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Journal of Autoimmunity

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https://www.readbyqxmd.com/read/29779929/prescription-medication-use-and-antinuclear-antibodies-in-the-united-states-1999-2004
#1
Gregg E Dinse, Christine G Parks, Helen C S Meier, Caroll A Co, Edward K L Chan, Todd A Jusko, James Yeh, Frederick W Miller
BACKGROUND: Clinical reports link specific medications with the development of antinuclear antibodies (ANA), but population-based evidence is limited. OBJECTIVE: The present study investigated associations between prescription medication use and ANA in a representative sample of the adult noninstitutionalized US population, first focusing on medications previously related to ANA and then considering all medications reported in the National Health and Nutrition Examination Survey (NHANES)...
May 17, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29779928/the-diagnosis-and-clinical-management-of-the-catastrophic-antiphospholipid-syndrome-a-comprehensive-review
#2
REVIEW
Ricard Cervera, Ignasi Rodríguez-Pintó, Gerard Espinosa
The catastrophic antiphospholipid syndrome (CAPS) is a life-threating variant of the antiphospholipid syndrome characterized by the development of multiple thrombosis in a short period of time, usually ending up in the failure of function of several vital organs. Most CAPS episodes are related to a prothrombotic situation or precipitating factor such as infections, surgical procedures or malignant diseases. In patients with CAPS, the development of multiple thrombosis leads to an important cytokine release that worsens the already critical patient's situation...
May 17, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29753567/junctional-adhesion-molecules-jam-b-and-jam-c-promote-autoimmune-mediated-liver-fibrosis-in-mice
#3
Edith Hintermann, Monika Bayer, Clara Benedetta Conti, Sina Fuchs, Michel Fausther, Patrick S Leung, Michel Aurrand-Lions, Richard Taubert, Josef M Pfeilschifter, Mireen Friedrich-Rust, Detlef Schuppan, Jonathan A Dranoff, M Eric Gershwin, Michael P Manns, Beat A Imhof, Urs Christen
Fibrosis remains a serious health concern in patients with chronic liver disease. We recently reported that chemically induced chronic murine liver injury triggers increased expression of junctional adhesion molecules (JAMs) JAM-B and JAM-C by endothelial cells and de novo synthesis of JAM-C by hepatic stellate cells (HSCs). Here, we demonstrate that biopsies of patients suffering from primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) or autoimmune hepatitis (AIH) display elevated levels of JAM-C on portal fibroblasts (PFs), HSCs, endothelial cells and cholangiocytes, whereas smooth muscle cells expressed JAM-C constitutively...
May 9, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29724515/characterization-of-blimp-1-function-in-effector-regulatory-t-cells
#4
Erika Cretney, Patrick Sk Leung, Stephanie Trezise, Dane M Newman, Lucille C Rankin, Charis E Teh, Tracy L Putoczki, Daniel Hd Gray, Gabrielle T Belz, Lisa A Mielke, Sheila Dias, Stephen L Nutt
Regulatory T (Treg ) cells maintain immunological tolerance in steady-state and after immune challenge. Activated Treg cells can undergo further differentiation into an effector state that highly express genes critical for Treg cell function, including ICOS, TIGIT and IL-10, although how this process is controlled is poorly understood. Effector Treg cells also specifically express the transcriptional regulator Blimp-1 whose expression overlaps with many of the canonical markers associated with effector Treg cells, although not all ICOS+ TIGIT+ Treg cells express Blimp-1 or IL-10...
April 30, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29680372/inkt-cells-ameliorate-human-autoimmunity-lessons-from-alopecia-areata
#5
Amal Ghraieb, Aviad Keren, Alex Ginzburg, Yehuda Ullmann, Adam G Schrum, Ralf Paus, Amos Gilhar
Alopecia areata (AA) is understood to be a CD8+/NKG2D+ T cell-dependent autoimmune disease. Here, we demonstrate that human AA pathogenesis of is also affected by iNKT10 cells, an unconventional T cell subtype whose number is significantly increased in AA compared to healthy human skin. AA lesions can be rapidly induced in healthy human scalp skin xenotransplants on Beige-SCID mice by intradermal injections of autologous healthy-donor PBMCs pre-activated with IL-2. We show that in this in vivo model, the development of AA lesions is prevented by recognized the iNKT cell activator, α-galactosylceramide (α-GalCer), which stimulates iNKT cells to expand and produce IL-10...
