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

TRIF deficiency protects non-obese diabetic mice from type 1 diabetes by modulating the gut microbiota and dendritic cells.
n L Abstract The incidence of type 1 diabetes (T1D) is determined by both genetic and environmental factors. In recent years, the gut microbiota have been identified to be an important environmental factor that could modify diabetes susceptibility. We have previously shown that Myeloid differentiation primary response gene 88 (MyD88), a major adaptor protein downstream of most innate immune Toll-like receptor (TLR) signaling, is important for mediating diabetes susceptibility in the non-obese diabetic (NOD) mouse model of human T1D. Here we report the role of TIR-domain-containing adapter-inducing interferon-&beta...
Source: Journal of Autoimmunity - June 27, 2018 Category: Allergy & Immunology Authors: Gülden E, Chao C, Tai N, Pearson JA, Peng J, Majewska-Szczepanik M, Zhou Z, Wong FS, Wen L Tags: J Autoimmun Source Type: research

Protective role of commensal bacteria in Sj ögren Syndrome.
Protective role of commensal bacteria in Sjögren Syndrome. J Autoimmun. 2018 Jun 19;: Authors: Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, Simmons KT, Schady D, Swennes AG, Pflugfelder SC, Britton RA, de Paiva CS Abstract CD25 knock-out (CD25KO) mice spontaneously develop Sjögren Syndrome (SS)-like inflammation. We investigated the role of commensal bacteria by comparing CD25KO mice housed in conventional or germ-free conditions. Germ-free CD25KO mice have greater corneal barrier dysfunction, lower goblet cell density, increased total lymphocytic infiltration score, increased e...
Source: Journal of Autoimmunity - June 19, 2018 Category: Allergy & Immunology Authors: Zaheer M, Wang C, Bian F, Yu Z, Hernandez H, de Souza RG, Simmons KT, Schady D, Swennes AG, Pflugfelder SC, Britton RA, de Paiva CS Tags: J Autoimmun Source Type: research

Hematopoietic stem cell therapy for autoimmune diseases - Clinical experience and mechanisms.
Abstract With accumulating evidence and improved outcomes along with recognition that modern biological therapies are not universally effective, require chronic administration and have high acquisition costs, hematopoietic stem cell transplantation (HSCT) has become an emerging direction for cell therapy in autoimmune diseases (ADs). The goal of this therapy is to induce medication-free remissions by resetting the immune system into a naïve and self-tolerant state through eradication of the autoreactive immunologic memory and profound re-configuration of the immune system induced by the transplant procedure. ...
Source: Journal of Autoimmunity - June 19, 2018 Category: Allergy & Immunology Authors: Alexander T, Farge D, Badoglio M, Lindsay JO, Muraro PA, Snowden JA, Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT) Tags: J Autoimmun Source Type: research

Modulation of human Th17 cell responses through complement receptor 3 (CD11  b/CD18) ligation on monocyte-derived dendritic cells.
CONCLUSION: Overall, our findings underline the potential of targeted CD11b ligation on human dendritic cells for the engineering of suppressive immunotherapy for Th17-related autoimmune disorders. PMID: 29908907 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 13, 2018 Category: Allergy & Immunology Authors: Nowatzky J, Manches O, Khan SA, Godefroy E, Bhardwaj N Tags: J Autoimmun Source Type: research

Targeted inhibition of Axl receptor tyrosine kinase ameliorates anti-GBM-induced lupus-like nephritis.
Abstract Glomerulonephritis (GN) is a typical lesion in autoantibody and immune complex disorders, including SLE. Because the Gas6/Axl pathway has been implicated in the pathogenesis of many types of GN, targeting this pathway might ameliorate GN. Consequently, we have studied the efficacy and mechanism of R428, a potent selective Axl inhibitor, in the prevention of experimental anti-GBM nephritis. Axl upregulation was investigated with Sp1/3 siRNA in the SV40-transformed mesangial cells. For Axl inhibition, a daily dose of R428 (125 mg/kg) or vehicle was administered orally. GN was induced with anti-GBM sera. R...
Source: Journal of Autoimmunity - June 9, 2018 Category: Allergy & Immunology Authors: Zhen Y, Lee IJ, Finkelman FD, Shao WH Tags: J Autoimmun Source Type: research

