Journal Sciences News
Transportation Research Part A: Policy and Practice
Available online 17 January 2018
Genetic risk factors in thrombotic primary antiphospholipid syndrome: A systematic review with bioinformatic analyses
Publication date: Available online 19 January 2018
Source:Autoimmunity Reviews 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
Available online 16 January 2018
Genetics of immunoglobulin-A vasculitis (Henoch-Sch
Available online 16 January 2018
Altered B lymphocyte homeostasis and functions in systemic sclerosis
Publication date: Available online 16 January 2018
Source:Autoimmunity Reviews Author(s): Alexandra Forestier, Thomas Guerrier, Mathieu Jouvray, Jonathan Giovannelli, Guillaume Lef
Available online 16 January 2018
Arterial stenosis in antiphospholipid syndrome: Update on the unrevealed mechanisms of an endothelial disease
Publication date: Available online 16 January 2018
Source:Autoimmunity Reviews 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.
Available online 16 January 2018
Systemic sclerosis: Small mouth, big burden?
Publication date: Available online 16 January 2018
Source:Autoimmunity Reviews Author(s): Gaetano Isola, Marco Migliorati, Domenico Dalessandri, Giovanni Matarese
Available online 13 January 2018
Rheumatic manifestations among cancer patients treated with immune checkpoint inhibitors
Publication date: Available online 16 January 2018
Source:Autoimmunity Reviews Author(s): Merav Lidar, Eitan Giat, Daniela Garelick, Yuval Horowitz, Howard Amital, Yael Steinberg-Silman, Jacob Shachter, 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 eosinophilc fasciitis were diagnosed in two additional patients. Treatment with NSAIDS was mostly unsuccessful while steroid therapy was beneficial in doses
Available online 5 December 2017
Diagnosis and management of neuromyelitis optica spectrum disorders - an update
Publication date: Available online 13 January 2018
Source:Autoimmunity Reviews 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.
Available online 2 December 2017
Imaging modalities for the diagnosis and disease activity assessment of Takayasu's arteritis: A systematic review and meta-analysis
Publication date: Available online 5 December 2017
Source:Autoimmunity Reviews Author(s): Lillian Barra, Tahir Kanji, Jacqueline Malette, Christian Pagnoux Background Early diagnosis of Takayasu's Arteritis (TAK) and detection of disease activity may reduce the risk of vascular complications. The objective of this study was to determine the effectiveness of imaging modalities for the management of TAK. Methods MEDLINE and EMBASE were searched for studies of patients undergoing various imaging modalities for TAK diagnosis or to assess disease activity. We excluded case reports, reviews and case series with <10 patients. The methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). Random effects meta-analyses with inverse-variance weighting were performed. Results From the 1126 citations screened, 57 studies met our inclusion criteria. Many of the studies were of small sample size (average N=27), cross-sectional design and low methodological quality. Ultrasound (US) had a lower pooled sensitivity (SN) of 81% (95% CI: 69–89%) than Magnetic Resonance Angiography (MRA) with SN=92% (95% CI: 88–95%) for TAK diagnosis (by clinical criteria and/or X-Ray angiography). Both had high specificities (SP) of >90% for TAK diagnosis. Fewer studies investigated computed tomography angiography (CTA), but SN and SP for TAK diagnosis was high (>90%). The utility of vessel wall thickening and enhancement by MRA and CTA to predict disease activity varied across studies. The pooled SN and SP of 18F-fluorodeoxyglucose-Positron Emission Tomography (FDG-PET) for disease activity was 81% (95% CI: 69–89%) and 74% (95% CI: 55–86%), respectively. Conclusion US, CTA and/or MRA are effective for the diagnosis of TAK. The utility of these imaging modalities for assessing disease activity remains unclear.