April 18, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29678346/efficacy-of-tocilizumab-in-takayasu-arteritis-multicenter-retrospective-study-of-46-patients
#6
Arsene Mekinian, Mathieu Resche-Rigon, Cloé Comarmond, Alessandra Soriano, Joel Constans, Laurent Alric, Patrick Jego, Florian Busato, Matthieu Cabon, Robin Dhote, Lazaro Estibaliz, Isabelle Kone Pault, Cédric Landron, Christian Lavigne, Bertrand Lioger, Martin Michaud, Marc Ruivard, Karim Sacre, Jacques Eric Gottenberg, Francis Gaches, Tiphaine Goulenok, Carlo Salvarani, Patrice Cacoub, Olivier Fain, David Saadoun
OBJECTIVES: To assess the efficacy of tocilizumab in patients with Takayasu arteritis (TA). METHODS: We conducted a retrospective multicenter study in 46 TA patients treated with tocilizumab. We analyzed factors associated with response to tocilizumab (assessed using NIH score). RESULTS: Forty-six patients with TA were included, with a median age of 43 years [29-54], and 35 (76%) females. We observed a decrease in the median NIH scale (from 3 [2-3] at baseline to 0 [0-1] and 0 at 3 and 6 months, respectively; p < 0...
April 17, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29673738/tbk1-a-key-regulator-and-potential-treatment-target-for-interferon-positive-sj%C3%A3-gren-s-syndrome-systemic-lupus-erythematosus-and-systemic-sclerosis
#7
Iris L A Bodewes, Erika Huijser, Cornelia G van Helden-Meeuwsen, Liselotte Tas, Ruth Huizinga, Virgil A S H Dalm, P Martin van Hagen, Noortje Groot, Sylvia Kamphuis, Paul L A van Daele, Marjan A Versnel
OBJECTIVE: Upregulation of type I interferons (IFN-I) is a hallmark of systemic autoimmune diseases like primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and systemic sclerosis (SSc). Expression of IFN-I is induced by three different receptor families: Toll-like receptors (TLRs), RIG-like receptors (RLRs) and DNA-sensing receptors (DSRs). TANK-binding kinase (TBK1) is an important signaling hub downstream of RLRs and DSRs. TBK1 activates IRF3 and IRF7, leading to IFN-I production and subsequent induction of interferon stimulated genes (ISGs)...
April 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29636274/the-net-effect-of-combining-rituximab-with-belimumab-in-severe-systemic-lupus-erythematosus
#8
Tineke Kraaij, Sylvia W A Kamerling, Esther N M de Rooij, Paul L A van Daele, Obbo W Bredewold, Jaap A Bakker, Ingeborg M Bajema, Hans U Scherer, Rene E M Toes, Tom J W Huizinga, Ton J Rabelink, Cees van Kooten, Y K Onno Teng
OBJECTIVE: In systemic lupus erythematosus (SLE) patients, excessive formation of neutrophil extracellular traps (NETs) is observed and their degradation is impaired. In vitro, immune complexes (ICx) trigger NET formation while NET-derived DNA is a postulated autoantigen for anti-nuclear autoantibodies (ANAs), found in SLE. Based on these self-perpetuating mechanisms in SLE, this study investigates whether interfering with ICx formation using a combination of rituximab (RTX) and belimumab (BLM) could decrease NET formation and ameliorate disease...
April 7, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29627289/mechanisms-of-neuropsychiatric-lupus-the-relative-roles-of-the-blood-cerebrospinal-fluid-barrier-versus-blood-brain-barrier
#9
Sivan Gelb, Ariel D Stock, Shira Anzi, Chaim Putterman, Ayal Ben-Zvi
The pathogenesis of neuropsychiatric lupus (NPSLE) is believed to include the entry of circulating neuropathic antibodies to the brain via a pathologically permeable blood-brain barrier (BBB). Nevertheless, direct evidence of BBB pathology or mechanisms underlying BBB dysfunction is missing. Here, we examined BBB integrity in an established NPSLE mouse model (MRL/faslpr/lpr ). Surprisingly, challenging the barrier with various exogenous tracers demonstrated insignificant changes in BBB permeability. Furthermore, electron microscopy showed no ultrastructure changes supporting hyper-permeability...
