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Journal of Autoimmunity

Alexandra Audemard-Verger, Evangéline Pillebout, Agnès Jamin, Laureline Berthelot, Cédric Aufray, Bruno Martin, Aurélie Sannier, Eric Daugas, Julie Déchanet-Merville, Yolande Richard, Renato Monteiro, Bruno Lucas
OBJECTIVES: Adult immunoglobulin A vasculitis (IgAV) is an immune complex small vessel vasculitis. So far, the involvement of T cells in this pathology has been poorly studied. The aim of this study was to analyze T-cell homeostasis as well as cytokine and chemokine concentrations in the blood and tissues of IgAV patients. METHODS: T cells, cytokine and chemokine concentrations were analyzed in peripheral blood using flow cytometry and multiplex assays. T-cell infiltrates in the kidney and the skin were characterized by immunohistochemistry...
February 8, 2019: Journal of Autoimmunity
Aaron Pariente, Alexis Guédon, Sonia Alamowitch, Sara Thietart, Fabrice Carrat, Stephen Delorme, Jean Capron, Carlotta Cacciatore, Michael Soussan, Azeddine Dellal, Olivier Fain, Arsene Mekinian
Acute cerebrovascular ischemic events are a rare and severe complication of giant cell arteritis (GCA). We aimed to determine the prevalence of GCA-related stroke, the overall survival and the relapse-free survival in patients with GCA. A multicentric retrospective analysis was performed on 129 patients with GCA diagnosed between September 2010 and October 2018 in two University Hospitals. Among 129 GCA patients, 18 (16%) presented an acute ischemic cerebrovascular event. Patients with stroke were older (83 [67-96] years versus 76 [58-96]; p = 0...
February 5, 2019: Journal of Autoimmunity
Chunyan Sun, Xiao Xiao, Li Yan, Li Sheng, Qixia Wang, Pan Jiang, Min Lian, Yanmei Li, Yiran Wei, Jun Zhang, Yong Chen, Bo Li, You Li, Binyuan Huang, Yikang Li, Yanshen Peng, Xiaoyu Chen, Jingyuan Fang, Dekai Qiu, Jing Hua, Ruqi Tang, Patrick Leung, M Eric Gershwin, Qi Miao, Xiong Ma
BACKGROUND AND AIMS: The most highly directed and specific autoantibody in human immunopathology is the serologic hallmark of primary biliary cholangitis (PBC), antimitochondrial antibodies (AMAs). However the clinical significance of finding a positive AMA, with normal alkaline phosphatase (ALP) remains enigmatic. METHODS: We took advantage of 169 consecutive outpatients who were identified as having a positive AMA, but normal ALP levels between January 2012 and January 2018...
January 29, 2019: Journal of Autoimmunity
Matthieu Ribon, Sarra Seninet, Julie Mussard, Mireille Sebbag, Cyril Clavel, Guy Serre, Marie-Christophe Boissier, Luca Semerano, Patrice Decker
OBJECTIVE: Neutrophil extracellular traps (NET), produced by activated polymorphonuclear neutrophils (PMN), are supposed to play a role in the pathogenesis of rheumatoid arthritis (RA), a chronic inflammatory autoimmune disease characterized by anti-citrullinated protein antibodies (ACPA). Indeed, NET contain citrullinated autoantigens and some RA autoantibodies recognize NET. However, the mechanisms by which NET trigger or perpetuate the inflammatory process in RA are hitherto not elucidated...
January 28, 2019: Journal of Autoimmunity
M Pellicciotta, R Rigoni, E L Falcone, S M Holland, A Villa, B Cassani
Primary immunodeficiencies (PIDs) are inherited disorders of the immune system, associated with a considerable increase in susceptibility to infections. PIDs can also predispose to malignancy, inflammation and autoimmunity. There is increasing awareness that some aspects of the immune dysregulation in PIDs may be linked to intestinal microbiota. Indeed, the gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both locally and systemically. Recent studies have indicated that genetic defects causing PIDs lead to perturbations in the conventional mechanisms underlying homeostasis in the gut, resulting in poor immune surveillance at the intestinal barrier, which associates with altered intestinal permeability and bacterial translocation...