11 Beta-hydroxysteroid dehydrogenase type 1 regulates synovitis, joint destruction, and systemic bone loss in chronic polyarthritis.
CONCLUSIONS: We demonstrate a fundamental role for 11β-HSD1 in the suppression of synovitis, joint destruction, and systemic bone loss. Whilst a role for 11β-HSD1 inhibitors has been proposed for metabolic complications in inflammatory diseases, our study suggests that this approach would greatly exacerbate disease severity. PMID: 29891135 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 8, 2018 Category: Allergy & Immunology Authors: Hardy RS, Fenton C, Croft AP, Naylor AJ, Begum R, Desanti G, Buckley CD, Lavery G, Cooper MS, Raza K Tags: J Autoimmun Source Type: research

An autophagy-targeting peptide to treat chronic inflammatory demyelinating polyneuropathies.
ler S Abstract Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disease of the peripheral nerves evolving with diffuse sensory and motor symptoms. Although it is claimed that in neurodegenerative pathologies, a common feature is the failure of proteolytic systems to adequately eliminate aggregated or misfolded proteins, it has not been addressed whether autophagy, a central "clearance" system delivering damaged intracellular components to lysosomes, is affected in CIDP. The focus of the present investigation was therefore to determine if some defects exist in autophagy pr...
Source: Journal of Autoimmunity - June 5, 2018 Category: Allergy & Immunology Authors: Brun S, Schall N, Bonam SR, Bigaut K, Mensah-Nyagan AG, de Sèze J, Muller S Tags: J Autoimmun Source Type: research

Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.
Abstract Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transform...
Source: Journal of Autoimmunity - May 31, 2018 Category: Allergy & Immunology Authors: Rizzetto L, Fava F, Tuohy KM, Selmi C Tags: J Autoimmun Source Type: research

B-cell activating factor and related genetic variants in lupus related atherosclerosis.
CONCLUSIONS: High BAFF serum levels in the upper 4th quartile as well as BAFF genetic variants seem to increase susceptibility for both lupus and lupus related subclinical atherosclerosis implying B-cell hyperactivity as a potential contributor in the pronounced lupus related atherosclerotic risk. PMID: 29859654 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 30, 2018 Category: Allergy & Immunology Authors: Theodorou E, Nezos A, Antypa E, Ioakeimidis D, Koutsilieris M, Tektonidou M, Moutsopoulos HM, Mavragani CP Tags: J Autoimmun Source Type: research

Engineered MBP-specific human Tregs ameliorate MOG-induced EAE through IL-2-triggered inhibition of effector T cells.
Abstract Expanded polyclonal T regulatory cells (Tregs) offer great promise for the treatment of immune-mediated diseases. Inhibition by Tregs is under the control of the T-cell receptor (TCR). Therefore, we created Tregs with defined antigen specificity, using a recombinant T-cell receptor isolated from a myelin-basic protein specific T-cell clone of a multiple sclerosis (MS) patient (Ob2F3). We expressed this TCR using a retroviral expression vector in human Tregs from peripheral blood. We observed that transduced Tregs were activated in vitro in response to myelin basic protein (MBP) peptide on DR15 antigen-pre...
Source: Journal of Autoimmunity - May 29, 2018 Category: Allergy & Immunology Authors: Kim YC, Zhang AH, Yoon J, Culp WE, Lees JR, Wucherpfennig KW, Scott DW Tags: J Autoimmun Source Type: research

Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint.
Memory T cells specific to citrullinated α-enolase are enriched in the rheumatic joint. J Autoimmun. 2018 May 28;: Authors: Pieper J, Dubnovitsky A, Gerstner C, James EA, Rieck M, Kozhukh G, Tandre K, Pellegrino S, Gebe JA, Rönnblom L, Sandalova T, Kwok WW, Klareskog L, Buckner JH, Achour A, Malmström V Abstract ACPA-positive rheumatoid arthritis (RA) is associated with distinct HLA-DR alleles and immune responses to many citrullinated self-antigens. Herein we investigated the T cell epitope confined within α-enolase326-340 in the context of HLA-DRB1*04:01 and assessed the corres...
Source: Journal of Autoimmunity - May 28, 2018 Category: Allergy & Immunology Authors: Pieper J, Dubnovitsky A, Gerstner C, James EA, Rieck M, Kozhukh G, Tandre K, Pellegrino S, Gebe JA, Rönnblom L, Sandalova T, Kwok WW, Klareskog L, Buckner JH, Achour A, Malmström V Tags: J Autoimmun Source Type: research

