimmunity - August 29, 2018 Category: Allergy & Immunology Authors: Ye J, Richardson TG, McArdle WL, Relton CL, Gillespie KM, Suderman M, Hemani G Tags: J Autoimmun Source Type: research

Evidence for a potential role of miR-1908-5p and miR-3614-5p in autoimmune disease risk using integrative bioinformatics.
Abstract Genome-wide association studies (GWAS) have identified a large number of genetic risk loci for autoimmune diseases. However, the functional variants underlying these disease associations remain largely unknown. There is evidence that microRNA-mediated regulation may play an important role in this context. Therefore, we assessed whether autoimmune disease loci unfold their effects via altering microRNA expression in relevant immune cells. To this end, we performed comprehensive data integration of many large and publicly available datasets to combine information on autoimmune disease risk loci with RNA-Seq...
Source: Journal of Autoimmunity - August 21, 2018 Category: Allergy & Immunology Authors: Wohlers I, Bertram L, Lill CM Tags: J Autoimmun Source Type: research

Overall survival and mortality risk factors in Takayasu's arteritis: A multicenter study of 318 patients.
CONCLUSION: The overall mortality in our Takayasu cohort was 5% after a median follow-up of 6.1 years. We identified specific characteristics that distinguish TA patients at highest risk for death and vascular complications. PMID: 30122419 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 16, 2018 Category: Allergy & Immunology Authors: Mirouse A, Biard L, Comarmond C, Lambert M, Mekinian A, Ferfar Y, Kahn JE, Benhamou Y, Chiche L, Koskas F, Cluzel P, Hachulla E, Messas E, Cacoub P, Mirault T, Resche-Rigon M, Saadoun D, French Takayasu network Tags: J Autoimmun Source Type: research

Chimeric antigen receptor (CAR) T cells targeting a pathogenic MHC class II:peptide complex modulate the progression of autoimmune diabetes.
Abstract A primary initiating epitope in the NOD mouse model of Type 1 Diabetes (T1D) lies between residues 9 and 23 of the insulin B chain. The B:9-23 peptide can bind to the NOD MHC class II molecule (I-Ag7) in multiple registers, but only one, (register 3, R3), creates complexes able to stimulate the majority of pathogenic B:9-23-specific CD4+ T cells. Previously we generated a monoclonal antibody (mAb287) that targets this critical I-Ag7-B:9-23(R3) complex. When given weekly to pre-diabetic mice at either early or late stages of disease, mAb287 was able to delay or prevent T1D in the treated animals. Although ...
Source: Journal of Autoimmunity - August 16, 2018 Category: Allergy & Immunology Authors: Zhang L, Sosinowski T, Aaron R, Cepeda JR, Sekhar NS, Hartig SM, Miao D, Yu L, Pietropaolo M, Davidson HW Tags: J Autoimmun Source Type: research

Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo.
Abstract Fingolimod is an approved therapeutic option for patients with relapsing-remitting multiple sclerosis that primarily functions by sequestering T cells in lymph nodes inhibiting their egress to the central nervous system. However, recent data suggests that Fingolimod may also directly affect the immune cell function. Here we examined the in vivo effects of Fingolimod in modulating the phenotype and function of T cell and Foxp3 regulatory T cell populations in patients with multiple sclerosis under Fingolimod treatment. Besides decreasing the cell numbers in peripheral blood and sera levels of pro-inflammat...
Source: Journal of Autoimmunity - August 16, 2018 Category: Allergy & Immunology Authors: Dominguez-Villar M, Raddassi K, Danielsen AC, Guarnaccia J, Hafler DA Tags: J Autoimmun Source Type: research

Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN- γ secreting cells.
Increased sensitivity of Treg cells from patients with PBC to low dose IL-12 drives their differentiation into IFN-γ secreting cells. J Autoimmun. 2018 Aug 14;: Authors: Liaskou E, Patel SR, Webb G, Bagkou Dimakou D, Akiror S, Krishna M, Mells G, Jones DE, Bowman SJ, Barone F, Fisher BA, Hirschfield GM Abstract IL-12 is a pro-inflammatory cytokine that induces the production of interferon-γ (IFNγ) and favours the differentiation of T helper 1 (Th1) cells. In the presence of IL-12 human Treg cells acquire a Th1-like phenotype with reduced suppressive activity in vitro. Primary biliary...
Source: Journal of Autoimmunity - August 14, 2018 Category: Allergy & Immunology Authors: Liaskou E, Patel SR, Webb G, Bagkou Dimakou D, Akiror S, Krishna M, Mells G, Jones DE, Bowman SJ, Barone F, Fisher BA, Hirschfield GM Tags: J Autoimmun Source Type: research