Available online 2 December 2017
Clinical and immunological aspects of anti-peptidylarginine deiminase type 4 (anti-PAD4) autoantibodies in rheumatoid arthritis
Publication date: Available online 2 December 2017
Source:Autoimmunity Reviews Author(s): Zyanya Reyes-Castillo, Jos
Available online 2 December 2017
Pitfalls in the detection of citrullination and carbamylation
Publication date: Available online 2 December 2017
Source:Autoimmunity Reviews Author(s): M.K. Verheul, P.A. van Veelen, M.A.M. van Delft, A. de Ru, G.M.C. Janssen, T. Rispens, R.E.M. Toes, L.A. Trouw Carbamylation and citrullination are both post-translational modifications against which (auto)antibodies can be detected in sera of rheumatoid arthritis (RA) patients. Carbamylation is the chemical modification of a lysine into a homocitrulline, whereas citrullination is an enzymatic conversion of an arginine into a citrulline. It is difficult to distinguish between the two resulting amino acids due to similarities in structure. However, differentiation between citrulline and homocitrulline is important to understand the antigens that induce antibody production and to determine which modified antigens are present in target tissues. We have observed in literature that conclusions are frequently drawn regarding the citrullination or carbamylation of proteins based on reagents that are not able to distinguish between these two modifications. Therefore, we have analyzed a wide spectrum of methods and describe here which method we consider most optimal to distinguish between citrulline and homocitrulline. We have produced several carbamylated and citrullinated proteins and investigated the specificity of (commercial) antibodies by both ELISA and western blot. Furthermore, detection methods based on chemical modifications, such as the anti-modified citrulline-“Senshu” method and also mass spectrometry were investigated for their capacity to distinguish between carbamylation and citrullination. We observed that some antibodies are able to distinguish between carbamylation and citrullination, but an overlap in reactivity is often present in the commercially available anti-citrulline antibodies. Finally, we conclude that the use of mass spectrometry is currently essential to differentiate between citrullinated and carbamylated proteins present in complex biological samples.
December 2017
Scleroderma skin ulcers definition, classification and treatment strategies our experience and review of the literature
Publication date: Available online 2 December 2017
Source:Autoimmunity Reviews Author(s): Dilia Giuggioli, Andreina Manfredi, Federica Lumetti, Michele Colaci, Clodoveo Ferri Background Skin ulcers (SU) are one of the most frequent manifestations of systemic sclerosis (SSc). SSc-SU are very painful, often persistent and recurrent; they may lead to marked impairment of patient's activities and quality of life. Despite their severe impact on the whole SSc patient's management, the proposed definition, classification criteria, and therapeutic strategies of SSc-SU are still controversial. Objective The present study aimed to elaborate a comprehensive proposal of definition, classification, and therapeutic strategy of SSc-SU on the basis of our long-term single center experience along with a careful revision of the world literature on the same topic. Methods A series of 282 SSc patients (254 females and 28 males; 84% with limited and 16% diffuse cutaneous SSc; mean age of 51.5±13.9SD at SSc onset; mean follow-up 5.8±4.6SDyears) enrolled during the last decade at our Rheumatology Unit were retrospectively evaluated with specific attention to SSc-SU. The SSc-SU were classified in 5 subtypes according to prominent pathogenetic mechanism(s) and localization, namely 1. digital ulcers (DU) of the hands or feet, 2. SU on bony prominence, 3. SU on calcinosis, 4. SU of lower limbs, and 5. DU presenting with gangrene. This latter is a very harmful evolution of both DU of the hands and feet needing a differential diagnosis with critical limb ischemia. Results During the follow up period, one or more episodes of SSc-SU were recorded in over half patients (156/282, 55%); skin lesions were often recurrent and difficult-to-heal because of local complications, mainly infections (67.3%), in some cases associated to osteomyelitis (19.2%), gangrene (16%), and/or amputation (11.5%). SSc-SU were significantly associated with lower patients' mean age at the disease onset (p=0.024), male gender (p=0.03), diffuse cutaneous subset (p=0.015), calcinosis (p=0.002), telangiectasia (p=0.008), melanodermia (p<0.001), abnormal PAPs (p=0.036), and/or altered inflammation reactant (CRP, p=0.001). Therapeutic strategy of SSc-SU included both systemic and local pharmacological treatments with particular attention to complicating infections and chronic/procedural pain, as well as a number of non-pharmacological measures. Integrated local treatments were often decisive for the SSc-SU healing; they were mainly based on the wound bed preparation principles that are summarized in the acronym TIME (necrotic Tissue, Infection/Inflammation, Moisture balance, and Epithelization). The updated review of the literature focusing on this challenging issue was analyzed in comparison with our experience. Conclusions The recent advancement of knowledge and management strategies of SSc-SU achieved during the last years lead to the clear-cut improvement of patients' quality of life and reduced long-term disability.
