Journal Sciences News
Transportation Research Part A: Policy and Practice
May 2018
Editorial Board
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5

May 2018
Perspective: Scientific and ethical concerns pertaining to animal models of autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA)
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Rohan Ameratunga, Daman Langguth, David Hawkes The autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) was first described in 2011. The aluminium containing adjuvants of vaccines were stated to be one of the main causes of the condition. Other disorders associated with ASIA include siliconosis, Gulf war syndrome, sick building syndrome and the macrophagic myositis syndrome. We have recently reviewed ASIA as defined by its authors. We have shown that the definition of ASIA is imprecise and includes all patients with an autoimmune disorder as well as potentially the entire population. Application of the Bradford Hill criteria for causality does not support ASIA as an outcome of exposure to aluminium containing adjuvants in vaccines. The advocates of ASIA highlight animal models as evidence for the existence of the disorder. However, as this review will demonstrate, animal models purporting to support the existence of ASIA have methodological, analytical and ethical flaws which, in our view, refute the existence of the condition. Three publications by the advocates of ASIA were recently retracted from peer-reviewed journals. We call for an immediate moratorium on animal experiments of ASIA until an independent inquiry has been conducted to determine the existence of a clinically relevant syndrome, identifiable as ASIA in humans.
May 2018
The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Yahel Segal, Shani Dahan, Kassem Sharif, Nicola Luigi Bragazzi, Abdulla Watad, Howard Amital Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity.
May 2018
Association between allelic variants of the human glucocorticoid receptor gene and autoimmune diseases: A systematic review and meta-analysis
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Cristian Herrera, Miguel Marcos, Cristina Carbonell, Jos
May 2018
Cryoglobulins: An update on detection, mechanisms and clinical contribution
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Marie-Nathalie Kolopp-Sarda, Pierre Miossec Cryoglobulins are immunoglobulins precipitating in cold condition. They are classified in 3 types according to the Brouet classification and may lead to vasculitis of small and medium size vessels. Vasculitis is related to vessel obstruction by monoclonal cryoglobulin aggregates in type I cryoglobulins and immune complex deposition in type II and III mixed cryoglobulins. This phenomenon is favored by low temperature, especially in skin, joints, and peripheral nerves, or increased cryoglobulin concentration in kidneys. For their detection, collection and clotting at 37°C are critical pre-analytical conditions. Cryoglobulin characterization and quantification are important to identify the underlying disease. Since detection and identification of cryoglobulins lack standardization, a protocol for such detection, characterization and quantification is proposed.
May 2018
The role of capillaroscopy and thermography in the assessment and management of Raynaud's phenomenon
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Ariane L. Herrick, Andrea Murray Most patients with Raynaud's phenomenon (RP) have “benign” primary RP (PRP), but a minority have an underlying cause, for example a connective tissue disease such as systemic sclerosis (SSc). Secondary RP can be associated with structural as well as functional digital vascular changes and can be very severe, potentially progressing to digital ulceration or gangrene. The first step in management is to establish why the patient has RP. This short review discusses the role of nailfold capillaroscopy and thermography in the assessment of RP. Nailfold capillaroscopy examines microvascular structure, which is normal in PRP but abnormal in most patients with SSc: the inclusion of abnormal nailfold capillaries into the 2013 classification criteria for SSc behoves clinicians diagnosing connective tissue disease to be familiar with the technique. For those without access to the gold standard of high magnification videocapillaroscopy, a low magnification dermatoscope or USB microscope can be used. Thermography measures surface temperature and is therefore an indirect measure of blood blow, assessing digital vascular function (abnormal in both PRP and SSc). Until now, the use of thermography has been mainly confined to specialist centres and used mainly in research: this may change with development of mobile phone thermography.
May 2018
A methodological review of induced animal models of autoimmune diseases
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Xinhua Yu, Frank Petersen Autoimmune disorders are characterized by a loss of immune tolerance and consequent autoimmunity-mediated disease manifestation. Experimental models are invaluable research tools helping us to understand disease pathogenesis and to search for novel therapeutics. Animal models of autoimmune diseases consist of two groups, spontaneous and induced models. In this review article, we focus on the induced models of autoimmune diseases. Due to the complex nature of autoimmune disorders, many strategies have been applied for the induction of corresponding experimental models in animals like monkeys, rabbits, rats, and mice. Methodologically, these strategies can be categorized into three categories, namely immunization with autoantigen, transfer of autoimmunity, and induction by environmental factors. In this review article, we aim to provide a comprehensive overview of the field of induced experimental autoimmune diseases. On the one hand, we describe and summarize the different strategies used for induction of experimental autoimmune disease. On the other hand, we discuss how to select a strategy for modeling human disease, including the choice of an appropriate species and method for such an approach.