Condensin Smc4 promotes inflammatory innate immune response by epigenetically enhancing NEMO transcription.
Abstract Structural maintenance of chromosome (Smc) protein complex (condensin) plays a central role in organizing and compacting chromosomes, which determines DNA-binding activity and gene expression; however, the role of condensin Smc in innate immunity and inflammation remains largely unknown. Through a high-throughput screening of the epigenetic modifiers, we identified Smc4, a core subunit of condensin, to potentially promote inflammatory innate immune response. Knockdown or deficiency of Smc4 inhibited TLR- or virus-triggered production of proinflammatory cytokines IL-6, TNF-α and IFN-β in macroph...
Source: Journal of Autoimmunity - May 24, 2018 Category: Allergy & Immunology Authors: Wang Q, Wang C, Li N, Liu X, Ren W, Wang Q, Cao X Tags: J Autoimmun Source Type: research

The diagnosis and clinical management of the catastrophic antiphospholipid syndrome: A comprehensive review.
Espinosa G Abstract 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. The disease usually involves the ...
Source: Journal of Autoimmunity - May 17, 2018 Category: Allergy & Immunology Authors: Cervera R, Rodríguez-Pintó I, Espinosa G Tags: J Autoimmun Source Type: research

Prescription medication use and antinuclear antibodies in the United States, 1999-2004.
CONCLUSIONS: Our findings in the general population do not confirm most clinically reported positive associations between specific medications and ANA in some individuals. However, novel positive ANA associations with other medications, as well as unexplained inverse associations with certain classes of medications and overall medication use, deserve further research to clarify the possible roles of medications as risk and protective factors in the development of autoantibodies and autoimmune disease. PMID: 29779929 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 17, 2018 Category: Allergy & Immunology Authors: Dinse GE, Parks CG, Meier HCS, Co CA, Chan EKL, Jusko TA, Yeh J, Miller FW Tags: J Autoimmun Source Type: research

Junctional adhesion molecules JAM-B and JAM-C promote autoimmune-mediated liver fibrosis in mice.
Abstract 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 ...
Source: Journal of Autoimmunity - May 9, 2018 Category: Allergy & Immunology Authors: Hintermann E, Bayer M, Conti CB, Fuchs S, Fausther M, Leung PS, Aurrand-Lions M, Taubert R, Pfeilschifter JM, Friedrich-Rust M, Schuppan D, Dranoff JA, Gershwin ME, Manns MP, Imhof BA, Christen U Tags: J Autoimmun Source Type: research

Characterization of Blimp-1 function in effector regulatory T cells.
In this study, we addressed the role of Blimp-1 in effector Treg cell function. Mice lacking Blimp-1 specifically in Treg cells mature normally, but succumb to a multi-organ inflammatory disease later in life. Blimp-1 is not required for Treg cell differentiation, with mutant mice having increased numbers of effector Treg cells, but regulated a suite of genes involved in cell signaling, communication and survival, as well as being essential for the expression of the immune modulatory cytokine IL-10. Thus, Blimp-1 is a marker of effector Treg cells in all contexts examined and is required for the full functionality of these...
Source: Journal of Autoimmunity - April 30, 2018 Category: Allergy & Immunology Authors: Cretney E, Leung PS, Trezise S, Newman DM, Rankin LC, Teh CE, Putoczki TL, Gray DH, Belz GT, Mielke LA, Dias S, Nutt SL Tags: J Autoimmun Source Type: research

iNKT cells ameliorate human autoimmunity: Lessons from alopecia areata.
Abstract 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-g...
Source: Journal of Autoimmunity - April 18, 2018 Category: Allergy & Immunology Authors: Ghraieb A, Keren A, Ginzburg A, Ullmann Y, Schrum AG, Paus R, Gilhar A Tags: J Autoimmun Source Type: research

Efficacy of tocilizumab in Takayasu arteritis: Multicenter retrospective study of 46 patients.
ain O, Saadoun D, French Takayasu network Abstract 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 
Source: Journal of Autoimmunity - April 17, 2018 Category: Allergy & Immunology Authors: Mekinian A, Resche-Rigon M, Comarmond C, Soriano A, Constans J, Alric L, Jego P, Busato F, Cabon M, Dhote R, Estibaliz L, Pault IK, Landron C, Lavigne C, Lioger B, Michaud M, Ruivard M, Sacre K, Gottenberg JE, Gaches F, Goulenok T, Salvarani C, Cacoub P, Tags: J Autoimmun Source Type: research