December 2017
Novelties in the field of autoimmunity – 1st Saint Petersburg congress of autoimmunity, the bridge between east and west
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Shani Dahan, Yahel Segal, Abdulla Watad, Shir Azrielant, Asaf Shemer, Dror Maymon, Yuri I. Stroev, Polina A. Sobolevskaya, Elena A. Korneva, Miri Blank, Boris Gilburd, Ora Shovman, Howard Amital, Michael Ehrenfeld, Amir Tanay, Shay Kivity, Elon Pras, Joav Chapman, Jan Damoiseaux, Ricard Cervera, Chaim Putterman, Iziaslav Shapiro, Luc Mouthon, Roberto Perricone, Nicola Bizzaro, Omry Koren, Gabriela Riemekasten, Valeriy A. Chereshnev, Vadim I. Mazurov, Mark Goloviznin, Victor Gurevich, Leonid P. Churilov, Yehuda Shoenfeld
December 2017
The management of first-line biologic therapy failures in rheumatoid arthritis: Current practice and future perspectives
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Ennio Giulio Favalli, Maria Gabriella Raimondo, Andrea Becciolini, Chiara Crotti, Martina Biggioggero, Roberto Caporali The introduction of biologic disease–modifying anti-rheumatic drugs (bDMARDs) has dramatically changed the management of rheumatoid arthritis (RA). However, in a real-life setting about 30–40% of bDMARD treated patients experience drug discontinuation because of either inefficacy or adverse events. According to international recommendations, to date the best strategy for managing first-line bDMARD failures has not been defined yet and available data (especially on TNF inhibitors [TNFis]) seem to drive toward a personalized approach for the individual patient. Some TNFi partial responders may benefit from optimization of concomitant methotrexate therapy or from switching to a different concomitant sDMARD such as leflunomide. Conversely, apart from infliximab, TNFi dose escalation seems to be poor efficacious and poor cost-effective compared with alternative strategies. Albeit counterintuitive, the use of a second TNFi after the failure of the first-one (cycling strategy) is supported by clear evidences and has become widespread in the 2000s as the result of the limited alternative options till the introduction of bDMARDs with a mechanism of action other than TNF blockade. Nowadays, the use of abatacept, rituximab, tocilizumab, or JAK inhibitors as second-line agent (swapping strategy) is strongly supported by RCTs and real-life experiences. In the absence of head-to-head trials directly comparing these two strategies, meta-analyses of separated RCTs failed to find significant differences in favor of one or another choice. However, results from most observational studies, including well designed prospective pragmatic randomised analyses, demonstrated the superiority of swapping over cycling approach, whereas only few studies reported a comparable effectiveness. In this review, we aimed to critically analyze all the potential therapeutic options for the treatment of first-line bDMARD failures in order to provide a comprehensive overview of available strategies to be applied in clinical practice.
