Lessons from studying the AU-rich elements in chronic inflammation and autoimmunity.
Abstract AU-rich elements (AREs) comprise one of the most widely studied families of regulatory RNA structures met in RNAs engaged in complex immunological reactions. A multitude of genetic, molecular, holistic and functional studies have been utilized for the analyses of the AREs and their interactions to proteins that bind to them. Data stemming from these studies brought forth a world of RNA-related check-points against infection, chronic inflammation, tumor associated immunity, and autoimmunity; and the interest to capitalize the interactions of AREs for clinical management and therapy. They also provided less...
Source: Journal of Autoimmunity - October 8, 2019 Category: Allergy & Immunology Authors: Lourou N, Gavriilidis M, Kontoyiannis DL Tags: J Autoimmun Source Type: research

Complement C1q synergizes with PTX3 in promoting NLRP3 inflammasome over-activation and pyroptosis in rheumatoid arthritis.
In this study, we demonstrated that pentaxin 3 (PTX3), an essential component of innate immunity, was elevated in RA and preferentially bound to CD14+ monocytes. C1q promoted the binding and resulted in increased cell proliferation, activation and caspase-1-related late apoptotic cells (7-AAD+annexin V+), as well as enhanced release of inflammatory cytokines including TNF-α, IL-1β and IL-6. Serum from RA patients, compared with healthy controls, induced gasdermin D (GSDMD)-dependent pyroptosis in monocytes, and this ability was associated with disease activity. Moreover, PTX3 synergized with C1q to promote pyrop...
Source: Journal of Autoimmunity - October 7, 2019 Category: Allergy & Immunology Authors: Wu XY, Li KT, Yang HX, Yang B, Lu X, Zhao LD, Fei YY, Chen H, Wang L, Li J, Peng LY, Zheng WJ, Hou Y, Jiang Y, Shi Q, Zhang W, Zhang FC, Zhang JM, Huang B, He W, Zhang X Tags: J Autoimmun Source Type: research

Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers.
Abstract Thymomas are associated with a very high risk of developing Myasthenia Gravis (MG). Our objectives were to identify histological and biological parameters to allow early diagnosis of thymoma patients susceptible to developing MG. We conducted a detailed retrospective analysis from a patient database, searching for differences between patients with thymoma-associated MG (MGT, n = 409) and thymoma without MG (TOMA, n = 111) in comparison with nonthymomatous MG patients (MG, n = 1246). We also performed multiplex and single molecule arrays to measure the serum levels of cytokines in these groups ...
Source: Journal of Autoimmunity - October 5, 2019 Category: Allergy & Immunology Authors: Lefeuvre CM, Payet CA, Fayet OM, Maillard S, Truffault F, Bondet V, Duffy D, de Montpreville V, Ghigna MR, Fadel E, Mansuet-Lupo A, Alifano M, Validire P, Gossot D, Behin A, Eymard B, Berrih-Aknin S, Le Panse R Tags: J Autoimmun Source Type: research

Usual interstitial pneumonia in ANCA-associated vasculitis: A poor prognostic factor.
This study focused on the outcomes of ILD patients with associated AAV (AAV-ILD). METHODS: AAV-ILD (cases: microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) with ILD) were compared to AAV patients without ILD (controls). ILD was defined as a usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern. Two controls were matched to each case for age (>or ≤65 years), ANCA status (PR3-or MPO-positive) and creatininemia (≥or 65 years (hazard ratio (HR) 4.54; p 
Source: Journal of Autoimmunity - September 27, 2019 Category: Allergy & Immunology Authors: Maillet T, Goletto T, Beltramo G, Dupuy H, Jouneau S, Borie R, Crestani B, Cottin V, Blockmans D, Lazaro E, Naccache JM, Pugnet G, Nunes H, de Menthon M, Devilliers H, Bonniaud P, Puéchal X, Mouthon L, Bonnotte B, Guillevin L, Terrier B, Samson M, French Tags: J Autoimmun Source Type: research

Immune checkpoint molecules. Possible future therapeutic implications in autoimmune diseases.
Abstract During host immune response, an initial and sufficient activation is required to avoid infection and cancer, yet an excessive activation bears the risk of autoimmune reactivity and disease development. This fastidious balance of the immune system is regulated by co-stimulatory and co-inhibitory molecules, also known as immune checkpoints. Both excessive co-stimulation and insufficient co-inhibition can induce the activation and proliferation of autoreactive cells that may lead to the development of autoimmune diseases. During the last decade, a growing number of new immune checkpoint receptors and ligands...
Source: Journal of Autoimmunity - September 26, 2019 Category: Allergy & Immunology Authors: Huang C, Zhu HX, Yao Y, Bian ZH, Zheng YJ, Li L, Moutsopoulos HM, Gershwin ME, Lian ZX Tags: J Autoimmun Source Type: research

The challenges of primary biliary cholangitis: What is new and what needs to be done.
In conclusion, using interdisciplinary approaches, groundbreaking advances can be expected before long in respect to our understanding of the etiopathogenesis of PBC, with the ultimate aim of improving its treatment. PMID: 31548157 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 20, 2019 Category: Allergy & Immunology Authors: Terziroli Beretta-Piccoli B, Mieli-Vergani G, Vergani D, Vierling JM, Adams D, Alpini G, Banales JM, Beuers U, Björnsson E, Bowlus C, Carbone M, Chazouillères O, Dalekos G, De Gottardi A, Harada K, Hirschfield G, Invernizzi P, Jones D, Krawitt E, Lanzav Tags: J Autoimmun Source Type: research