April 4, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29610014/gain-of-function-mutation-and-inflammasome-driven-diseases-in-human-and-mouse-models
#10
REVIEW
Mario D Cordero, Elísabet Alcocer-Gómez, Bernhard Ryffel
Activation of the NLRP3 inflammasome, a multiprotein complex, leading to caspase activation with production of proinflammatory IL-1β represents a major pathway of inflammation. Recent, studies in mice and human patients uncovered several gain-of- function (GOF) mutations in inflammasome sensor proteins that allow inflammasome assembly in the absence of cognate ligands to trigger autoinflammatory syndromes. Cryopyrin-associated periodic syndromes (CAPS) are rare autoinflammatory diseases, comprising a broad disease spectrum with varying severity...
March 30, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29576246/autoantibodies-targeting-tlr-and-smad-pathways-define-new-subgroups-in-systemic-lupus-erythematosus
#11
Myles J Lewis, Michael B McAndrew, Colin Wheeler, Nicholas Workman, Pooja Agashe, Jens Koopmann, Ezam Uddin, David L Morris, Lu Zou, Richard Stark, John Anson, Andrew P Cope, Timothy J Vyse
OBJECTIVES: The molecular targets of the vast majority of autoantibodies in systemic lupus erythematosus (SLE) are unknown. We set out to identify novel autoantibodies in SLE to improve diagnosis and identify subgroups of SLE individuals. METHODS: A baculovirus-insect cell expression system was used to create an advanced protein microarray with 1543 full-length human proteins expressed with a biotin carboxyl carrier protein (BCCP) folding tag, to enrich for correctly folded proteins...
March 22, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29551295/systemic-activation-of-nlrp3-inflammasome-in-patients-with-severe-primary-sj%C3%A3-gren-s-syndrome-fueled-by-inflammagenic-dna-accumulations
#12
Aigli G Vakrakou, Sorina Boiu, Panayiotis D Ziakas, Evangelia Xingi, Haralabia Boleti, Menelaos N Manoussakis
Sjögren's syndrome (SS) patients manifest high cell-free DNA (cf-DNA) levels in serum, associated with impaired DNaseI activity. Undegraded DNA may accumulate in tissues and act as an inflammasome-activating signal. Herein, we investigated the occurrence of aberrant DNA build-up in various biologic compartments of SS patients and its correlation with the activity of NLRP3 and AIM2 inflammasomes. For this purpose, we evaluated sera, PBMC, circulating monocytes and salivary glands (SG) from different SS patient subgroups and controls...
March 16, 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29525183/line1-contributes-to-autoimmunity-through-both-rig-i-and-mda5-mediated-rna-sensing-pathways
#13
Ke Zhao, Juan Du, Yanfeng Peng, Peng Li, Shaohua Wang, Yu Wang, Jingwei Hou, Jian Kang, Wenwen Zheng, Shucheng Hua, Xiao-Fang Yu
Improper host immune activation leads to the development of the autoimmune disease Aicardi-Goutières syndrome (AGS), which is attributed to defined genetic mutations in such proteins as TREX1 and ADAR1. The mechanism of immune activation in AGS patients has not been thoroughly elucidated to date. In this study, we report that endogenous LINE1 components trigger IFNβ production in multiple human cell types, including those defective for cGAS/STING-mediated DNA sensing. In these cells, LINE1 DNA synthesis and retrotransposition were not required for LINE1-triggered immune activation, but RNA sensing pathways were essential...
June 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29503043/origins-and-specificity-of-auto-antibodies-in-sm-sle-patients
#14
Olga Kalinina, Yoram Louzoun, Yue Wang, Tammy Utset, Martin Weigert
Systemic lupus erythematosus (SLE) is a complex autoimmune disease accompanied by production of autoantibodies directed to a variety of self-proteins and nucleic acids. The genetic basis of SLE is also complex with at least 40 susceptibility loci identified. This complexity suggests that there are a variety of SLE manifestations; nevertheless, SLE is treated as a single disease clinically. One unique SLE target is the Smith antigen (Sm), a nuclear ribonucleoprotein complex. Sm response occurs in 25% of patients with SLE...
June 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29503042/engrafting-human-regulatory-t-cells-with-a-flexible-modular-chimeric-antigen-receptor-technology
#15
Stefanie Koristka, Alexandra Kegler, Ralf Bergmann, Claudia Arndt, Anja Feldmann, Susann Albert, Marc Cartellieri, Armin Ehninger, Gerhard Ehninger, Jan Moritz Middeke, Martin Bornhäuser, Marc Schmitz, Jens Pietzsch, Katja Akgün, Tjalf Ziemssen, Jörg Steinbach, Michael P Bachmann
As regulatory T cells (Tregs) play a fundamental role in immune homeostasis their adoptive transfer emerged as a promising treatment strategy for inflammation-related diseases. Preclinical animal models underline the superiority of antigen-specific Tregs compared to polyclonal cells. Here, we applied a modular chimeric antigen receptor (CAR) technology called UniCAR for generation of antigen-specific human Tregs. In contrast to conventional CARs, UniCAR-endowed Tregs are indirectly linked to their target cells via a separate targeting module (TM)...