Interferon alpha: The key trigger of type 1 diabetes.
Abstract IFNα is a cytokine essential to a vast array of immunologic processes. Its induction early in the innate immune response provides a priming mechanism that orchestrates numerous subsequent pathways in innate and adaptive immunity. Despite its beneficial effects in viral infections IFNα has been reported to be associated with several autoimmune diseases including autoimmune thyroid disease, systemic lupus erythematosus, rheumatoid arthritis, primary biliary cholangitis, and recently emerged as a major cytokine that triggers Type 1 Diabetes. In this review, we dissect the role of IFNα in T1...
Source: Journal of Autoimmunity - August 13, 2018 Category: Allergy & Immunology Authors: Lombardi A, Tsomos E, Hammerstad SS, Tomer Y Tags: J Autoimmun Source Type: research

Mutations of deubiquitinase OTUD1 are associated with autoimmune disorders.
Abstract Dysregulation of innate immunity accompanied by excessive interferon production contributes to autoimmune disease. However, the mechanism by which the immune response is modulated in autoimmune disorders is largely unknown. Here we identified loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases. Under inflammatory conditions, inducible OTUD1 acts as an immune checkpoint and blocks RIG-I-like receptors signaling. As a deubiquitinase, OTUD1 directly interacts with transcription factor IRF3 and removes the K63-linked poly-ubiquitin chains on IRF3 Lysine 98, which inhibits IRF3 nuc...
Source: Journal of Autoimmunity - August 9, 2018 Category: Allergy & Immunology Authors: Lu D, Song J, Sun Y, Qi F, Liu L, Jin Y, McNutt MA, Yin Y Tags: J Autoimmun Source Type: research

HIF-1 α-induced xenobiotic transporters promote Th17 responses in Crohn's disease.
We report here that in vitro exposure of Th17-cells from Crohn's disease patients to hypoxia limits responsiveness to AhR stimulation by UCB, as reflected by lower CD39 levels. Blockade of hypoxia-inducible-factor-1alpha (HIF-1α) upregulates CD39 and favors Th17-cell regulatory responses. Resistance of Th17-cells to AhR signaling results, in part, from HIF-1α-dependent induction of ATP-binding cassette (ABC) transporters: multidrug-resistance-protein-1 (MDR1) and multidrug-resistance-associated-protein-4 (MRP4). Increased ABC transporters promote efflux of suppressive AhR ligands, such as UCB, from Th17-cells. ...
Source: Journal of Autoimmunity - August 8, 2018 Category: Allergy & Immunology Authors: Xie A, Robles RJ, Mukherjee S, Zhang H, Feldbrügge L, Csizmadia E, Wu Y, Enjyoji K, Moss AC, Otterbein LE, Quintana FJ, Robson SC, Longhi MS Tags: J Autoimmun Source Type: research

A comprehensive review on adult onset Still's disease.
Abstract Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder of unknown etiology usually affecting young adults; spiking fever, arthritis and evanescent rash are commonly observed during the disease. Other frequently observed clinical features include sore throat, hepatomegaly, splenomegaly, lymphadenopathy and serositis. Furthermore, AOSD patients may experience different life-threating complications. Macrophage activation syndrome (MAS) has been reported up to 15% of AOSD patients and it is considered to be the most severe complication of the disease being characterised by high mortality rate....
Source: Journal of Autoimmunity - August 1, 2018 Category: Allergy & Immunology Authors: Giacomelli R, Ruscitti P, Shoenfeld Y Tags: J Autoimmun Source Type: research

Molecular mechanisms of autophagic memory in pathogenic T cells in human arthritis.
Abstract T-cell resilience is critical to the immune pathogenesis of human autoimmune arthritis. Autophagy is essential for memory T cell generation and associated with pathogenesis in rheumatoid arthritis (RA). Our aim here was to delineate the role and molecular mechanism of autophagy in resilience and persistence of pathogenic T cells from autoimmune arthritis. We demonstrated "Autophagic memory" as elevated autophagy levels in CD4+ memory T cells compared to CD4+ naive T cells and in Jurkat Human T cell line trained with starvation stress. We then showed increased levels of autophagy in pathogenic CD...
Source: Journal of Autoimmunity - August 1, 2018 Category: Allergy & Immunology Authors: Kumar P, Yao LJ, Saidin S, Paleja B, van Loosdregt J, Chua C, Arkachaisri T, Consolaro A, Gattorno M, Martini A, Pischel KD, Williams GW, Lotz M, Albani S Tags: J Autoimmun Source Type: research