May 2018
Optimizing conventional DMARD therapy for Sj
May 2018
Clinical and experimental evidence for targeting CD6 in immune-based disorders
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Marta Consuegra-Fern
May 2018
Contribution of sex steroids and prolactin to the modulation of T and B cells during autoimmunity
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Gabriela Recalde, Tamara Moreno-Sosa, Florencia Y
May 2018
Validation conform ISO-15189 of assays in the field of autoimmunity: Joint efforts in The Netherlands
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Leontine Mulder, Renate van der Molen, Carin Koelman, Ester van Leeuwen, Anja Roos, Jan Damoiseaux ISO 15189:2012 requires validation of methods used in the medical laboratory, and lists a series of performance parameters for consideration to include. Although these performance parameters are feasible for clinical chemistry analytes, application in the validation of autoimmunity tests is a challenge. Lack of gold standards or reference methods in combination with the scarcity of well-defined diagnostic samples of patients with rare diseases make validation of new assays difficult. The present manuscript describes the initiative of Dutch medical immunology laboratory specialists to combine efforts and perform multi-center validation studies of new assays in the field of autoimmunity. Validation data and reports are made available to interested Dutch laboratory specialists.
May 2018
Skeletal muscle cells actively shape (auto)immune responses
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Ali Maisam Afzali, Thomas M
Available online 13 April 2018
Letter to the Editor: Autoimmune pathogenic mechanisms in Amyotrophic Lateral Sclerosis
Publication date: May 2018
Source:Autoimmunity Reviews, Volume 17, Issue 5 Author(s): Antonio Greco, Massimo Ralli, Maurizio Inghilleri, Armando De Virgilio, Andrea Gallo, Marco de Vincentiis
Available online 8 April 2018
Analysis of microRNA expression in the thymus of Myasthenia Gravis patients opens new research avenues
Publication date: Available online 13 April 2018
Source:Autoimmunity Reviews Author(s): M
Available online 7 April 2018
Should rheumatoid factor (RF) (and antinuclear antibodies (ANA)) become routinary screening test for morbidities in the general population?
Publication date: Available online 8 April 2018
Source:Autoimmunity Reviews Author(s): Gianfranco Ferraccioli, Stefano Alivernini, Barbara Tolusso, Elisa Gremese
Available online 7 April 2018
Genetic variation and systemic lupus erythematosus: A field synopsis and systematic meta-analysis
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Dong Yeon Jeong, Sang Woo Lee, Young Ha Park, Ji Hoon Choi, Young Wook Kwon, Gabin Moon, Michael Eisenhut, Andreas Kronbichler, Jae Il Shin Systemic lupus erythematosus (SLE) is a multi-systemic severe autoimmune disease which results from the irreversible loss of self-tolerance and impaired molecular responses, especially an altered interferon signature. We synthesized all meta-analyses reporting a genetic association of SLE, and further investigated their validity to discover false positive results under Bayesian methods. We executed a PubMed search to extract the respective results regarding gene polymorphisms of SLE, published until June 30th 2017 and selected a single result per genetic variant among duplicates. Among 133 significant genotype comparisons, 45 (34%) were found noteworthy under both false positive report probability (FPRP) and Bayesian false discovery probability (BFDP). From the meta-analysis of genome-wide association studies (GWAS), we could confirm that all significant comparisons were noteworthy under both Bayesian approaches. Both approaches may be advantageous for determining whether the reported associations is genuine, especially for interpreting results from observational studies instead of GWAS whose significance was determined in a more strict manner. When determining results from GWAS with a p-value ranging between 0.05 and 5
Available online 7 April 2018
Autoimmune phenomena and disease in cancer patients treated with immune checkpoint inhibitors
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Milena Tocut, Ronen Brenner, Gisele Zandman-Goddard The discovery and approved treatment with immune checkpoint inhibitors (ICIs) for a variety of cancers has changed dramatically the morbidity and mortality rates for these patients. Despite the obvious benefits, their use is associated with unique immune-related adverse effects (irAEs), including autoimmune conditions such as: inflammatory arthritis, myositis, vasculitis and Sicca syndrome. The appearance of ICIs-induced autoimmune irAE requires from oncologists and rheumatologists a different approach to the identification and treatment of these conditions, which may differ from the classic and traditional approach to rheumatologic diseases. It should be taken into consideration that ICIs therapy in patients with preexisting autoimmunity could be possible, but with a cost of causing disease exacerbation. In this extensive review, we present the autoimmune irAEs, mostly as phenomena, but also as classic autoimmune diseases as well as therapeutic options for the side effects.