January 28, 2019: Journal of Autoimmunity
Begum Horuluoglu, Defne Bayik, Neslihan Kayraklioglu, Emilie Goguet, Mariana J Kaplan, Dennis M Klinman
Systematic Lupus Erythematosus (SLE) is an autoimmune syndrome of unclear etiology. While T and B cell abnormalities contribute to disease pathogenesis, recent work suggests that inflammatory M1-like macrophages also play a role. Previous work showed that the TLR2/1 agonist PAM3CSK4 (PAM3) could stimulate normal human monocytes to preferentially differentiate into immunosuppressive M2-like rather than inflammatory M1-like macrophages. This raised the possibility of PAM3 being used to normalize the M1:M2 ratio in SLE...
January 21, 2019: Journal of Autoimmunity
Stefania Croci, Martina Bonacini, Francesco Muratore, Andrea Caruso, Antonio Fontana, Luigi Boiardi, Alessandra Soriano, Alberto Cavazza, Luca Cimino, Lucia Belloni, Ori Perry, Mati Fridkin, Maria Parmeggiani, Miri Blank, Yehuda Shoenfeld, Carlo Salvarani
Tuftsin-PhosphorylCholine (TPC) is a novel bi-specific molecule which links tuftsin and phosphorylcholine. TPC has shown immunomodulatory activities in experimental mouse models of autoimmune diseases. We studied herein the effects of TPC ex vivo on both peripheral blood mononuclear cells (PBMCs) and temporal artery biopsies (TABs) obtained from patients with giant cell arteritis (GCA) and age-matched disease controls. GCA is an immune-mediated disease affecting large vessels. Levels of 18 cytokines in supernatants, PBMC viability, T helper (Th) cell differentiation of PBMCs and gene expression in TABs were analyzed...
January 9, 2019: Journal of Autoimmunity
Carlotta De Filippo, Monica Di Paola, Teresa Giani, Francesca Tirelli, Rolando Cimaz
Microbial diversity plays a key role in the maintenance of intestinal homeostasis and in the development of the immune system in the gut mucosa. Maybe one of the most important function of our gut microbiota is the immune system education, in particular the discrimination of friends from foes that occurs during childhood. In addition to bacterial antigens, several metabolites of microbial origin have a crucial role in training of the immune system, such as Short Chain Fatty Acids (SCFAs). There are many evidences on the role of the gut microbiota in rheumatic diseases, in particular modifications of microbiota composition causing dysbiosis that, in turn, can induce gut permeability, and thus immunological imbalance and trigger inflammation...
January 9, 2019: Journal of Autoimmunity
Christina Seitz, Sang Liu, Katrin Klocke, Anne-Laure Joly, Paulo V Czarnewski, Christopher A Tibbitt, Sara M Parigi, Lisa S Westerberg, Jonathan M Coquet, Eduardo J Villablanca, Kajsa Wing, John Andersson
CTLA-4 is required for CD4+ Foxp3+ regulatory T (Treg) cell function, but its mode of action remains incompletely defined. Herein we generated Ctla-4ex2fl/fl Foxp3-Cre mice with Treg cells exclusively expressing a naturally occurring, ligand-independent isoform of CTLA-4 (liCTLA-4) that cannot interact with the costimulatory molecules CD80 and CD86. The mice did not exhibit any signs of effector T cell activation early in life, however, at 6 months of age they exhibited excessive T cell activation and inflammation in lungs...
January 4, 2019: Journal of Autoimmunity
Samantha A Chalmers, Sayra J Garcia, Joshua A Reynolds, Leal Herlitz, Chaim Putterman
Immune-mediated glomerulonephritis is a serious end organ pathology that commonly affects patients with systemic lupus erythematosus (SLE). A classic murine model used to study lupus nephritis (LN) is nephrotoxic serum nephritis (NTN), in which mice are passively transferred nephrotoxic antibodies. We have previously shown that macrophages are important in the pathogenesis of LN. To further investigate the mechanism by which macrophages contribute to the pathogenic process, and to determine if this contribution is mediated by NF-κB signaling, we created B6 mice which had RelA knocked out in myeloid cells, thus inhibiting classical NF-κB signaling in this cell lineage...