June 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29486915/rescue-of-autophagy-and-lysosome-defects-in-salivary-glands-of-mrl-lpr-mice-by-a-therapeutic-phosphopeptide
#16
Baihui Li, Fengjuan Wang, Nicolas Schall, Sylviane Muller
Sjögren's syndrome is a multifactorial systemic autoimmune disorder characterized by lymphocytic infiltrates in exocrine organs. Patients present with sicca symptoms, such as extensive dry eyes and dry mouth, and parotid enlargement. Other serious complications include profound fatigue, chronic pain, major organ involvement, neuropathies and lymphomas. Current treatments only focus on relieving symptoms and do not target the origin of the disease, which is largely unknown. The question we addressed here was whether some defects exist in autophagy processes in Sjögren's syndrome and if they can be corrected or minimized using an appropriate mechanism-driven treatment targeting this central survival pathway...
June 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29371048/serum-microrna-screening-and-functional-studies-reveal-mir-483-5p-as-a-potential-driver-of-fibrosis-in-systemic-sclerosis
#17
Eleni Chouri, Nila H Servaas, Cornelis P J Bekker, Alsya J Affandi, Marta Cossu, Maarten R Hillen, Chiara Angiolilli, Jorre S Mertens, Lucas L van den Hoogen, Sandra Silva-Cardoso, Maarten van der Kroef, Nadia Vazirpanah, Catharina G K Wichers, Tiago Carvalheiro, Sofie L M Blokland, Barbara Giovannone, Laura Porretti, Wioleta Marut, Barbara Vigone, Joel A G van Roon, Lorenzo Beretta, Marzia Rossato, Timothy R D J Radstake
OBJECTIVE: MicroRNAs (miRNAs) are regulatory molecules, which have been addressed as potential biomarkers and therapeutic targets in rheumatic diseases. Here, we investigated the miRNA signature in the serum of systemic sclerosis (SSc) patients and we further assessed their expression in early stages of the disease. METHODS: The levels of 758 miRNAs were evaluated in the serum of 26 SSc patients as compared to 9 healthy controls by using an Openarray platform. Three miRNAs were examined in an additional cohort of 107 SSc patients and 24 healthy donors by single qPCR...
May 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29366602/treg-specific-deletion-of-nkap-results-in-severe-systemic-autoimmunity-due-to-peripheral-loss-of-tregs
#18
Barsha Dash, Michael J Shapiro, Ji Young Chung, Sinibaldo Romero Arocha, Virginia Smith Shapiro
Regulatory T cells are critical for the generation and maintenance of peripheral tolerance. Conditional deletion of the transcriptional repressor NKAP in Tregs using Foxp3-YFP-cre NKAP conditional knockout mice causes aggressive autoimmunity characterized by thymic atrophy, lymphadenopathy, peripheral T cell activation, generation of autoantibodies, immune infiltration into several organs, and crusty skin at 3 weeks of age, similar to that of "scurfy" Foxp3-mutant mice. While Treg development in the thymus proceeds normally in the absence of NKAP, there is a severe loss of thymically-derived Tregs in the periphery...
May 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29352633/current-concerns-and-perspectives-on-zika-virus-co-infection-with-arboviruses-and-hiv
#19
REVIEW
Hussin A Rothan, Mehdi R M Bidokhti, Siddappa N Byrareddy
Dissemination of vector-borne viruses, such as Zika virus (ZIKV), in tropical and sub-tropical regions has a complicated impact on the immunopathogenesis of other endemic viruses such as dengue virus (DENV), chikungunya virus (CHIKV) and human immunodeficiency virus (HIV). The consequences of the possible co-infections with these viruses have specifically shown significant impact on the treatment and vaccination strategies. ZIKV is a mosquito-borne flavivirus from African and Asian lineages that causes neurological complications in infected humans...
May 2018: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29183642/tick-borne-diseases-and-autoimmunity-a-comprehensive-review
#20
REVIEW
Yhojan Rodríguez, Manuel Rojas, M Eric Gershwin, Juan-Manuel Anaya
Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick infestation...
March 2018: Journal of Autoimmunity
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