Available online 7 April 2018
The association of solid-phase assays to immunofluorescence increases the diagnostic accuracy for ANA screening in patients with autoimmune rheumatic diseases
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Nicola Bizzaro, Ignazio Brusca, Giulia Previtali, Maria Grazia Alessio, Massimo Daves, Stefan Platzgummer, Luigi Cinquanta, Giusy Paura, Maria Infantino, Mariangela Manfredi, Raffaella Faricelli, Danila Bassetti, Maura Musso, Gaia Deleonardi, Maria Teresa Trevisan, Antonella Radice, Marco Liguori, Tiziana Imbastaro, Fiorenza Pesente, Martina Fabris, Elio Tonutti
Available online 7 April 2018
Systemic lupus erythematosus and systemic sclerosis: All roads lead to platelets
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Marc Scherlinger, Vivien Guillotin, Marie-Elise Truchetet, C
Available online 7 April 2018
From HSV infection to erythema multiforme through autoimmune crossreactivity
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Alberta Lucchese Scientific and clinical data indicate that human herpes simplex virus 1 (HSV1) and, at a lesser extent, human herpes simplex virus 2 (HSV2) are factor(s) implicated in the development of erythema multiforme (EM). With a focus on oral EM, the present structured review of proteomic and epitope databases searched for the molecular basis that might link HSV1 and HSV2 infections to EM. It was found that a high number of peptides are shared between the two HSVs and human proteins related to the oral mucosa. Moreover, a great number of the shared peptides are also present in epitopes that have been experimentally validated as immunopositive in the human host. The results suggest the involvement of HSV infections in the induction of oral EM via a mechanism of autoimmune cross-reactivity and, in particular, highlight a potential major role for 180kDa bullous pemphigoid antigen and HSV1 infection in the genesis of crossreactions potentially conducive to EM.
Available online 7 April 2018
Efficacy and safety of rituximab in systemic sclerosis: French retrospective study and literature review
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Mathilde Thiebaut, David Launay, S
Available online 7 April 2018
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome – Evidence for an autoimmune disease
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Franziska Sotzny, Juli
Available online 7 April 2018
The role of ophthalmic imaging in central nervous system degeneration in systemic lupus erythematosus
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Arnaldo Dias-Santos, Rita Pinto Proen
Available online 6 April 2018
Antinuclear antibodies: Is the indirect immunofluorescence still the gold standard or should be replaced by solid phase assays?
Publication date: Available online 7 April 2018
Source:Autoimmunity Reviews Author(s): Dolores P
April 2018
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April 2018
Editorial Board
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4

April 2018
Beyond APECED: An update on the role of the autoimmune regulator gene (AIRE) in physiology and disease
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Giuseppina Conteduca, Francesco Indiveri, Gilberto Filaci, Simone Negrini The autoimmune regulator gene (AIRE) is a transcription factor expressed both in the thymus, by medullary thymic epithelial cells, and in secondary lymphoid organs. AIRE controls the local transcription of organ- specific proteins typically expressed in peripheral tissues, thus allowing the negative selection of self- reactive T cells. The crucial role played by AIRE in central immune tolerance emerged in the studies on the pathogenesis of Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy, a rare inherited polyendocrine/autoimmune disease. Thereafter, several studies found evidences indicating that AIRE impairment might be pathogenically involved in several autoimmune diseases and in tumorigenesis. In this review, we focus on recent advances relative to AIRE's effect on T cell development in physiology and disease. In particular, we address the following issues: 1) AIRE function and mTECs biology, 2) the impact of AIRE gene mutations in autoimmune diseases, and 3) the role of AIRE gene in anti-tumor immune response.