January 3, 2019: Journal of Autoimmunity
Melissa J Mulla, Monica C Pasternak, Jane E Salmon, Lawrence W Chamley, Vikki M Abrahams
Women with antiphospholipid antibodies (aPL) are at high risk for pregnancy complications, such as preeclampsia. We previously demonstrated that aPL recognizing β2 GPI promote an extravillous trophoblast pro-inflammatory, anti-migratory and anti-angiogenic profile similar to that seen in preeclampsia. Since preeclampsia in the absence of aPL may have an underlying infectious element, women with aPL may be at increased risk for preeclampsia or other adverse outcomes if an infection is present. Our objective was to determine the impact the common bacterial component, muramyl dipeptide (MDP), has on trophoblast responses to aPL...
December 26, 2018: Journal of Autoimmunity
Takuro Nii, Kentaro Kuzuya, Daijiro Kabata, Toshihiro Matsui, Atsuko Murata, Takeshi Ohya, Hidetoshi Matsuoka, Takashi Shimizu, Eri Oguro, Yasutaka Okita, Chikako Udagawa, Maiko Yoshimura, Eriko Kudo-Tanaka, Satoru Teshigawara, Yoshinori Harada, Yuji Yoshida, Kentaro Isoda, So-Ichiro Tsuji, Shiro Ohshima, Jun Hashimoto, Ayumi Shintani, Yasuo Takehana, Shigeto Tohma, Yukihiko Saeki
OBJECTIVES: To examine the influence of smoking on biologics treatment against different therapeutic targets, such as TNFα, IL-6, and T cell, in rheumatoid arthritis (RA) and elucidate the underlying molecular mechanism. METHODS: The association between drug-discontinuation due to poor therapeutic response and smoking status was analyzed individually in biologics against different therapeutic targets by a multivariable logistic regression analysis using the "NinJa" Registry, one of the largest cohorts of Japanese RA patients...
December 24, 2018: Journal of Autoimmunity
José A Villegas, Alexandra C Bayer, Katia Ider, Jacky Bismuth, Frédérique Truffault, Régine Roussin, Nicola Santelmo, Rozen Le Panse, Sonia Berrih-Aknin, Nadine Dragin
IL-23/Th17 pathway has been identified to sustain inflammatory condition in several autoimmune diseases and therefore being targeted in various therapeutic and effective approaches. Patients affected with autoimmune myasthenia gravis exhibit a disease effector tissue, the thymus, that harbors ectopic germinal centers that sustain production of auto-antibodies, targeting proteins located in the neuromuscular junction, cause of the organ-specific chronic autoimmune disease. The present study aims to investigate the IL-23/Th17 cell pathway in the thymic inflammatory and pathogenic events...
December 18, 2018: Journal of Autoimmunity
Teontor Simakou, John P Butcher, Stuart Reid, Fiona L Henriquez
Alopecia areata is an autoimmune disease that results in non-scarring hair loss, and it is clinically characterised by small patches of baldness on the scalp and/or around the body. It can later progress to total loss of scalp hair (Alopecia totalis) and/or total loss of all body hair (Alopecia universalis). The rapid rate of hair loss and disfiguration caused by the condition causes anxiety on patients and increases the risks of developing psychological and psychiatric complications. Hair loss in alopecia areata is caused by lymphocytic infiltrations around the hair follicles and IFN-γ...