Autoimmune epithelitis (Sj ögren's syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity.
Autoimmune epithelitis (Sjögren's syndrome); the impact of metabolic status of glandular epithelial cells on auto-immunogenicity. J Autoimmun. 2019 Sep 17;:102335 Authors: Katsiougiannis S, Tenta R, Skopouli FN Abstract It is well established that distinct cell metabolic alterations strongly contribute to the modulation of innate and adaptive immune responses. In the past decade the term immunometabolism has been introduced to describe the intracellular metabolic shifts of immune cells that lead to alterations of their functions. The pathogenesis of Sjögren's syndrome (SS), also referred to ...
Source: Journal of Autoimmunity - September 17, 2019 Category: Allergy & Immunology Authors: Katsiougiannis S, Tenta R, Skopouli FN Tags: J Autoimmun Source Type: research

Epstein Barr virus nuclear antigen 1 (EBNA-1) peptides recognized by adult multiple sclerosis patient sera induce neurologic symptoms in a murine model.
Abstract Multiple sclerosis (MS) is an autoimmune demyelinating disease with progressive neurodegeneration and complex etiology likely involving genetic and environmental factors. MS has been associated with Epstein Barr virus (EBV) infection, with patients often showing enhanced responses to EBV antigens. To determine whether abnormal EBV nuclear antigen-1 (EBNA-1) humoral immunity can serve as an initiator of autoimmune responses in MS, we investigated the fine specificities of the humoral immune response against EBNA-1 in MS patients using solid phase epitope mapping. Antibodies from MS patients recognized an E...
Source: Journal of Autoimmunity - September 9, 2019 Category: Allergy & Immunology Authors: Jog NR, McClain MT, Heinlen LD, Gross T, Towner R, Guthridge JM, Axtell RC, Pardo G, Harley JB, James JA Tags: J Autoimmun Source Type: research

Interactions among glomerulus infiltrating macrophages and intrinsic cells via cytokines in chronic lupus glomerulonephritis.
Abstract Inflammation plays a key role in the pathogenesis of lupus nephritis (LN) and inflammatory cytokines within the glomeruli are critical in this process. However, little information is available for the identities of the cell types that are primarily responsible for the production and function of the various cytokines. We have devised a novel method to visualize cytokine signals in the kidney by confocal microscopy and found that cytokine production within the glomerulus is cell type-specific and under translational control. In the lupus-prone NZM2328 mice with chronic glomerulonephritis, IL-6, IL-1β, ...
Source: Journal of Autoimmunity - September 5, 2019 Category: Allergy & Immunology Authors: Sung SJ, Fu SM Tags: J Autoimmun Source Type: research

Increased adenosine-to-inosine RNA editing in rheumatoid arthritis.
CONCLUSION: A previously unrecognized regulation and role of ADAR1p150-mediated A-to-I RNA editing in post-transcriptional control in RA underpins therapeutic response and fuels inflammatory gene expression, thus representing an interesting therapeutic target. PMID: 31493964 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 4, 2019 Category: Allergy & Immunology Authors: Vlachogiannis NI, Gatsiou A, Silvestris DA, Stamatelopoulos K, Tektonidou MG, Gallo A, Sfikakis PP, Stellos K Tags: J Autoimmun Source Type: research

Efficacy and safety of mycophenolate mofetil in patients with virus-negative lymphocytic myocarditis: A prospective cohort study.
Abstract BACKGROUND: virus-negative lymphocytic myocarditis (VNLM) is a severe inflammatory heart disease with elusive therapies. We aimed to assess the efficacy of mycophenolate-mofetil (MMF) in patients with VNLM. METHODS: patients were enrolled in this prospective cohort study and were treated with MMF, as the initial treatment in case of concomitant systemic immune diseases (SIDs), or as rescue therapy in isolated myocarditis intolerant/resistant to azathioprine. All were initially evaluated for endomyocardial biopsy; ECG, 24-h Holter, echocardiography, troponin T and NT-proBNP were obtained in all patien...
Source: Journal of Autoimmunity - September 2, 2019 Category: Allergy & Immunology Authors: De Luca G, Campochiaro C, Sartorelli S, Peretto G, Sala S, Palmisano A, Esposito A, Candela C, Basso C, Rizzo S, Thiene G, Della Bella P, Dagna L Tags: J Autoimmun Source Type: research

Lambda interferons in immunity and autoimmunity.
Abstract Type I IFNs are well known players in immunity and autoimmunity. They induce potent innate and adaptive immune responses essential for mediating host defenses against viral and bacterial infections but also driving inflammation during chronic inflammatory and autoimmune diseases. Lambda interferons (IFNλs) or type III IFNs, on the other hand, comprise a relatively new family of cytokines sharing homology and functional resemblance with type I IFNs but whose spectrum of activities remains poorly understood. Although IFNλs induce antiviral responses similar to type I IFNs, their restricted pat...
Source: Journal of Autoimmunity - August 31, 2019 Category: Allergy & Immunology Authors: Vlachiotis S, Andreakos E Tags: J Autoimmun Source Type: research

Autotaxin and chronic inflammatory diseases.
Abstract Autotaxin (ATX) is a secreted glycoprotein, widely present in biological fluids including blood. ATX catalyzes the hydrolysis of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a growth factor-like, signaling phospholipid. LPA exerts pleiotropic effects mediated by its G-protein-coupled receptors that are widely expressed and exhibit overlapping specificities. Although ATX also possesses matricellular properties, the majority of ATX reported functions in adulthood are thought to be mediated through the extracellular production of LPA. ATX-mediated LPA synthesis is likely localized at the cel...
Source: Journal of Autoimmunity - August 27, 2019 Category: Allergy & Immunology Authors: Magkrioti C, Galaris A, Kanellopoulou P, Stylianaki EA, Kaffe E, Aidinis V Tags: J Autoimmun Source Type: research