April 2018
Contribution of diagnostic tests for the etiological assessment of uveitis, data from the ULISSE study (Uveitis: Clinical and medicoeconomic evaluation of a standardized strategy of the etiological diagnosis)
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Pierre Grumet, Laurent Kodjikian, Audrey de Parisot, Marie-H
April 2018
Nailfold capillaroscopy in systemic lupus erythematosus: A systematic review and critical appraisal
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Maurizio Cutolo, Karin Melsens, Sara Wijnant, Francesca Ingegnoli, Kristof Thevissen, Filip De Keyser, Saskia Decuman, Ulf M
April 2018
Tocilizumab and refractory Takayasu disease: Four case reports and systematic review
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Paul Decker, Pierre Olivier, Jessie Risse, St
April 2018
IgE in lupus pathogenesis: Friends or foes?
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Jean-Fran
April 2018
Oxidized low density lipoproteins: The bridge between atherosclerosis and autoimmunity. Possible implications in accelerated atherosclerosis and for immune intervention in autoimmune rheumatic disorders
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Claudia Floriana Suciu, Marcella Prete, Piero Ruscitti, Elvira Favoino, Roberto Giacomelli, Federico Perosa Atherosclerotic vasculopathy is a multifactorial process causing vessels damage and cardiovascular diseases, the leading causes of death worldwide. Atherosclerotic plaque is the asymptomatic primary, elementary, lesion of atherosclerotic vasculopathy. Accumulation of the oxidized low-density lipoprotein (oxLDL) at sub endothelial sites is now recognized as one of the major trigger events in plaque formation. The concomitant presence at the plaque site of cells belonging to either natural or adaptive immunity, the detection of autoantibodies to oxLDL, the cross-reactivity of oxLDL with anti-phospholipid antibodies, in addition to the clinical evidence of increased rates of cardiovascular events in several rheumatic diseases, has stimulated intensive research to define interconnections between the immune system and traditional risk factors at the molecular levels in order to explain accelerated atherosclerosis. Here, we critically review the results of previous and recent studies, which have disclosed molecules of both innate or adaptive immunity involved in atherosclerosis, focusing primarily on B cells and autoantibodies, where data are more consolidated. Particular attention has also been paid to molecules that may be predictive markers of atherosclerosis progression and can be potential targets for immune intervention to delay the atherosclerotic process. The latter include CD20 antigen, molecules involved in the BAFF-BAFF receptor axis, inflammatory molecules and modified LDL. The successful results of a recent randomized controlled clinical trial targeting inflammasome with anti-IL1
April 2018
The imprint of salivary secretion in autoimmune disorders and related pathological conditions
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Kashi Raj Bhattarai, Raghupatil Junjappa, Mallikarjun Handigund, Hyung-Ryong Kim, Han-Jung Chae Xerostomia is a state of oral dryness associated with salivary gland dysfunction and is induced by stress, radiation and chemical therapy, various systemic and autoimmune diseases, and specific medications. Fluid secretion is interrupted by the stimulation of neurotransmitter-induced increase in cytosolic calcium ([Ca2+]i) in salivary gland acinar cells, prompting the mobilization of ion channels and their transporters. Salivary fluid and protein secretion are principally dependent on parasympathetic and sympathetic nerves. Various inflammatory cytokines allied with lymphocytic infiltration cause glandular damage and Sjogren's syndrome, an autoimmune exocrinopathy associated with hyposalivation. A defect in IP3Rs, a major calcium release channel, prompts inadequate agonist-induced [Ca2+]i in acinar cells and deters salivary flow. The store-operated calcium entry-mediated Ca2+ movement into the acini activates K+ and Cl
April 2018
Large-vessel involvement and aortic dilation in giant-cell arteritis. A multicenter study of 549 patients
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Hubert de Boysson, Aur
April 2018
The effect of non–TNF-targeted biologics and small molecules on insulin resistance in inflammatory arthritis
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Francesco Ursini, Emilio Russo, Piero Ruscitti, Roberto Giacomelli, Giovambattista De Sarro Inflammatory arthritides are chronic diseases characterised by an increase in cardiovascular risk, largely attributable to the synergy between high-grade systemic inflammation and an elevated prevalence of traditional cardiovascular risk factors. Amongst the latter, insulin resistance and type 2 diabetes (T2D) play a key position. Previous studies demonstrated a potential insulin-sensitizing effect of anti-TNF biologic medications. For converse, less is known about the role of newer biologics or small molecules. For this reason, we performed a systematic review of the literature in order to identify the available data on the effect on insulin resistance of non-TNF targeting biologics and small molecules approved for the treatment of inflammatory arthritides. The search strategy initially retrieved 486 records of which only 10 articles were selected for inclusion in the final review. According to the available evidence, some of the newest molecules, in particular tocilizumab and abatacept, may have a role in improving insulin sensitivity; for converse, anakinra-mediated effect on glucose metabolism may exploit different facets of T2D pathophysiology, such as the preservation of beta-cell function. However, the data available on this issue are largely inconsistent and future, adequately designed studies are still needed to clarify the differential impact of novel therapeutics on individual pathophysiological features of T2D and other emerging cardiovascular risk factors.