TBK1: A key regulator and potential treatment target for interferon positive Sj ögren's syndrome, systemic lupus erythematosus and systemic sclerosis.
CONCLUSIONS: TBK1 inhibition reduced expression of ISGs in PBMCs from IFNpos patients with systemic autoimmune diseases indicating TBK1 as a potential treatment target. PMID: 29673738 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 16, 2018 Category: Allergy & Immunology Authors: Bodewes ILA, Huijser E, van Helden-Meeuwsen CG, Tas L, Huizinga R, Dalm VASH, van Hagen PM, Groot N, Kamphuis S, van Daele PLA, Versnel MA Tags: J Autoimmun Source Type: research

The NET-effect of combining rituximab with belimumab in severe systemic lupus erythematosus.
CONCLUSIONS: This study provides novel insights into clinical beneficence of reducing excessive NET formation in SLE by therapeutic targeting ANA production with RTX + BLM. Altogether putting forward a new treatment concept that specifically ameliorates underlying SLE pathophysiology. TRIAL REGISTRATION: ClinicalTrials.gov NCT02284984. PMID: 29636274 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 7, 2018 Category: Allergy & Immunology Authors: Kraaij T, Kamerling SWA, de Rooij ENM, van Daele PLA, Bredewold OW, Bakker JA, Bajema IM, Scherer HU, Toes REM, Huizinga TJW, Rabelink TJ, van Kooten C, Teng YKO Tags: J Autoimmun Source Type: research

Mechanisms of neuropsychiatric lupus: The relative roles of the blood-cerebrospinal fluid barrier versus blood-brain barrier.
Abstract 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. However, we...
Source: Journal of Autoimmunity - April 4, 2018 Category: Allergy & Immunology Authors: Gelb S, Stock AD, Anzi S, Putterman C, Ben-Zvi A Tags: J Autoimmun Source Type: research

Gain of function mutation and inflammasome driven diseases in human and mouse models.
fel B Abstract 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. CAPS are associated with GOF mutations in the NLR...
Source: Journal of Autoimmunity - March 30, 2018 Category: Allergy & Immunology Authors: Cordero MD, Alcocer-Gómez E, Ryffel B Tags: J Autoimmun Source Type: research

Autoantibodies targeting TLR and SMAD pathways define new subgroups in systemic lupus erythematosus.
Abstract 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. Sera from a discovery cohort of UK and US SLE individuals (n = 186) and age/ethnicity matched controls (n = 18...
Source: Journal of Autoimmunity - March 22, 2018 Category: Allergy & Immunology Authors: Lewis MJ, McAndrew MB, Wheeler C, Workman N, Agashe P, Koopmann J, Uddin E, Morris DL, Zou L, Stark R, Anson J, Cope AP, Vyse TJ Tags: J Autoimmun Source Type: research

Systemic activation of NLRP3 inflammasome in patients with severe primary Sj ögren's syndrome fueled by inflammagenic DNA accumulations.
Systemic activation of NLRP3 inflammasome in patients with severe primary Sjögren's syndrome fueled by inflammagenic DNA accumulations. J Autoimmun. 2018 Mar 15;: Authors: Vakrakou AG, Boiu S, Ziakas PD, Xingi E, Boleti H, Manoussakis MN Abstract 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 wit...
Source: Journal of Autoimmunity - March 15, 2018 Category: Allergy & Immunology Authors: Vakrakou AG, Boiu S, Ziakas PD, Xingi E, Boleti H, Manoussakis MN Tags: J Autoimmun Source Type: research

LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways.
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. LINE1-triggered immune activation could be suppressed by diverse LINE1 inhibitors, including AGS-associated proteins targeting LINE1 RNA or proteins. However, AGS-associated ADAR1 or TREX1 mutants were defective in suppressing LINE1 retrotransposition or LINE1-triggered immune activation. The...
Source: Journal of Autoimmunity - March 7, 2018 Category: Allergy & Immunology Authors: Zhao K, Du J, Peng Y, Li P, Wang S, Wang Y, Hou J, Kang J, Zheng W, Hua S, Yu XF Tags: J Autoimmun Source Type: research