Genetic contributors and soluble mediators in prediction of autoimmune comorbidity.
Abstract Comorbidities including subclinical atherosclerosis, neuropsychological aberrations and lymphoproliferation represent a major burden among patients with systemic autoimmune diseases; they occur either as a result of intrinsic disease related characteristics including therapeutic interventions or traditional risk factors similar to those observed in general population. Soluble molecules recently shown to contribute to subclinical atherosclerosis in the context of systemic lupus erythematosus (SLE) include among others B-cell activating factor (BAFF), hyperhomocysteinemia, parathormone (PTH) levels and auto...
Source: Journal of Autoimmunity - August 20, 2019 Category: Allergy & Immunology Authors: Nezos A, Evangelopoulos ME, Mavragani CP Tags: J Autoimmun Source Type: research

Predictive markers of lymphomagenesis in Sj ögren's syndrome: From clinical data to molecular stratification.
Predictive markers of lymphomagenesis in Sjögren's syndrome: From clinical data to molecular stratification. J Autoimmun. 2019 Aug 17;:102316 Authors: Kapsogeorgou EK, Voulgarelis M, Tzioufas AG Abstract Sjögren's syndrome (SS) is a chronic systemic autoimmune disease, affecting predominantly the exocrine glands, a large array of systemic manifestations and high risk of lymphoma development. The latter constitutes the major adverse outcome of SS contributing in the increased morbidity and mortality of the disease. The vast majority of lymphomas in SS are B-cell non-Hodgkin's lymphomas (NHL),...
Source: Journal of Autoimmunity - August 17, 2019 Category: Allergy & Immunology Authors: Kapsogeorgou EK, Voulgarelis M, Tzioufas AG Tags: J Autoimmun Source Type: research

Balancing cancer immunotherapy and immune-related adverse events: The emerging role of regulatory T cells.
Abstract Advances in our understanding οf tumor immunity have prompted a paradigm shift in oncology, with the emergence of immunotherapy, where therapeutic agents are used to target immune cells rather than cancer cells. A real breakthrough in the field of immunotherapy came with the use of immune checkpoint inhibitors (ICI), namely antagonistic antibodies that block key immune regulatory molecules (checkpoint molecules), such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed cell death protein (PD-1) and its ligand PD-L1, that under physiologic conditions suppress T cell effector functio...
Source: Journal of Autoimmunity - August 14, 2019 Category: Allergy & Immunology Authors: Alissafi T, Hatzioannou A, Legaki AI, Varveri A, Verginis P Tags: J Autoimmun Source Type: research

Epigenetic perspectives on systemic autoimmune disease.
Abstract Autoimmune diseases are characterized by increased reactivity of the immune system towards self-antigens, causing tissue damage. Although their etiology remains largely unknown, genetic, microbial, environmental and psychological factors are recognized as contributing elements. Epigenetic changes, including covalent modifications of the DNA and histones, are critical signaling mediators between the genome and the environment, and thus potent regulators of cellular functions. The most extensively studied epigenetic modifications are Cytosine DNA methylation and histone acetylation and methylation on variou...
Source: Journal of Autoimmunity - August 14, 2019 Category: Allergy & Immunology Authors: Karagianni P, Tzioufas AG Tags: J Autoimmun Source Type: research

Activin-A in the regulation of immunity in health and disease.
Abstract The TGF-β superfamily of cytokines plays pivotal roles in the regulation of immune responses protecting against or contributing to diseases, such as, allergy, autoimmunity and cancer. Activin-A, a member of the TGF-β superfamily, was initially identified as an inducer of follicle-stimulating hormone secretion. Extensive research over the past decades illuminated fundamental roles for activin-A in essential biologic processes, including embryonic development, stem cell maintenance and differentiation, haematopoiesis, cell proliferation and tissue fibrosis. Activin-A signals through two type I and...
Source: Journal of Autoimmunity - August 12, 2019 Category: Allergy & Immunology Authors: Morianos I, Papadopoulou G, Semitekolou M, Xanthou G Tags: J Autoimmun Source Type: research

Driving towards Precision Medicine for angioedema without wheals.
Abstract Evidence accumulated over the last two decades indicates that recurrent angioedema without wheals constitutes a diverse family of disorders with a much higher complexity than was previously regarded. Indicatively, during the last two years, novel variants of three genes other than SERPING1 and F12 have been identified in association with hereditary angioedema. Most interestingly, functional studies of at least one of these variants (the variant c.807G > T of ANGPT1 gene) imply the existence of a new disease endotype in which the altered bradykinin metabolism and function does not play a central rol...
Source: Journal of Autoimmunity - August 9, 2019 Category: Allergy & Immunology Authors: Germenis AE, Cicardi M Tags: J Autoimmun Source Type: research

Phosphatidylethanolamine binding protein-4 (PEBP4) is increased in IgA nephropathy and is associated with IgA-positive B-cells in affected kidneys.
In this study, we used shotgun LC-MS/MS proteomics to compare small volumes of urine from healthy subjects and IgAN patients. We identified multiple urine proteins with unknown renal or IgAN function. Our attention was captured by the increase of phosphatidylethanolamine binding protein-4 (PEBP4) in IgAN urine. The function of PEBP4 in IgAN or renal disease is unknown. Increased levels of urine and serum PEBP4 were subsequently validated in different cohorts of IgAN patients and PEBP4 was linked to declining kidney function in IgAN. Strong PEBP4 staining was sporadically seen in IgAN kidney biopsies, colocalising with IgA ...
Source: Journal of Autoimmunity - August 8, 2019 Category: Allergy & Immunology Authors: Taylor S, Pieri K, Nanni P, Tica J, Barratt J, Didangelos A Tags: J Autoimmun Source Type: research