April 2018
Olfactory function in systemic lupus erythematosus and systemic sclerosis. A longitudinal study and review of the literature
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Mariana Freschi Bombini, Fernando Augusto Peres, Aline Tamires Lapa, Nail
April 2018
Cellular immune regulation in the pathogenesis of ANCA-associated vasculitides
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Anouk von Borstel, Jan Stephan Sanders, Abraham Rutgers, Coen A. Stegeman, Peter Heeringa, Wayel H. Abdulahad Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitides (AAV) are systemic autoimmune diseases characterized by necrotizing inflammation of small- to medium-sized blood vessels, affecting primarily the lungs and kidneys. Both animal and human studies show that the balance between inflammatory- and regulatory T- and B cells determines the AAV disease pathogenesis. Recent evidence shows malfunctioning of the regulatory lymphocyte compartment in AAV. In this review we summarize the immune regulatory properties of both T- and B cells in patients with AAV and discuss how aberrations herein might contribute to the disease pathogenesis.
April 2018
TCR
Available online 8 March 2018
Comment on the article entitled “Antineutrophil cytoplasmic antibody-associated vasculitides and IgG4-related disease: A new overlap syndrome” (Autoimmunity Reviews 16 (2017) 1036–1043)
Publication date: April 2018
Source:Autoimmunity Reviews, Volume 17, Issue 4 Author(s): Radjiv Goulabchand, Julien Delicque, Mathieu Gallo, Alain Le Quellec, Philippe Guilpain
March 2018
Solid phase assays versus automated indirect immunofluorescence for detection of antinuclear antibodies
Publication date: Available online 8 March 2018
Source:Autoimmunity Reviews Author(s): Jolien Claessens, Thibaut Belmondo, Ellen De Langhe, Rene Westhovens, Koen Poesen, Sophie H
March 2018
Editorial Board
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3

March 2018
Diagnosis and management of neuromyelitis optica spectrum disorders - An update
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Alice Bruscolini, Marta Sacchetti, Maurizio La Cava, Magda Gharbiya, Massimo Ralli, Alessandro Lambiase, Armando De Virgilio, Antonio Greco Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune conditions characterized by inflammatory involvement of the optic nerve, spinal cord and central nervous system. Novel evidence showed a key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the pathogenesis of NMOSD and, recently, new classification and diagnostic criteria have been adopted to facilitate an earlier identification and improve the management of these conditions. Diagnosis of NMOSD is currently based on clinical, neuroimaging and laboratory features. Standard treatment is based on the use of steroids and immunosuppressive drugs and aims to control the severity of acute attacks and to prevent relapses of the disease. This review gives an update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic criteria and both current and future therapeutic approaches.
March 2018
Cardiovascular involvement in systemic rheumatic diseases: An integrated view for the treating physicians
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Kwang Seob Lee, Andreas Kronbichler, Michael Eisenhut, Keum Hwa Lee, Jae Il Shin Systemic autoimmune diseases can affect various kinds of organs including the kidney, the skin, soft tissue and the bone. Among others, cardiovascular involvement in rheumatic diseases has been shown to affect myocardium, pericardium, cardiac vessels, conduction system and valves, eventually leading to increased mortality. In general, underlying chronic inflammation leads to premature atherosclerosis, but also other manifestations such as arrhythmia and heart failure may have a ‘silent’ progress. Traditional cardiovascular risk factors play a secondary role, while disease-specific factors (i.e. disease duration, severity, antibody positivity, persistent disease activity) can directly influence the cardiovascular system. Therefore, early diagnosis is critical to optimize management and to control inflammatory activity and recent data suggest that risk factors (i.e. hypercholesterolemia and hypertension) need intensive treatment as well. With the advent of immunosuppressive agents, most rheumatic diseases are well controlled on treatment, but information related to their cardioprotective efficacy is not well-defined. In this review, we focus on cardiovascular involvement in rheumatic diseases and highlight current evidence which should be of help for the treating physicians. Moreover, cardiotoxicity of immunosuppressive drugs is a rare issue and such potential adverse events will be briefly discussed.