Engrafting human regulatory T cells with a flexible modular chimeric antigen receptor technology.
mann MP Abstract 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). Thus, transduced Tregs can be applied universally ...
Source: Journal of Autoimmunity - March 1, 2018 Category: Allergy & Immunology Authors: Koristka S, Kegler A, Bergmann R, Arndt C, Feldmann A, Albert S, Cartellieri M, Ehninger A, Ehninger G, Middeke JM, Bornhäuser M, Schmitz M, Pietzsch J, Akgün K, Ziemssen T, Steinbach J, Bachmann MP Tags: J Autoimmun Source Type: research

Origins and specificity of auto-antibodies in Sm+ SLE patients.
Abstract 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. To simplify analysis of the disease and its associated autoantibody repertoire, we fo...
Source: Journal of Autoimmunity - March 1, 2018 Category: Allergy & Immunology Authors: Kalinina O, Louzoun Y, Wang Y, Utset T, Weigert M Tags: J Autoimmun Source Type: research

Rescue of autophagy and lysosome defects in salivary glands of MRL/lpr mice by a therapeutic phosphopeptide.
Abstract 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 b...
Source: Journal of Autoimmunity - February 24, 2018 Category: Allergy & Immunology Authors: Li B, Wang F, Schall N, Muller S Tags: J Autoimmun Source Type: research

Targeting CD6 for the treatment of experimental autoimmune uveitis.
CONCLUSIONS: Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases. PMID: 29472120 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - February 19, 2018 Category: Allergy & Immunology Authors: Zhang L, Li Y, Qiu W, Bell BA, Dvorina N, Baldwin WM, Singer N, Kern T, Caspi RR, Fox DA, Lin F Tags: J Autoimmun Source Type: research

Beyond thrombosis: Anti- β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome.
Beyond thrombosis: Anti-β2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome. J Autoimmun. 2018 Feb 14;: Authors: Chighizola CB, Pregnolato F, Andreoli L, Bodio C, Cesana L, Comerio C, Gerosa M, Grossi C, Kumar R, Lazzaroni MG, Mahler M, Mattia E, Nalli C, Norman GL, Raimondo MG, Ruffatti A, Tonello M, Trespidi L, Tincani A, Borghi MO, Meroni PL Abstract Antibodies against β2 glycoprotein I (anti-β2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and confo...
Source: Journal of Autoimmunity - February 14, 2018 Category: Allergy & Immunology Authors: Chighizola CB, Pregnolato F, Andreoli L, Bodio C, Cesana L, Comerio C, Gerosa M, Grossi C, Kumar R, Lazzaroni MG, Mahler M, Mattia E, Nalli C, Norman GL, Raimondo MG, Ruffatti A, Tonello M, Trespidi L, Tincani A, Borghi MO, Meroni PL Tags: J Autoimmun Source Type: research

The treatment of anti-phospholipid syndrome: A comprehensive clinical approach.
Abstract Anti-phospholipid syndrome (APS) is an acquired pro-thrombotic autoimmune disease that predisposes to thrombotic events and/or obstetric complications, in the persistent presence of anti-phospholipid antibodies (aPL). Life long moderate-intensity anticoagulation is the option of choice for aPL-positive patients with a previous thrombosis; critical issues concern the management of those with a history of arterial event due to the high rate of recurrence. Alternatives comprise anti-platelet agents and high-intensity anticoagulation. Low dose aspirin (LDASA) and low molecular weight heparin provide the mains...
Source: Journal of Autoimmunity - February 12, 2018 Category: Allergy & Immunology Authors: Chighizola CB, Andreoli L, Gerosa M, Tincani A, Ruffatti A, Meroni PL Tags: J Autoimmun Source Type: research

Low CD25 on autoreactive Tregs impairs tolerance via low dose IL-2 and antigen delivery.
Abstract Dendritic cell (DC)-mediated T cell tolerance deficiencies contribute to the pathogenesis of autoimmune diseases such as type 1 diabetes. Delivering self-antigen to dendritic-cell inhibitory receptor-2 (DCIR2)+ DCs can delay but not completely block diabetes development in NOD mice. These DCIR2-targeting antibodies induce tolerance via deletion and anergy, but do not increase islet-specific Tregs. Because low-dose IL-2 (LD-IL-2) administration can preferentially expand Tregs, we tested whether delivering islet-antigen to tolerogenic DCIR2+ DCs along with LD-IL-2 would boost islet-specific Tregs and furthe...
Source: Journal of Autoimmunity - February 10, 2018 Category: Allergy & Immunology Authors: Hotta-Iwamura C, Benck C, Coley WD, Liu Y, Zhao Y, Quiel JA, Tarbell KV Tags: J Autoimmun Source Type: research