Autoantigens PLA2R and THSD7A in membranous nephropathy share a common epitope motif in the N-terminal domain.
Abstract Patients with membranous nephropathy have autoantibodies against PLA2R (up to 80%), or THSD7A (up to 2%). We previously described the immunodominant epitope within PLA2R but epitopes in THSD7A are still unknown. To find anti-THSD7A sera for this study, we screened 1843 sera from biopsy-proven MN patients by ELISA and identified 22 sera as anti-THSD7A positive representing 1.2% of MN cases. Anti-THSD7A positive sera were further characterized by western blotting and slot blotting on THSD7A protein fragments and peptides. Real time interaction analyses and antibodies off-rate could be reliably determined us...
Source: Journal of Autoimmunity - August 5, 2019 Category: Allergy & Immunology Authors: Fresquet M, Rhoden SJ, Jowitt TA, McKenzie EA, Roberts I, Lennon R, Brenchley PE Tags: J Autoimmun Source Type: research

Restricted myeloperoxidase epitopes drive the adaptive immune response in MPO-ANCA vasculitis.
CONCLUSIONS: These observations reveal interactions between restricted MPO epitopes and the adaptive immune system within ANCA vasculitis that may inform new antigen-specific therapies in autoimmune disease while providing insight into immunopathogenesis. PMID: 31383567 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 2, 2019 Category: Allergy & Immunology Authors: Free ME, Stember KG, Hess JJ, McInnis EA, Lardinois O, Hogan SL, Hu Y, Mendoza C, Le AK, Guseman AJ, Pilkinton MA, Bortone DS, Cowens K, Sidney J, Karosiene E, Peters B, James E, Kwok WW, Vincent BG, Mallal SA, Jennette JC, Ciavatta DJ, Falk RJ Tags: J Autoimmun Source Type: research

New insights in cryoglobulinemic vasculitis.
Abstract Cryoglobulins are antibodies that precipitate at low temperatures and dissolve after rewarming. Cryoglobulinemia refers to the presence of circulating cryoglobulins and generally leads to a systemic inflammatory syndrome characterized by fatigue, arthralgia, purpura, ulcers, neuropathy and/or glomerulonephritis. The disease mainly involves small to medium-sized blood vessels and causes vasculitis due to cryoglobulin-containing immune complexes. Cryoglobulinemia is classified into three types (I, II and III) on the basis of immunoglobulin composition. Predisposing conditions include lymphoproliferative, au...
Source: Journal of Autoimmunity - August 2, 2019 Category: Allergy & Immunology Authors: Silva F, Pinto C, Barbosa A, Borges T, Dias C, Almeida J Tags: J Autoimmun Source Type: research

Type I interferon gene expression in antiphospholipid syndrome: Pathogenetic, clinical and therapeutic implications.
Abstract Type I Interferon gene expression has been shown to play an important role in the pathogenesis of several systemic autoimmune disorders, paving the way for its potential use as a surrogate marker or a therapeutic tool. While the concept of type I interferon signature and its correlation with clinical phenotypes and disease activity, along with anti-interferon targeted therapy have been vastly investigated in patients with systemic lupus erythematosus, there is a paucity of data concerning antiphospholipid syndrome patients. In this review, we summarize the current knowledge on the pathogenetic and clinica...
Source: Journal of Autoimmunity - August 1, 2019 Category: Allergy & Immunology Authors: Xourgia E, Tektonidou MG Tags: J Autoimmun Source Type: research

A novel spleen-resident immature NK cell subset and its maturation in a T-bet-dependent manner.
Abstract NK cells are thought to develop primarily in the bone marrow during adult life. However, increasing evidence shows that NK cell developmental intermediates can be found in different peripheral tissues with unique characteristics. Here, we identified a unique NK cell subset with the CD49a-CD49b- phenotype in the spleen. These cells displayed an immature phenotype and weak abilities in cytotoxicity and cytokine production. Adoptive transfer experiments revealed that they could develop into mature conventional NK (cNK) cells. Transcriptome analysis further confirmed their immature features. Parabiosis experi...
Source: Journal of Autoimmunity - July 24, 2019 Category: Allergy & Immunology Authors: Wang B, Zhou J, Chen Y, Wei H, Sun R, Tian Z, Peng H Tags: J Autoimmun Source Type: research

Changing epidemiology of immune-mediated inflammatory diseases in immigrants: A systematic review of population-based studies.
CONCLUSION: Based on our systematic review, the epidemiology of IMIDs among immigrants varies according to native and host countries, immigrant generation, and IMID type. The rapid evolution suggests a role for non-genetic factors and gene-environment interactions. Future studies should focus on these pattern shifts, given implications of rising global burden of IMIDs and immigration. PMID: 31351784 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 24, 2019 Category: Allergy & Immunology Authors: Agrawal M, Shah S, Patel A, Pinotti R, Colombel JF, Burisch J Tags: J Autoimmun Source Type: research