December 2017
Autoimmune comorbidity in chronic spontaneous urticaria: A systematic review
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Pavel Kolkhir, Elena Borzova, Clive Grattan, Riccardo Asero, Dmitry Pogorelov, Marcus Maurer Background and objective Numerous autoimmune diseases (AIDs) have been linked to chronic spontaneous urticaria (CSU). Here, we provide the first extensive and comprehensive evaluation of the prevalence of AIDs in patients with CSU and vice versa. Methods A Pubmed and Google Scholar search was performed to identify studies reporting the prevalence of various AIDs in CSU and vice versa published before April 2017. Results The prevalence of individual AIDs in CSU is increased (
December 2017
Interleukin-22 in human inflammatory diseases and viral infections
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Arezoo Gowhari Shabgah, Jamshid Gholizadeh Navashenaq, Omid Gohari Shabgah, Hamed Mohammadi, Amirhossein Sahebkar Interleukin-22 (IL22) is one of the members of IL10 family. Elevated levels of this cytokine can be seen in diseases caused by T lymphocytes, such as Psoriasis, Rheumatoid arthritis, interstitial lung diseases. IL22 is produced by different cells in both innate and acquired immunities. Different types of T cells are able to produce IL22, but the major IL22-producing T-cell is the TCD4. TH22 cell is a new line of TCD4 cells, which differentiated from naive T cells in the presence of TNF
December 2017
Cogan syndrome: Characteristics, outcome and treatment in a French nationwide retrospective study and literature review
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Charlotte Durtette, Eric Hachulla, Matthieu Resche-Rigon, Thomas Papo, Thierry Z
December 2017
The inter-observer reading variability in anti-nuclear antibodies indirect (ANA) immunofluorescence test: A multicenter evaluation and a review of the literature
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): A Rigon, M. Infantino, M. Merone, G. Iannello, A. Tincani, I. Cavazzana, N. Carabellese, A. Radice, M. Manfredi, P. Soda, A. Afeltra Recently there has been an increase demand for Computer-Aided Diagnosis (CAD) tools to support clinicians in the field of Indirect ImmunoFluorescence (IIF), as the novel digital imaging reading approach can help to overcome the reader subjectivity. Nevertheless, a large multicenter evaluation of the inter-observer reading variability in this field is still missing. This work fills this gap as we evaluated 556 consecutive samples, for a total of 1679 images, collected in three laboratories with IIF expertise using HEp-2 cell substrate (MBL) at 1:80 screening dilution according to conventional procedures. In each laboratory, the images were blindly classified by two experts into three intensity classes: positive, negative, and weak positive. Positive and weak positive ANA-IIF results were categorized by the predominant fluorescence pattern among six main classes. Data were pairwise analyzed and the inter-observer reading variability was measured by Cohen's kappa test, revealing a pairwise agreement little further away than substantial both for fluorescence intensity and for staining pattern recognition (k=0.602 and k=0.627, respectively). We also noticed that the inter-observer reading variability decreases when it is measured with respect to a gold standard classification computed on the basis of labels assigned by the three laboratories. These data show that laboratory agreement improves using digital images and comparing each single human evaluation to potential reference data, suggesting that a solid gold standard is essential to properly make use of CAD systems in routine work lab.
December 2017
HLA-DRB1 alleles and juvenile idiopathic arthritis: Diagnostic clues emerging from a meta-analysis
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Annalisa De Silvestri, Cristina Capittini, Dimitri Poddighe, Gian Luigi Marseglia, Luca Mascaretti, Elena Bevilacqua, Valeria Scotti, Chiara Rebuffi, Annamaria Pasi, Miryam Martinetti, Carmine Tinelli Juvenile Idiopathic Arthritis (JIA) is characterized with a variable pattern of articular involvement and systemic symptoms and, thus, it has been classified in several subtypes. Genetic predisposition to JIA is mainly due to HLA class II molecules (HLA-DRB1, HLA-DPB1), although HLA class I molecules and non-HLA genes have been implicated, too. Here, we carried out a meta-analysis including selected studies designed to assess HLA genetic background of JIA patients, compared to healthy controls; particularly, we focused our attention on HLA-DRB1. In summary, our meta-analysis showed four main findings regarding HLA-DRB1 locus as a genetic factor of JIA: i) HLA-DRB1*08 is a strong factor predisposing to JIA, both for oligo-articular and poly-articular forms (oJIA>pJIA); ii) HLA-DRB1*01 and HLA-DRB1*04 may be involved in the genetic predisposition of Rheumatoid Factor (RF) positive forms of JIA; iii) HLA-DRB1*11 was confirmed to be predisposing to oligo-articular JIA; iv) HLA-DRB1*04 was confirmed to have a role in systemic JIA. Importantly, RF positivity seems to select the JIA clinical subset with the strongest immunogenetic similarities with adult rheumatoid arthritis.