The immunobiology of mucosal-associated invariant T cell (MAIT) function in primary biliary cholangitis: Regulation by cholic acid-induced Interleukin-7.
Abstract Mucosal-associated invariant T (MAIT) cells are novel innate-like T cells constituting a significant proportion of circulating and hepatic T cells. Herein, we extensively examine the phenotypical and functional alterations of MAIT cells and their regulation in a cohort of 56 patients with Primary Biliary Cholangitis (PBC) and 53 healthy controls (HC). Additionally alterations of MAIT cells were assessed before and after UDCA treatment. Finally the localization of MAIT cell in liver was examined using specific tetramer staining and the underlying mechanisms of these alterations in PBC were explored. Our da...
Source: Journal of Autoimmunity - February 8, 2018 Category: Allergy & Immunology Authors: Jiang X, Lian M, Li Y, Zhang W, Wang Q, Wei Y, Zhang J, Chen W, Xiao X, Miao Q, Bian Z, Qiu D, Fang J, Ansari AA, Leung PSC, Coppel RL, Tang R, Gershwin ME, Ma X Tags: J Autoimmun Source Type: research

TGF- β signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis.
TGF-β signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis. J Autoimmun. 2018 Feb 06;: Authors: Peres RS, Donate PB, Talbot J, Cecilio NT, Lobo PR, Machado CC, Lima KWA, Oliveira RD, Carregaro V, Nakaya HI, Cunha TM, Alves-Filho JC, Liew FY, Louzada-Junior P, Cunha FQ Abstract Rheumatoid arthritis (RA) is an autoimmune arthropathy characterized by chronic articular inflammation. Methotrexate (MTX) remains the first-line therapy for RA and its anti-inflammatory effect is associated with the maintenance of high levels of extrac...
Source: Journal of Autoimmunity - February 6, 2018 Category: Allergy & Immunology Authors: Peres RS, Donate PB, Talbot J, Cecilio NT, Lobo PR, Machado CC, Lima KWA, Oliveira RD, Carregaro V, Nakaya HI, Cunha TM, Alves-Filho JC, Liew FY, Louzada-Junior P, Cunha FQ Tags: J Autoimmun Source Type: research

T cells are influenced by a long non-coding RNA in the autoimmune associated PTPN2 locus.
Padyukov L Abstract Non-coding SNPs in the protein tyrosine phosphatase non-receptor type 2 (PTPN2) locus have been linked with several autoimmune diseases, including rheumatoid arthritis, type I diabetes, and inflammatory bowel disease. However, the functional consequences of these SNPs are poorly characterized. Herein, we show in blood cells that SNPs in the PTPN2 locus are highly correlated with DNA methylation levels at four CpG sites downstream of PTPN2 and expression levels of the long non-coding RNA (lncRNA) LINC01882 downstream of these CpG sites. We observed that LINC01882 is mainly expressed in T cells ...
Source: Journal of Autoimmunity - February 2, 2018 Category: Allergy & Immunology Authors: Houtman M, Shchetynsky K, Chemin K, Hensvold AH, Ramsköld D, Tandre K, Eloranta ML, Rönnblom L, Uebe S, Catrina AI, Malmström V, Padyukov L Tags: J Autoimmun Source Type: research

Predicting progression to diabetes in islet autoantibody positive children.
The objective of this study was to explore less costly and less time-consuming options. All children being prospectively followed by the Diabetes Autoimmunity Study in the Young (DAISY) who had a complete baseline OGTT and at least one confirmed islet autoantibody (Ab+) were included in this study (n = 68). Of 68 Ab+ subjects with a baseline OGTT, 25 developed diabetes after a mean follow-up 5.7 yrs, at a mean age of 12.4 yrs. Univariate proportional hazards (PH) models suggested that age at seroconversion, number of Ab+, IA-2A levels, HbA1c and metabolic variables from the OGTT predicted progressi...
Source: Journal of Autoimmunity - January 27, 2018 Category: Allergy & Immunology Authors: Steck AK, Dong F, Frohnert BI, Waugh K, Hoffman M, Norris JM, Rewers MJ Tags: J Autoimmun Source Type: research