Autoinflammation: Lessons from the study of familial Mediterranean fever.
Abstract Autoinflammatory disorders represent a heterogeneous group of systemic inflammatory diseases caused by genetic or acquired defects in key components of the innate immunity. Familial Mediterranean fever (FMF) is the most common among the other clinical phenotypes of the rare hereditary periodic fevers (HPFs) syndromes. FMF is associated with mutations in the MEFV gene encoding pyrin and is characterized by recurrent, often stress-provoked attacks of fever and serositis, but sometimes also by chronic subclinical inflammation. FMF is prevalent in Greece and other countries of the eastern Mediterranean region...
Source: Journal of Autoimmunity - July 20, 2019 Category: Allergy & Immunology Authors: Skendros P, Papagoras C, Mitroulis I, Ritis K Tags: J Autoimmun Source Type: research

Chaperones may cause the focus of diabetes autoimmunity on distinct (pro)insulin peptides.
Abstract It is still an enigma why T cell autoreactivity in type 1 diabetes targets few beta cell antigens only. Among these, one primary autoantigen is pro(insulin). Autoimmune T cells preferentially recognise three epitopes on the proinsulin molecule, of which the peptide region B:11-23 is the dominant one. Interestingly, the three regions superimpose with binding sites of the chaperone hsp70, the region B:11-23 being the strongest binding one. Absence of an intact core region B:15-17 prevents autoimmune diabetes in NOD as well as binding of hsp70. A role of hsp70 in selecting autoimmune epitopes is supported by...
Source: Journal of Autoimmunity - July 18, 2019 Category: Allergy & Immunology Authors: Kolb H, Burkart V Tags: J Autoimmun Source Type: research

Bystander activation and autoimmunity.
Abstract The interaction over time of genetic, epigenetic and environmental factors (i.e., autoimmune ecology) increases or decreases the liability an individual would have to develop an autoimmune disease (AD) depending on the misbalance between risk and protective effects. Pathogens have been the most common antecedent events studied, but multiple other environmental factors including xenobiotic chemicals, drugs, vaccines, and nutritional factors have been implicated into the development of ADs. Three main mechanisms have been offered to explain the development of autoimmunity: molecular mimicry, epitope spreadi...
Source: Journal of Autoimmunity - July 17, 2019 Category: Allergy & Immunology Authors: Pacheco Y, Acosta-Ampudia Y, Monsalve DM, Chang C, Gershwin ME, Anaya JM Tags: J Autoimmun Source Type: research

Inflammasomes and autoimmune and rheumatic diseases: A comprehensive review.
Abstract Inflammasomes are a multi-protein platform forming a part of the innate immune system. Inflammasomes are at standby status and can be activated when needed. Inflammasome activation is an important mechanism for the production of active interleukin (IL)-1β and IL-18, which have important roles to instruct adaptive immunity. Active forms of inflammasomes trigger a series of inflammatory cascades and lead to the differentiation and polarization of naïve T cells and secretion of various cytokines, which can induce various kinds of autoimmune and rheumatic diseases such as systemic lupus erythematosu...
Source: Journal of Autoimmunity - July 17, 2019 Category: Allergy & Immunology Authors: Shin JI, Lee KH, Joo YH, Lee JM, Jeon J, Jung HJ, Shin M, Cho S, Kim TH, Park S, Jeon BY, Jeong H, Lee K, Kang K, Oh M, Lee H, Lee S, Kwon Y, Oh GH, Kronbichler A Tags: J Autoimmun Source Type: research

The association of serum interleukin-6 levels with clinical outcomes in antineutrophil cytoplasmic antibody-associated vasculitis.
Abstract OBJECTIVE: To investigate serum IL-6 (sIL-6) levels during active disease, complete remission (CR), and relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), and to explore the association of changes in sIL-6 with clinical outcomes. METHODS: sIL-6 levels were measured at baseline and longitudinally over 18 months, in 78 patients with AAV enrolled in a randomized controlled trial comparing treatment with either rituximab (RTX) or cyclophosphamide (CYC)/azathioprine (AZA). Outcome variables included baseline clinical features, ANCA specificity, disease activity (active dise...
Source: Journal of Autoimmunity - July 15, 2019 Category: Allergy & Immunology Authors: Berti A, Warner R, Johnson K, Cornec D, Schroeder DR, Kabat BF, Langford CA, Kallenberg CGM, Seo P, Spiera RF, St Clair EW, Fervenza FC, Stone JH, Monach PA, Specks U, Merkel PA, RAVE-ITN Research Group Tags: J Autoimmun Source Type: research

Cellular aging over 13 years associated with incident antinuclear antibody positivity in the Baltimore Longitudinal Study of Aging.
This study aims to evaluate whether shorter peripheral blood mononuclear cell (PBMC) telomere length, a marker of more advanced biological age, is associated with ANA positivity prevalence and incidence in middle and older aged autoimmune disease-free individuals from the Baltimore Longitudinal Study of Aging (BLSA). Telomere length was measured by Southern Blot and categorized into tertiles. ANA was measured in a 1:80 and a 1:160 dilution of sera by immunofluorescence using HEp-2 cells (seropositive = 3 or 4). Multiple logistic regression was used to estimate the odds ratios and 95% confidence intervals of ANA posit...
Source: Journal of Autoimmunity - July 11, 2019 Category: Allergy & Immunology Authors: Meier HCS, Parks CG, Liu HB, Sandler DP, Simonsick EM, Deane K, Weng NP Tags: J Autoimmun Source Type: research

Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity.
Abstract Eos (lkzf4) is a member of the Ikaros family of transcription factors and is preferentially expressed in T-regulatory (Treg) cells. However, the role of Eos in Treg function is controversial. One study using siRNA knock down of Eos demonstrated that it was critical for Treg suppressor function. In contrast, Treg from mice with a global deficiency of Eos had normal Treg function in vitro and in vivo. To further dissect the function of Eos in Tregs, we generated mice with a conditional knock out of Eos in Treg cells (lkzf4fl/fl X Foxp3YFP-cre, Eos cKO). Deletion of Eos in Treg resulted in activation of CD4+...
Source: Journal of Autoimmunity - July 8, 2019 Category: Allergy & Immunology Authors: Gokhale AS, Gangaplara A, Lopez-Occasio M, Thornton AM, Shevach EM Tags: J Autoimmun Source Type: research

Predicting drug-free remission in rheumatoid arthritis: A prospective interventional cohort study.
CONCLUSION: We provide proof-of-concept evidence for predictors of drug-free remission in RA. If validated, these biomarkers could help to personalize immunosuppressant withdrawal: a therapy paradigm shift with ensuing patient and economic benefits. PMID: 31280933 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 4, 2019 Category: Allergy & Immunology Authors: Baker KF, Skelton AJ, Lendrem DW, Scadeng A, Thompson B, Pratt AG, Isaacs JD Tags: J Autoimmun Source Type: research

PD-1 aborts the activation trajectory of autoreactive CD8+ T cells to prohibit their acquisition of effector functions.
Abstract Anti-PD-1 therapy can induce eradication of tumors and immune-related adverse events (irAEs) in humans and model animals. However, how anti-PD-1 therapy modifies cellular phenotypes of CD8+ T cells to destroy tumors and damage self-tissues remains to be clarified. Here we performed single cell mRNA expression profiling of autoreactive CD8+ T cells under or beyond PD-1 suppression in target tissues and reconstructed their activation trajectory. Autoreactive CD8+ T cells went through four activation phases and PD-1 strongly attenuated the transition from the second- to the third-phase, where effector functi...
Source: Journal of Autoimmunity - July 2, 2019 Category: Allergy & Immunology Authors: Okamura H, Okazaki IM, Shimizu K, Maruhashi T, Sugiura D, Mizuno R, Okazaki T Tags: J Autoimmun Source Type: research

Extracellular traps and PAD4 released by macrophages induce citrullination and auto-antibody production in autoimmune arthritis.
Abstract The mechanisms underlying the transition of rheumatoid arthritis (RA) systemic autoimmunity to the joints remain largely unknown. Here, we demonstrate that macrophages in the secondary lymphoid organs (SLOs) and synovial ectopic lymphoid-like structures (ELSs) express peptidylarginine deiminase 4 (PAD4) in murine collagen induced arthritis (CIA) and synovial biopsies from RA patients. Moreover, peptidyl citrulline colocalized with macrophages in SLOs and ELSs, and depletion of macrophages in CIA decreased lymphoid tissue citrullination and serum anti-citrullinated protein/peptide antibody (ACPA) levels. F...
Source: Journal of Autoimmunity - July 2, 2019 Category: Allergy & Immunology Authors: El Shikh MEM, El Sayed R, Nerviani A, Goldmann K, John CR, Hands R, Fossati-Jimack L, Lewis MJ, Pitzalis C Tags: J Autoimmun Source Type: research

Monocytes contribute to DNA sensing through the TBK1 signaling pathway in type 1 diabetes patients.
CONCLUSIONS: Here, we show that there were significant differences in DNA sensing in T1D patients compared to that in controls. We demonstrate that monocytes from T1D patients are able to sense microbial- and self-DNA, leading to proinflammatory cytokine secretion through the adaptor protein STING and the TBK1 kinase. PMID: 31256920 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 27, 2019 Category: Allergy & Immunology Authors: Zentsova I, Parackova Z, Kayserova J, Palova-Jelinkova L, Vrabcova P, Volfova N, Sumnik Z, Pruhova S, Petruzelkova L, Sediva A Tags: J Autoimmun Source Type: research

Cytotoxic KLRG1 expressing lymphocytes invade portal tracts in primary biliary cholangitis.
Conclusion: Highly cytotoxic KLRG1+ lymphocytes have invaded PBC liver portal areas. Liver KLRG1 gene expression and the abundance of KLRG1+ lymphocytes are positively correlated with disease biomarkers used as clinical trial outcome measures (liver transplantation and serum alkaline phosphatase), suggesting the targeting of KLRG1+ lymphocytes as a rational approach for PBC therapeutic drug development. PMID: 31255417 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 26, 2019 Category: Allergy & Immunology Authors: Li Y, Li B, You Z, Zhang J, Wei Y, Li Y, Chen Y, Huang B, Wang Q, Miao Q, Peng Y, Fang J, Gershwin ME, Tang R, Greenberg SA, Ma X Tags: J Autoimmun Source Type: research

CAPS criteria fail to identify most severely-ill thrombotic antiphospholipid syndrome patients requiring intensive care unit admission.
CONCLUSIONS: In this study, CAPS criteria were not associated with mortality of thrombotic APS patients requiring ICU admission. Further studies are need evaluate the adequacy of CAPS criteria for critically-ill APS patients. PMID: 31253464 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 25, 2019 Category: Allergy & Immunology Authors: Pineton de Chambrun M, Larcher R, Pène F, Argaud L, Demoule A, Jamme M, Coudroy R, Mathian A, Gibelin A, Azoulay E, Tandjaoui-Lambiotte Y, Dargent A, Beloncle FM, Raphalen JH, Couteau-Chardon A, de Prost N, Devaquet J, Contou D, Gaugain S, Trouiller P, G Tags: J Autoimmun Source Type: research