December 15, 2018: Journal of Autoimmunity
M Saeed Qureshi, Jawaher Alsughayyir, Manu Chhabra, Jason M Ali, Martin J Goddard, Chris Devine, Thomas M Conlon, Michelle A Linterman, Reza Motallebzadeh, Gavin J Pettigrew
The development of humoral autoimmunity following organ transplantation is increasingly recognised, but of uncertain significance. We examine whether autoimmunity contributes independently to allograft rejection. In a MHC class II-mismatched murine model of chronic humoral rejection, we report that effector antinuclear autoantibody responses were initiated upon graft-versus-host allorecognition of recipient B cells by donor CD4 T-cells transferred within heart allografts. Consequently, grafts were rejected more rapidly, and with markedly augmented autoantibody responses, upon transplantation of hearts from donors previously primed against recipient...
December 6, 2018: Journal of Autoimmunity
Anje Cauwels, Sandra Van Lint, Dominiek Catteeuw, Shengru Pang, Franciane Paul, Elke Rogge, Annick Verhee, Marco Prinz, Niko Kley, Gilles Uzé, Jan Tavernier
Type I Interferon (IFN) is widely used for multiple sclerosis (MS) treatment, but its side effects are limiting and its mechanism of action still unknown. Furthermore, 30-50% of MS patients are unresponsive, and IFN can even induce relapses. Fundamental understanding of the cellular target(s) of IFN will help to optimize treatments by reducing side effects and separating beneficial from detrimental effects. To improve clinical systemic IFN usage, we are developing AcTaferons (Activity-on-Target IFNs = AFNs), optimized IFN-based immunocytokines that allow cell-specific targeting...
November 19, 2018: Journal of Autoimmunity
Taco A van der Meulen, Hermie J M Harmsen, Arnau Vich Vila, Alexander Kurilshikov, Silvia C Liefers, Alexandra Zhernakova, Jingyuan Fu, Cisca Wijmenga, Rinse K Weersma, Karina de Leeuw, Hendrika Bootsma, Fred K L Spijkervet, Arjan Vissink, Frans G M Kroese
OBJECTIVE: Alterations in the microbiota composition of the gastro-intestinal tract are suspected to be involved in the etiopathogenesis of two closely related systemic inflammatory autoimmune diseases: primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE). Our objective was to assess whether alterations in gut and oral microbiota compositions are specific for pSS and SLE. METHODS: 16S ribosomal RNA gene sequencing was performed on fecal samples from 39 pSS patients, 30 SLE patients and 965 individuals from the general population, as well as on buccal swab and oral washing samples from the same pSS and SLE patients...
February 2019: Journal of Autoimmunity
James Broadley, Udaya Seneviratne, Paul Beech, Katherine Buzzard, Helmut Butzkueven, Terence O'Brien, Mastura Monif
OBJECTIVE: To perform a systematic review of the current scientific literature in order to identify variables associated with patient prognosis in autoimmune encephalitis. METHODS: We performed a systematic literature search using MEDLINE, Embase, PubMed and PsychInfo databases. We selected studies that explored the correlation between early clinical and paraclinical findings, and patient outcomes. Data was extracted, analyzed and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines...
January 2019: Journal of Autoimmunity
Stancy Joseph, Nysia I George, Bridgett Green-Knox, Edward L Treadwell, Beverly Word, Sarah Yim, Beverly Lyn-Cook
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 studied...
January 2019: Journal of Autoimmunity
Adrien Mirouse, Lucie Biard, Cloé Comarmond, Marc Lambert, Arsène Mekinian, Yasmina Ferfar, Jean-Emmanuel Kahn, Ygal Benhamou, Laurent Chiche, Fabien Koskas, Philippe Cluzel, Eric Hachulla, Emmanuel Messas, Patrice Cacoub, Tristan Mirault, Matthieu Resche-Rigon, David Saadoun
OBJECTIVE: To report the long term mortality in Takayasu arteritis (TA) and to identify prognosis factors. METHODS: We analyzed the causes of death and the factors associated with mortality in a cohort of 318 patients [median age at diagnosis was 36 [25-47] years and 276 (86%) patients were women] fulfilling American College of Rheumatology and/or Ishikawa criteria of TA. A prognostic score for death and vascular complications was elaborated based on a multivariate model...
January 2019: Journal of Autoimmunity
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