December 2017
Zika virus and autoimmunity. One-step forward
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Diana M. Monsalve, Yovana Pacheco, Yeny Acosta-Ampudia, Yhojan Rodr
December 2017
New insights in the pathogenesis of immunoglobulin A vasculitis (Henoch-Sch
December 2017
Uveitis: Diagnostic work-up. A literature review and recommendations from an expert committee
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Pascal S
December 2017
Rheumatic diseases and autoimmune vascular dementia
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Fabiola Atzeni, Nicol
Available online 28 November 2017
The roles and applications of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours
Publication date: December 2017
Source:Autoimmunity Reviews, Volume 16, Issue 12 Author(s): Jing Wu, Xiaobo Li, Wuqi Song, Yong Fang, Li Yu, Siyuan Liu, Leonid P. Churilov, Fengmin Zhang The existence of autoantibodies towards an individual's own proteins or nucleic acids has been established for more than 100years, and for a long period, these autoantibodies have been believed to be closely associated with autoimmune diseases. However, in recent years, researchers have become more interested in the role and application of autoantibodies in progression, diagnosis, treatment and prognosis of human malignant tumours. Over the past few decades, numerous epidemiological studies have shown that the risk of certain cancers is significantly altered (increased or decreased) in patients with autoimmune diseases, which suggests that autoantibodies may play either promoting or suppressing roles in cancer progression. The idea that autoantibodies are directly involved in tumour progression gains special support by the findings that some antibodies secreted by a variety of cancer cells can promote their proliferation and metastasis. Because the cancer cells generate cell antigenic changes (neoantigens), which trigger the immune system to produce autoantibodies, serum autoantibodies against tumour-associated antigens have been established as a novel type of cancer biomarkers and have been extensively studied in different types of cancer. The autoantibodies as biomarkers in cancer diagnosis are not only more sensitive and specific than antigens, but also could appear before clinical evidences of the tumours, thus disclosing them. The observations that cancer risk is lower in patients with some autoimmune diseases suggest that certain autoantibodies may be protective from certain cancers. Moreover, the presence of autoantibodies in healthy individuals implies that it could be safe to employ autoantibodies to treat cancer. Of note, an autoantibodies derived from lupus murine model received much attention due to their selective cytotoxicity for malignant tumour cell without harming normal ones. These studies showed the therapeutic value of autoantibodies in cancer. In this review, we revisited the pathological or protective role of autoantibodies in cancer progression, summarize the application of autoantibodies in cancer diagnosis and prognosis, and discuss the value of autoantibodies in cancer therapy. The studies established to date suggest that autoantibodies not only regulate cancer progression but also promise to be valuable instruments in oncological diagnosis and therapy.
Available online 28 November 2017
Imaging aspects of interstitial lung disease in patients with rheumatoid arthritis: Literature review
Publication date: Available online 28 November 2017
Source:Autoimmunity Reviews Author(s): Alexandra Balbir-Gurman, Ludmila Guralnik, Mordechai Yigla, Yolanda Braun-Moscovici, Emilia Hardak Objective Interstitial lung disease (ILD) is a frequent and severe complication of rheumatoid arthritis (RA), resulting in pulmonary fibrosis (PF) and respiratory failure. Methods Chest computed tomography (CT-c) or high resolution CT (HRCT) is the main modality for assessment of ILD. We performed a systematic literature review on CT-c/HRCT findings in patients with ILD-RA, using the MEDLINE database for the period from 1991 to 2015. Results Findings on CT-c/HRCT attributed to ILD-RA are variable (ground glass opacities, reticular and nodular pattern, as well as a combined pattern of emphysema and PF). Correlation of CT-c/HRCT findings with clinical data is inconsistent. Conclusions ILD-RA is part of a general autoimmune inflammation and should be integrated into the decision-making process for the treatment of RA. There is an unmet need to design an algorithm which will allow prediction of CT-c changes compatible with ILD-RA with a high probability. Hopefully, this will enable treating patients with ILD-RA early, with possible halting of the progression of ILD-RA toward PF.