Contribution of ancient human remains analysis to the understanding of the variability in HLA-B gene variants in relation to the diagnosis of spondyloarthropathies.
e;a C Abstract Genetic investigations on ancient human remains affected by rheumatological pathologies are a research field of particular interest for identifying the pathogenesis of diseases, especially those having an autoimmune background such as spondyloarthopaties (SpA). Reliable studies concerning this topic require collaboration between multiple disciplines, usually starting from paleopathologic observations up to molecular genetic screening. Here, we focused our investigation in a medieval necropolis in the Basque Country (13th-15th century, N = 163), which presents a high frequency of joint pathologie...
Source: Journal of Autoimmunity - July 28, 2018 Category: Allergy & Immunology Authors: Laza IM, Ventades NG, Hervella M, de-la-Rúa C Tags: J Autoimmun Source Type: research

NF- κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling.
NF-κB inducing kinase (NIK) is an essential post-transcriptional regulator of T-cell activation affecting F-actin dynamics and TCR signaling. J Autoimmun. 2018 Jul 27;: Authors: Lacher SM, Thurm C, Distler U, Mohebiany AN, Israel N, Kitic M, Ebering A, Tang Y, Klein M, Wabnitz GH, W.e F, Samstag Y, Bopp T, Kurschus FC, Simeoni L, Tenzer S, Waisman A Abstract NF-κB inducing kinase (NIK) is the key protein of the non-canonical NF-κB pathway and is important for the development of lymph nodes and other secondary immune organs. We elucidated the specific role of NIK in T cells using T-ce...
Source: Journal of Autoimmunity - July 27, 2018 Category: Allergy & Immunology Authors: Lacher SM, Thurm C, Distler U, Mohebiany AN, Israel N, Kitic M, Ebering A, Tang Y, Klein M, Wabnitz GH, Wanke F, Samstag Y, Bopp T, Kurschus FC, Simeoni L, Tenzer S, Waisman A Tags: J Autoimmun Source Type: research

mTOR pathway activation in large vessel vasculitis.
CONCLUSIONS: We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV. PMID: 30061014 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 27, 2018 Category: Allergy & Immunology Authors: Maciejewski-Duval A, Comarmond C, Leroyer A, Zaidan M, Le Joncour A, Desbois AC, Fouret JP, Koskas F, Cluzel P, Garrido M, Cacoub P, Saadoun D Tags: J Autoimmun Source Type: research

Foxa1 and Foxa2 in thymic epithelial cells (TEC) regulate medullary TEC and regulatory T-cell maturation.
Crompton T Abstract The Foxa1 and Foxa2 transcription factors are essential for mouse development. Here we show that they are expressed in thymic epithelial cells (TEC) where they regulate TEC development and function, with important consequences for T-cell development. TEC are essential for T-cell differentiation, lineage decisions and repertoire selection. Conditional deletion of Foxa1 and Foxa2 from murine TEC led to a smaller thymus with a greater proportion of TEC and a greater ratio of medullary to cortical TEC. Cell-surface MHCI expression was increased on cortical TEC in the conditional Foxa1Foxa2 knockou...
Source: Journal of Autoimmunity - July 27, 2018 Category: Allergy & Immunology Authors: Lau CI, Yánez DC, Solanki A, Papaioannou E, Saldaña JI, Crompton T Tags: J Autoimmun Source Type: research

Safety issues and recommendations for successful pregnancy outcome in systemic lupus erythematosus.
In conclusion, the use of specific guidelines on the management of SLE before and during pregnancy and lactation, and a better understanding of the use of immunosuppressive therapies have significantly increased pregnancy success. PMID: 30056945 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 27, 2018 Category: Allergy & Immunology Authors: Nahal SK, Selmi C, Gershwin ME Tags: J Autoimmun Source Type: research

In situ detection of PR3-ANCA+ B cells and alterations in the variable region of immunoglobulin genes support a role of inflamed tissue in the emergence of auto-reactivity in granulomatosis with polyangiitis.
r A Abstract Circulating anti-neutrophilic cytoplasmic autoantibodies targeting proteinase 3 (PR3-ANCA) are a diagnostic and pathogenic hallmark of granulomatosis with polyangiitis (GPA). It is, however, incompletely understood if inflamed tissue supports presence or emergence of PR3-ANCA+ B cells. In search of such cells in inflamed tissue of GPA, immunofluorescence staining for IgG and a common PR3-ANCA idiotype (5/7 Id) was undertaken. Few 5/7 Id+/IgG+ B cells were detected in respiratory and kidney tissue of GPA. To gain more insight into surrogate markers possibly indicative of an anti-PR3-response, a meta-an...
Source: Journal of Autoimmunity - July 24, 2018 Category: Allergy & Immunology Authors: Weppner G, Ohlei O, Hammers CM, Holl-Ulrich K, Voswinkel J, Bischof J, Hasselbacher K, Riemekasten G, Lamprecht P, Ibrahim S, Iking-Konert C, Recke A, Müller A Tags: J Autoimmun Source Type: research