March 2018
The anti-inflammatory effects of statins on patients with rheumatoid arthritis: A systemic review and meta-analysis of 15 randomized controlled trials
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Guo-min Li, Jie Zhao, Bing Li, Xiao-fei Zhang, Jian-xiong Ma, Xin-long Ma, Jun Liu Background Over the past several years, numerous studies investigated the anti-inflammatory effects of statin on patients with RA. However, the findings of the individual studies were often inconsistent or conflicting. Materials and methods The Pubmed, Web of Science, Embase, Cochrane Library and CNKI literature databases were searched in order to identify randomized controlled clinical trials where the association between the anti-inflammatory effect of statin and RA was investigated. Two researchers performed data extraction from eligible independently. Quality parameters and risk of bias in the included studies were assessed according to Cochrane's guidelines. The pooled Standardized Mean Difference (SMD) with a 95%CI was used to assess the anti-inflammatory effect of statin in patients with RA. Results Fifteen randomized controlled clinical, classified as “high quality” and with a relatively low risk of selection bias, were included in the meta-analysis. Of these, eight reported that there was no difference in the level of serum total lipids between the atorvastatin-treated and the conventional treatment group. However, the pooled analysis showed that atorvastatin could increase the level of serum amount of high-density lipoprotein (HDL) in RA patients by approximately x
March 2018
Genetic risk factors in thrombotic primary antiphospholipid syndrome: A systematic review with bioinformatic analyses
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Md. Asiful Islam, Shahad Saif Khandker, Fahmida Alam, Mohammad Amjad Kamal, Siew Hua Gan Background Antiphospholipid Syndrome (APS) is an autoimmune multifactorial disorder. Genetics is believed to play a contributory role in the pathogenesis of APS, especially in thrombosis development and pregnancy morbidity. In the last 20 years, extensive research on genetic contribution on APS indicates that APS is a polygenic disorder, where a number of genes are involved in the development of its clinical manifestations. Aims The aim of this systematic review is to evaluate the genetic risk factors in thrombotic primary APS. Additionally, to assess the common molecular functions, biological processes, pathways, interrelations with the gene encoded proteins and RNA-Seq-derived expression patterns over different organs of the associated genes via bioinformatic analyses. Methods Without restricting the year, a systematic search of English articles was conducted (up to 4th September 2017) using Web of Science, PubMed, Scopus, ScienceDirect and Google Scholar databases. Eligible studies were selected based on the inclusion criteria. Two researchers independently extracted the data from the included studies. Quality assessment of the included studies was carried out using a modified New-Castle Ottawa scale (NOS). Results From an initial search result of 2673 articles, 22 studies were included (1268 primary APS patients and 1649 healthy controls). Twenty-two genes were identified in which 16 were significantly associated with thrombosis in primary APS whereas six genes showed no significant association with thrombosis. Based on the NOS, 14 studies were of high quality while 6 were low quality studies. From the bioinformatic analyses, thrombin-activated receptor activity (q
March 2018
Altered B lymphocyte homeostasis and functions in systemic sclerosis
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Alexandra Forestier, Thomas Guerrier, Mathieu Jouvray, Jonathan Giovannelli, Guillaume Lef
March 2018
Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Ghita Harifi, Wared Nour-Eldine, Mohammad Hassan A. Noureldine, Mohammad Baker Berjaoui, Romy Kallas, Rita Khoury, Imad Uthman, Jamal Al-Saleh, Munther A. Khamashta First described in 1983, antiphospholipid syndrome (APS) is an autoimmune condition characterized by the occurrence of recurrent arterial and/or venous thrombosis, and/or pregnancy morbidity, in the setting of persistent presence of antiphospholipid antibodies (aPL). While thrombosis is the most well-known pathogenic mechanism in this disorder, the relevance of some other mechanisms such as arterial stenosis is being increasingly recognized. Arterial stenosis has been first described in the renal arteries in patients with APS, however intracranial and coeliac arteries can also be involved with various and treatable clinical manifestations. The underlying pathophysiology of this stenotic arterial vasculopathy is not fully understood but some recent studies revealed new insights into the molecular mechanism behind this endothelial cell activation in APS. In this review, we discuss these newly discovered mechanisms and highlight the diagnostic and therapeutic modalities of the APS related arterial stenosis.