Available online 28 November 2017
Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis
Publication date: Available online 28 November 2017
Source:Autoimmunity Reviews Author(s): Laura Calvo-Barreiro, Herena Eixarch, Xavier Montalban, Carmen Espejo The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.
Available online 26 November 2017
A concise review of significantly modified serological biomarkers in giant cell arteritis, as detected by different methods
Publication date: Available online 28 November 2017
Source:Autoimmunity Reviews Author(s): B. Burja, T. Kuret, S. Sodin-Semrl, K. Lakota,
Available online 24 November 2017
NK cells in autoimmune diseases: Linking innate and adaptive immune responses
Publication date: Available online 26 November 2017
Source:Autoimmunity Reviews Author(s): Elena Gianchecchi, Domenico Vittorio Delfino, Alessandra Fierabracci The pathogenesis of autoimmunity remains to be fully elucidated, although the contribution of genetic and environmental factors is generally recognized. Despite autoimmune conditions are principally due to T and B lymphocytes, NK cells also appear to play a role in the promotion and/or maintenance of altered adaptive immune responses or in peripheral tolerance mechanisms. Although NK cells are components of the innate immune system, they shows characteristics of the adaptive immune system, such as the expansion of pathogen-specific cells, the generation of long-lasting “memory” cells able to persist upon cognate antigen encounter, and the possibility to induce an increased secondary recall response to re-challenge. Human NK cells are generally identified as CD56+ CD3
Available online 24 November 2017
Clinical and microbiological characteristics of the infections in patients treated with rituximab for autoimmune and/or malignant hematological disorders
Publication date: Available online 24 November 2017
Source:Autoimmunity Reviews Author(s): Jean-Jacques Tudesq, Guillaume Cartron, Sophie Rivi
Available online 24 November 2017
Childhood- versus adult-onset ANCA-associated vasculitides: A nested, matched case–control study from the French Vasculitis Study Group Registry
Publication date: Available online 24 November 2017
Source:Autoimmunity Reviews Author(s): Michele Iudici, Christian Pagnoux, Pierre Quartier, Matthias B
Available online 24 November 2017
Curcumin: A natural modulator of immune cells in systemic lupus erythematosus
Publication date: Available online 24 November 2017
Source:Autoimmunity Reviews Author(s): Amir Abbas Momtazi-Borojeni, Saeed Mohammadian Haftcheshmeh, Seyed-Alireza Esmaeili, Thomas P. Johnston, Elham Abdollahi, Amirhossein Sahebkar Curcumin is a polyphenol natural product isolated from turmeric, interacting with different cellular and molecular targets and, consequently, showing a wide range of pharmacological effects. Recent preclinical and clinical trials have revealed immunomodulatory properties of curcumin that arise from its effects on immune cells and mediators involved in the immune response, such as various T-lymphocyte subsets and dendritic cells, as well as different inflammatory cytokines. Systemic lupus erythematosus (SLE) is an inflammatory, chronic autoimmune-mediated disease characterized by the presence of autoantibodies, deposition of immune complexes in various organs, recruitment of autoreactive and inflammatory T cells, and excessive levels of plasma proinflammatory cytokines. The function and numbers of dendritic cells and T cell subsets, such as T helper 1 (Th1), Th17, and regulatory T cells have been found to be significantly altered in SLE. In the present report, we reviewed the results of in vitro, experimental (pre-clinical), and clinical studies pertaining to the modulatory effects that curcumin produces on the function and numbers of dendritic cells and T cell subsets, as well as relevant cytokines that participate in SLE.