Ultraviolet light induces increased T cell activation in lupus-prone mice via type I IFN-dependent inhibition of T regulatory cells.
Abstract Ultraviolet (UV) light is a known trigger of skin and possibly systemic inflammation in systemic lupus erythematosus (SLE) patients. Although type I interferons (IFN) are upregulated in SLE skin after UV exposure, the mechanisms to explain increased UVB-induced inflammation remain unclear. This paper compares the role of type I IFNs in regulating immune cell activation between wild-type and lupus-prone mice following UVB exposure. 10-week old female lupus-prone (NZM2328), wild-type (BALB/c) and iNZM mice (lack a functional type I IFN receptor on NZM2328 background) were treated on their dorsal skin with 1...
Source: Journal of Autoimmunity - June 24, 2019 Category: Allergy & Immunology Authors: Wolf SJ, Estadt SN, Theros J, Moore T, Ellis J, Liu J, Reed TJ, Jacob CO, Gudjonsson JE, Kahlenberg JM Tags: J Autoimmun Source Type: research

Targeting CD34+ cells of the inflamed synovial endothelium by guided nanoparticles for the treatment of rheumatoid arthritis.
cor P Abstract Despite the advances in the treatment of rheumatoid arthritis (RA) achieved in the last few years, several patients are diagnosed late, do not respond to or have to stop therapy because of inefficacy and/or toxicity, leaving still a huge unmet need. Tissue-specific strategies have the potential to address some of these issues. The aim of the study is the development of a safe nanotechnology approach for tissue-specific delivery of drugs and diagnostic probes. CD34 + endothelial precursors were addressed in inflamed synovium using targeted biodegradable nanoparticles (tBNPs). These nanostructures...
Source: Journal of Autoimmunity - June 15, 2019 Category: Allergy & Immunology Authors: Colombo F, Durigutto P, De Maso L, Biffi S, Belmonte B, Tripodo C, Oliva R, Bardini P, Marini GM, Terreno E, Pozzato G, Rampazzo E, Bertrand J, Feuerstein B, Javurek J, Havrankova J, Pitzalis C, Nuñez L, Meroni P, Tedesco F, Sblattero D, Macor P Tags: J Autoimmun Source Type: research

Myeloid sphingosine-1-phosphate receptor 1 is important for CNS autoimmunity and neuroinflammation.
In this study, we demonstrate that S1P1-mediated TH17 polarization is not an intrinsic T cell effect, but dependent on sustained S1P1 signaling in myeloid cells. First, utilizing the S1P1(S5A) mice in the EAE model, we observed that S1P1 activated and enhanced antigen presentation function in myeloid cells. Second, sequential phosphorylation of STAT3 occurred in dendritic cells, monocytes, and macrophages/microglia during neuroinflammation. Third, we show that pro-inflammatory (CD45hiCD11b+Ly6Chi) monocytes contribute to TH17 differentiation and neuroinflammation by regulating IL-6 expression. Finally, results from experim...
Source: Journal of Autoimmunity - June 12, 2019 Category: Allergy & Immunology Authors: Tsai HC, Nguyen K, Hashemi E, Engleman E, Hla T, Han MH Tags: J Autoimmun Source Type: research

Analysis of the PD-1/PD-L1 axis in human autoimmune thyroid disease: Insights into pathogenesis and clues to immunotherapy associated thyroid autoimmunity.
In conclusions 1) the PD-1/PD-L1 pathway is activated in AITD glands but probably not to the extent to inhibit disease progression and 2) Thyroid autoimmunity arising after PD-1/PD-L1 blocking therapies in cancer patients may result from interfering PD-1/PD-L1 tolerance mechanism in thyroid with minimal (focal) thyroiditis. Finally acting on the PD-1/PD-L1 pathway could be a new approach to treat AITD and other organ-specific autoimmunity in the future. PMID: 31182340 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 7, 2019 Category: Allergy & Immunology Authors: Álvarez-Sierra D, Marín-Sánchez A, Ruiz-Blázquez P, de Jesús Gil C, Iglesias-Felip C, González Ó, Casteras A, Costa RF, Nuciforo P, Colobran R, Pujol-Borrell R Tags: J Autoimmun Source Type: research

Regulatory T cells engineered with a novel insulin-specific chimeric antigen receptor as a candidate immunotherapy for type 1 diabetes.
Abstract Adoptive immunotherapy with ex vivo expanded, polyspecific regulatory T cells (Tregs) is a promising treatment for graft-versus-host disease. Animal transplantation models used by us and others have demonstrated that the adoptive transfer of allospecific Tregs offers greater protection from graft rejection than that of polyclonal Tregs. This finding is in contrast to those of autoimmune models, where adoptive transfer of polyspecific Tregs had very limited effects, while antigen-specific Tregs were promising. However, antigen-specific Tregs in autoimmunity cannot be isolated in sufficient numbers. Chimeri...
Source: Journal of Autoimmunity - June 5, 2019 Category: Allergy & Immunology Authors: Tenspolde M, Zimmermann K, Weber LC, Hapke M, Lieber M, Dywicki J, Frenzel A, Hust M, Galla M, Buitrago-Molina LE, Manns MP, Jaeckel E, Hardtke-Wolenski M Tags: J Autoimmun Source Type: research