March 2018
Bicaudal D2 is a novel autoantibody target in systemic sclerosis that shares a key epitope with CENP-A but has a distinct clinical phenotype
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Marvin J. Fritzler, Marie Hudson, May Y. Choi, Michael Mahler, Mianbo Wang, Chelsea Bentow, Jay Milo, Murray Baron We studied the clinical correlations and epitopes of autoantibodies directed to a novel autoantigen, Bicaudal D (BICD2), in systemic sclerosis (SSc) and reviewed its relationship to centromere protein A (CENP-A). 451 SSc sera were tested for anti-BICD2 using a paramagnetic bead immunoassay and then univariate and multivariate logistic regression was used to study the association between anti-BICD2 and demographic and clinical parameters as well as other SSc-related autoantibodies. Epitope mapping was performed on solid phase matrices. 25.7% (116/451) SSc sera were anti-BICD2 positive, of which 19.0% had single specificity anti-BICD2 and 81.0% had other autoantibodies, notably anti-CENP (83/94; 88.3%). Compared to anti-BICD2 negative subjects (335/451), single specificity anti-BICD2 subjects were more likely to have an inflammatory myopathy (IM; 31.8% vs. 9.6%, p=.004) and interstitial lung disease (ILD; 52.4% vs. 29.0%, p=.024). Epitope mapping revealed a serine- and proline-rich nonapeptide SPSPGSSLP comprising amino acids 606–614 of BICD2, shared with CENP-A but not CENP-B. We observed that autoantibodies to BICD2 represent a new biomarker as they were detected in patients without other SSc-specific autoantibodies and were the second most common autoantibody identified in this SSc cohort. Our data indicate that the major cross-reactive epitope is associated with anti-CENP-A but, unlike anti-CENP, single specificity anti-BICD2 antibodies associate with ILD and IM.
March 2018
Interaction between microbiome and host genetics in psoriatic arthritis
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Maria Sole Chimenti, Carlo Perricone, Lucia Novelli, Francesco Caso, Luisa Costa, Dimitrios Bogdanos, Paola Conigliaro, Paola Triggianese, Cinzia Ciccacci, Paola Borgiani, Roberto Perricone Psoriatic arthritis (PsA) is a chronic inflammatory joint disease, seen in combination with psoriasis. Both genetic and environmental factors are responsible for the development of PsA, however little is known about the different weight of these two distinctive components in the pathogenesis of the disease. Genomic variability in PsA is associated with the disease and/or some peculiar clinical phenotypes. Candidate genes involved are crucial in inflammation, immune system, and epithelial permeability. Moreover, the genesis and regulation of inflammation are influenced by the composition of the human intestinal microbiome that is able to modulate both mucosal and systemic immune system. It is possible that pro-inflammatory responses initiated in gut mucosa could contribute to the induction and progression of autoimmune conditions. Given such premises, the aim of this review is to summarize immune-mediated response and specific bacterial changes in the composition of fecal microbiota in PsA patients and to analyze the relationships between bacterial changes, immune system, and host genetic background.

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Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors
Publication date: March 2018
Source:Autoimmunity Reviews, Volume 17, Issue 3 Author(s): Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Schachter, Ronnie Shapira-Frommer, Gal Markel Background The use of immune checkpoint inhibitors (ICI) has grown incessantly since they were first approved in 2014. These monoclonal antibodies inhibit T cell activation, yielding a dramatic tumor response with improved survival. However, immunotherapy is frequently hampered by immune adverse events (iAE) such as hypophysitis, colitis, hepatitis, pneumonitis and rash. Until recently, rheumatic side effects were only infrequently reported. Aim To describe the rheumatic manifestations encountered among patients treated with ICIs in a large tertiary cancer center in Israel Methods The cancer center's patient registry was screened for patients who had ever been treated with ipilimumab, pembrolizumab and/or nivolumab with relevant data gathered from clinical charts. Results Rheumatic manifestations were encountered in 14 of 400 patients (3.5%) who had received immunotherapy between January 1st 2013 and April 30th, 2017. The most common rheumatic manifestation was inflammatory arthritis (85%) for which a third (4/11) had a clear cut predisposing factor such as a personal or family history of psoriasis, a prior episode of uveitis or ACPA positivity. Pulmonary sarcoidosis and biopsy-proven eosinophilic fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses
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