Protein tyrosine phosphatase PTPN22 regulates LFA-1 dependent Th1 responses.
Abstract A missense C1858T single nucleotide polymorphism within PTPN22 is a strong genetic risk factor for the development of multiple autoimmune diseases. PTPN22 encodes a protein tyrosine phosphatase that negatively regulates immuno-receptor proximal Src and Syk family kinases. Notably, PTPN22 negatively regulates kinases downstream of T-cell receptor (TCR) and LFA-1, thereby setting thresholds for T-cell activation. Alterations to the quality of TCR and LFA-1 engagement at the immune synapse and the regulation of downstream signals can have profound effects on the type of effector T-cell response induced. Here...
Source: Journal of Autoimmunity - July 24, 2018 Category: Allergy & Immunology Authors: Sanchez-Blanco C, Clarke F, Cornish GH, Depoil D, Thompson SJ, Dai X, Rawlings DJ, Dustin ML, Zamoyska R, Cope AP, Purvis HA Tags: J Autoimmun Source Type: research

Molecular profiling of regulatory T cells in pulmonary sarcoidosis.
CONCLUSION: Our findings offer a deeper insight into the molecular mechanisms of Tregs reduced suppression and increased apoptosis in patients with PS. Based on the current results, future studies should focus on possible therapeutic effect of TLR-2 signaling inhibition. PMID: 30049532 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 23, 2018 Category: Allergy & Immunology Authors: Kachamakova-Trojanowska N, Jazwa-Kusior A, Szade K, Kasper L, Soja J, Andrychiewicz A, Jakiela B, Plutecka H, Sanak M, Jozkowicz A, Sladek K, Dulak J Tags: J Autoimmun Source Type: research

Gene expression profiling identifies distinct molecular signatures in thrombotic and obstetric antiphospholipid syndrome.
Abstract Antiphospholipid antibodies (aPL) cause vascular thrombosis (VT) and/or pregnancy morbidity (PM). Differential mechanisms however, underlying the pathogenesis of these different manifestations of antiphospholipid syndrome (APS) are not fully understood. Therefore, we compared the effects of aPL from patients with thrombotic or obstetric APS on monocytes to identify different molecular pathways involved in the pathogenesis of APS subtypes. VT or PM IgG induced similar numbers of differentially expressed (DE) genes in monocytes. However, gene ontology (GO) analysis of DE genes revealed disease-specific geno...
Source: Journal of Autoimmunity - July 19, 2018 Category: Allergy & Immunology Authors: Ripoll VM, Pregnolato F, Mazza S, Bodio C, Grossi C, McDonnell T, Pericleous C, Meroni PL, Isenberg DA, Rahman A, Giles IP Tags: J Autoimmun Source Type: research

Nrf2-mediated metabolic reprogramming of tolerogenic dendritic cells is protective against aplastic anemia.
Abstract Aplastic anemia (AA) is a rare disease characterized by immune-mediated suppression of bone marrow (BM) function resulting in progressive pancytopenia. Stem cell transplant and immunosuppressive therapies remain the major treatment choices for AA patients with limited benefit and undesired side effects. Here, we report for the first time the therapeutic utility of Nrf2-induced metabolically reprogrammed tolerogenic dendritic cells (TolDCs) in the suppression of AA in mice. CDDO-DFPA-induced Nrf2 activation resulted in a TolDC phenotype as evidenced by induction of IL-4, IL-10, and TGF-β and suppressi...
Source: Journal of Autoimmunity - July 16, 2018 Category: Allergy & Immunology Authors: Wei HJ, Gupta A, Kao WM, Almudallal O, Letterio JJ, Pareek TK Tags: J Autoimmun Source Type: research

Soluble antigen arrays disarm antigen-specific B cells to promote lasting immune tolerance in experimental autoimmune encephalomyelitis.
Abstract Autoreactive lymphocytes that escape central immune tolerance may be silenced via an endogenous peripheral tolerance mechanism known as anergy. Antigen-specific therapies capable of inducing anergy may restore patients with autoimmune diseases to a healthy phenotype while avoiding deleterious side effects associated with global immunosuppression. Inducing anergy in B cells may be a particularly potent intervention, as B cells can contribute to autoimmune diseases through multiple mechanisms and offer the potential for direct antigen-specific targeting through the B cell receptor (BCR). Our previous result...
Source: Journal of Autoimmunity - July 12, 2018 Category: Allergy & Immunology Authors: Hartwell BL, Pickens CJ, Leon M, Northrup L, Christopher MA, Griffin JD, Martinez-Becerra F, Berkland C Tags: J Autoimmun Source Type: research