Impact of anti-CASPR2 autoantibodies from patients with autoimmune encephalitis on CASPR2/TAG-1 interaction and Kv1 expression.
raz N Abstract Autoantibodies against CASPR2 (contactin-associated protein-like 2) have been linked to autoimmune limbic encephalitis that manifests with memory disorders and temporal lobe seizures. According to the growing number of data supporting a role for CASPR2 in neuronal excitability, CASPR2 forms a molecular complex with transient axonal glycoprotein-1 (TAG-1) and shaker-type voltage-gated potassium channels (Kv1.1 and Kv1.2) in compartments critical for neuronal activity and is required for Kv1 proper positioning. Whereas the perturbation of these functions could explain the symptoms observed in patients...
Source: Journal of Autoimmunity - June 5, 2019 Category: Allergy & Immunology Authors: Saint-Martin M, Pieters A, Déchelotte B, Malleval C, Pinatel D, Pascual O, Karagogeos D, Honnorat J, Pellier-Monnin V, Noraz N Tags: J Autoimmun Source Type: research

The proteasome activator REG γ counteracts immunoproteasome expression and autoimmunity.
The proteasome activator REGγ counteracts immunoproteasome expression and autoimmunity. J Autoimmun. 2019 Jun 03;: Authors: Yao L, Zhou L, Xuan Y, Zhang P, Wang X, Wang T, Meng T, Xue Y, Ma X, Shah AS, Shang S, Ma X, Xie W, Wang H, Fu Q, Xia Y, Moses RE, Wang H, Li L, Xiao J, Zhang B, Li X Abstract For quite a long time, the 11S proteasome activator REGɑ and REGβ, but not REGγ, are known to control immunoproteasome and promote antigen processing. Here, we demonstrate that REGγ functions as an inhibitor for immunoproteasome and autoimmune disease. Depletion of REGγ promote...
Source: Journal of Autoimmunity - June 3, 2019 Category: Allergy & Immunology Authors: Yao L, Zhou L, Xuan Y, Zhang P, Wang X, Wang T, Meng T, Xue Y, Ma X, Shah AS, Shang S, Ma X, Xie W, Wang H, Fu Q, Xia Y, Moses RE, Wang H, Li L, Xiao J, Zhang B, Li X Tags: J Autoimmun Source Type: research

Adipocytes orchestrate the formation of tertiary lymphoid organs in the creeping fat of Crohn's disease affected mesentery.
Abstract The formation of tertiary lymphoid organs (TLOs) is orchestrated by the stromal cells of tissues chronically submitted to inflammatory stimuli, in order to uphold specific adaptive immune responses. We have recently shown that the smooth muscle cells of the arterial wall orchestrate the formation of the TLOs associated with atherosclerosis in response to the local release of TNF-α. Observational studies have recently documented the presence of structures resembling TLOs the creeping fat that develops in the mesentery of patients with Crohn's disease (CD), an inflammatory condition combining a comple...
Source: Journal of Autoimmunity - June 3, 2019 Category: Allergy & Immunology Authors: Guedj K, Abitbol Y, Cazals-Hatem D, Morvan M, Maggiori L, Panis Y, Bouhnik Y, Caligiuri G, Corcos O, Nicoletti A Tags: J Autoimmun Source Type: research

DNGR1-mediated deletion of A20/Tnfaip3 in dendritic cells alters T and B-cell homeostasis and promotes autoimmune liver pathology.
Abstract Dendritic cells (DCs) are central regulators of tolerance versus immunity. The outcome depends amongst others on DC subset and activation status. Whereas CD11b+ type 2 conventional DCs (cDC2s) initiate proinflammatory helper T (Th)-cell responses, CD103+ cDC1s are crucial for regulatory T-cell (Treg) induction and CD8+ T-cell activation. DC activation is controlled by the transcription factor NF-κB. Ablation of A20/Tnfaip3, a critical regulator of NF-κB activation, in DCs leads to constitutive DC activation and development of systemic autoimmunity. We hypothesized that the activation status of...
Source: Journal of Autoimmunity - May 28, 2019 Category: Allergy & Immunology Authors: Das T, Bergen IM, Koudstaal T, van Hulst JAC, van Loo G, Boonstra A, Vanwolleghem T, Leung PSC, Gershwin ME, Hendriks RW, Kool M Tags: J Autoimmun Source Type: research

Obstetric and neonatal complications among women with autoimmune disease.
CONCLUSION(S): Despite the heterogeneity in autoimmune diseases, we observed elevated preterm birth risk for most women with autoimmune disease. SLE and T1DM appeared to confer increased risk for a wide range of adverse outcomes. PMID: 31147159 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 27, 2019 Category: Allergy & Immunology Authors: Williams A, Grantz K, Seeni I, Robledo C, Li S, Ouidir M, Nobles C, Mendola P Tags: J Autoimmun Source Type: research

Pathogenesis of lupus nephritis: RIP3 dependent necroptosis and NLRP3 inflammasome activation.
In this study, RIP3 and necroptosis pathway activations were demonstrated in podocytes in renal biopsies from patients with class IV LN and in the diseased kidneys from lupus-prone NZM2328 and MRL/lpr mice. RIP3 activation was accompanied with the activation of MLKL, the effector molecule of the necroptosis pathway, and activation of caspase-1, the effector of the NLRP3 inflammasome pathway. Podocyte activation of RIP3 was detected readily with the development of LN in NZM2328 mice, suggesting this activation may play a significant role in the pathogenesis of LN. GSK872, a RIP3 specific inhibitor, inhibited the development...
Source: Journal of Autoimmunity - May 24, 2019 Category: Allergy & Immunology Authors: Guo C, Fu R, Zhou M, Wang S, Huang Y, Hu H, Zhao J, Gaskin F, Yang N, Fu SM Tags: J Autoimmun Source Type: research