Th17  cells, γδ T cells and their interplay in EAE and multiple sclerosis.
Th17 cells, γδ T cells and their interplay in EAE and multiple sclerosis. J Autoimmun. 2018 Jan 21;: Authors: McGinley AM, Edwards SC, Raverdeau M, Mills KHG Abstract Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis (MS) that shares many features with the human disease. This review will focus on the role of IL-17-secreting CD4 and γδ T cells in EAE and MS, the plasticity of Th17 cells in vivo and the application of these findings to the understating of the pathogenesis and the development of new treatments for MS. There is convin...
Source: Journal of Autoimmunity - January 21, 2018 Category: Allergy & Immunology Authors: McGinley AM, Edwards SC, Raverdeau M, Mills KHG Tags: J Autoimmun Source Type: research

Treg-specific deletion of NKAP results in severe, systemic autoimmunity due to peripheral loss of Tregs.
Abstract 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 Tre...
Source: Journal of Autoimmunity - January 20, 2018 Category: Allergy & Immunology Authors: Dash B, Shapiro MJ, Chung JY, Romero Arocha S, Shapiro VS Tags: J Autoimmun Source Type: research

Current concerns and perspectives on Zika virus co-infection with arboviruses and HIV.
Abstract 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. Many of DENV and CHIKV endemic regions have been experien...
Source: Journal of Autoimmunity - January 16, 2018 Category: Allergy & Immunology Authors: Rothan HA, Bidokhti MRM, Byrareddy SN Tags: J Autoimmun Source Type: research

Expression level of risk genes of MHC class II is a susceptibility factor for autoimmunity: New insights.
Abstract To date, the study of the impact of major hystocompatibility complex on autoimmunity has been prevalently focused on structural diversity of MHC molecules in binding and presentation of (auto)antigens to cognate T cells. Recently, a number of experimental evidences suggested new points of view to investigate the complex relationships between MHC gene expression and the individual predisposition to autoimmune diseases. Irrespective of the nature of the antigen, a threshold of MHC-peptide complexes needs to be reached, as well as a threshold of T cell receptors engaged is required, for the activation and pr...
Source: Journal of Autoimmunity - January 10, 2018 Category: Allergy & Immunology Authors: Gianfran C, Pisapia L, Picascia S, Strazzullo M, Del Pozzo G Tags: J Autoimmun Source Type: research

Th17-lineage cells in pulmonary sarcoidosis and L öfgren's syndrome: Friend or foe?
Th17-lineage cells in pulmonary sarcoidosis and Löfgren's syndrome: Friend or foe? J Autoimmun. 2018 Jan 05;: Authors: Miedema JR, Kaiser Y, Broos CE, Wijsenbeek MS, Grunewald J, Kool M Abstract Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressiv...
Source: Journal of Autoimmunity - January 5, 2018 Category: Allergy & Immunology Authors: Miedema JR, Kaiser Y, Broos CE, Wijsenbeek MS, Grunewald J, Kool M Tags: J Autoimmun Source Type: research

Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort.
In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip. Cox proportional hazards analyses were performed to discover the SNPs associated with the risk for IA, T1D, or both. Three regions were associated with the risk of developing any persistent confirmed islet autoantibody: one known region near SH2B3 (HR = 1.35, p = 3.58 × 10-7) with Bonferroni-corrected significance and another known region near PTPN22 (HR = 1.46, p = 2.17 × 10-6) and one n...
Source: Journal of Autoimmunity - January 5, 2018 Category: Allergy & Immunology Authors: Sharma A, Liu X, Hadley D, Hagopian W, Chen WM, Onengut-Gumuscu S, Törn C, Steck AK, Frohnert BI, Rewers M, Ziegler AG, Lernmark Å, Toppari J, Krischer JP, Akolkar B, Rich SS, She JX, TEDDY Study Group Tags: J Autoimmun Source Type: research

CD8+ T cells and IFN- γ induce autoimmune myelofibrosis in mice.
In conclusion, our results demonstrate that CD8+ T cells and IFN-γ are associated with autoimmune myelofibrosis, a finding that may allow targeting of CD8+ T cells and IFN-γ as a therapeutic targets. PMID: 29307587 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Yao Y, Li L, Yang SH, Gao CY, Liao LH, Xie YQ, Yin XY, Yang YQ, Fei YY, Lian ZX Tags: J Autoimmun Source Type: research

Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice.
es G Abstract Idiopathic steroid sensitive nephrotic syndrome (INS), the most frequent childhood nephropathy, is thought to be mediated by a circulating soluble factor that reversibly affects the renal protein sieving. The efficiency of rituximab therapy recently highlighted the involvement of B cells. Here we studied the involvement of a specific immunoglobulin G (IgG) in the disease. After plasma fractionation by size exclusion chromatography, a detachment of cultured podocyte was observed with one IgG-containing fraction from 47% patients in relapse, 9% of patients in remission and 0% of controls. Podocyte prot...
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Jamin A, Berthelot L, Couderc A, Chemouny JM, Boedec E, Dehoux L, Abbad L, Dossier C, Daugas E, Monteiro RC, Deschênes G Tags: J Autoimmun Source Type: research

Pathogenic IgG4 autoantibodies from endemic pemphigus foliaceus recognize a desmoglein-1 conformational epitope.
Abstract Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A129LNSMGQDLERPLELR144) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule. Mutation of Dsg1 residues M133 and Q135 reduced the binding of FS IgG4 autoantibodies...
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Evangelista F, Roth AJ, Prisayanh P, Temple BR, Li N, Qian Y, Culton DA, Liu Z, Harrison OJ, Brasch J, Honig B, Shapiro L, Diaz LA Tags: J Autoimmun Source Type: research

Th17 plasticity and its relevance to inflammatory bowel disease.
Abstract It is now clear that previously polarized T cells possess the ability to change their phenotype and repolarize towards different fates. This intrinsic flexibility is commonly referred to as plasticity and is influenced by the cytokine milieu, microbial products and products of metabolism which, in turn, regulate transcription factors and epigenetic machinery in the intestinal lamina propria. The intestinal immune system faces a particularly difficult challenge. It serves to protect the largest mucosal surface against infection and injury while maintaining a state of tolerance towards dietary antigens and ...
Source: Journal of Autoimmunity - December 28, 2017 Category: Allergy & Immunology Authors: Ueno A, Jeffery L, Kobayashi T, Hibi T, Ghosh S, Jijon H Tags: J Autoimmun Source Type: research

A cellular and molecular view of T helper 17  cell plasticity in autoimmunity.
A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun. 2017 Dec 21;: Authors: Stadhouders R, Lubberts E, Hendriks RW Abstract Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and ...
Source: Journal of Autoimmunity - December 21, 2017 Category: Allergy & Immunology Authors: Stadhouders R, Lubberts E, Hendriks RW Tags: J Autoimmun Source Type: research

Plasticity and heterogeneity of Th17 in immune-mediated kidney diseases.
Abstract Anti-neutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis, anti-glomerular basement membrane (GBM) glomerulonephritis and lupus nephritis are the most common causes of rapid progressive glomerulonephritis (RPGN) in the Western world. These aggressive forms of autoimmune kidney diseases significantly contribute to end-stage renal disease and are associated with high morbidity and mortality. Moreover, patients show significant heterogeneity with respect to clinical outcome and response to therapy. T cell infiltration is a morphological hallmark of RPGN and it is a critical driver of kidney...
Source: Journal of Autoimmunity - December 21, 2017 Category: Allergy & Immunology Authors: Krebs CF, Panzer U Tags: J Autoimmun Source Type: research

Critical role of ROCK2 activity in facilitating mucosal CD4+ T cell activation in inflammatory bowel disease.
In this study, we demonstrated that the levels of ROCK2, but not ROCK1, activity were significantly upregulated in peripheral blood mononuclear cells (PBMC) and inflamed mucosa from IBD patients using a ROCK activity assay, and that ROCK2 activity in intestinal mucosa was positively correlated with disease severity. Stimulation with TNF markedly upregulated ROCK2 activity in IBD CD4+ T cells through NF-κB signaling. Blockade of ROCK2 activity using Slx-2119 significantly suppressed proinflammatory cytokines in inflamed mucosa from IBD patients including IFX-unresponsive CD patients, and inhibited IBD CD4+ T cells to ...
Source: Journal of Autoimmunity - December 19, 2017 Category: Allergy & Immunology Authors: Yang W, Zhou G, Yu T, Chen L, Yu L, Guo Y, Cong Y, Liu Z Tags: J Autoimmun Source Type: research