Available online 4 November 2017
Belimumab in the treatment of systemic lupus erythematous: An evidence based review of its place in therapy
Publication date: Available online 24 November 2017
Source:Autoimmunity Reviews Author(s): Frederico Marcondes, Morton Scheinberg Introduction Systemic lupus erythematous is an autoimmune disease with diverse clinical features and has its development associated with a complexity of genetic, hormonal and environmental factors and the development of autoantibodies. Identification of new treatments is currently an area of intense investigation. Belimumab is the first biologic approved for the treatment of the disease inhibiting the excessive B cell activity observed in these patients and consequently reduction of autoantibodies. Aim To review the current transition of the evidence available of its use in real life patients with persistent active disease while on conventional therapies. Evidence The results observed on the large series of patients (over 50 patients) followed for at least six months confirm the observations from phase 3 trials. In clinical practice close to two third of the patients remained on belimumab and one third discontinued mostly due to evaluation by the doctor or the patient or both of no detectable positive response. The presence of adverse events was considerably low and the subgroups with skin and joint manifestations appear to benefit the most. Daily steroid use is usually reduced to a significantly low when compared with the intake before introduction of the biologic Although not seen on trials in real life the addition of belimumab to the conventional therapy in lupus nephritis is being reported in several patients. Cost of the medication is still an issue that hampers its use. Further evidence of its use in certain specific groups is under investigation and its results should shed light on additional indications. Place in therapy Considering what is currently published on the evidence here reviewed in the use of belimumab in clinical practice it is our understanding that belimumab it will be gradually incorporated in the armamentarium of treatment not necessarily on refractory patients. We believe that with the upcoming of the subcutaneous route in the near future should also help in widen the use of the belimumab to be considered in first line combination set ups.
Available online 4 November 2017
Targeting interferons and their pathways in systemic lupus erythematosus
Publication date: Available online 4 November 2017
Source:Autoimmunity Reviews Author(s): Fran
Available online 3 November 2017
The immunobiology and clinical features of type 1 autoimmune polyglandular syndrome (APS-1)
Publication date: Available online 4 November 2017
Source:Autoimmunity Reviews Author(s): Can-Jie Guo, Patrick S.C. Leung, Weici Zhang, Xiong Ma, M. Eric Gershwin Autoimmune Polyglandular Syndrome type 1 (APS-1) is a subtype of the autoimmune polyendocrine syndrome characterized by the simultaneous or sequential dysfunction of multiple endocrine or non-endocrine glands. A clinical diagnosis of APS-1 is typically based on the presence of at least two of three following criteria: chronic mucocutaneous candidiasis, hypoparathyroidism and adrenal insufficiency. The first identified causative mutated gene for APS-1 is autoimmune regulator (AIRE) encoding a critical transcription factor, which is primarily expressed in the medullary thymic epithelial cells (mTECs) for generating central immune tolerance. A wide range of chronic, debilitating complications, with no obvious correlation with genetics, makes a diagnosis of APS-1 challenging early in the disease course. Managing APS-1 is difficult due to its complexity, especially the intricate relationships within manifestations and genetic mutations. The past decades have witnessed dramatic progress in elucidating the function of AIRE and conducting large-scale cohort studies in APS-1. However, no clear evidence-based guidelines have been established in APS-1. In this review, we provide a detailed critical overview of the study history, epidemiology, clinical features, and related mechanisms of autoimmunity in APS-1, as well as currently available therapies for this autoimmune disorder.
Available online 3 November 2017
Can we withdraw immunosuppressants in patients with lupus nephritis in remission? An expert debate
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Gabriella Moroni, Mariele Gatto, Francesca Raffiotta, Valentina Binda, Eleni Frangou, Liz Lightstone, Dimitrios T. Boumpas Lupus nephritis (LN) treatment requires an initial intensive period of therapy followed by a long-term maintenance treatment in order to stabilize disease control and eventually reach renal remission. In this section, Authors discuss the feasibility of safely lowering and even suspending maintenance therapy in LN patients having entered remission, highlighting hurdles in predicting the depth and durability of disease quiescence together with the need for minimizing potentially toxic therapies. Even though no firm conclusions can still be drawn, the treating physician has to find the wise balance between disease control and treatment-related drawbacks by following patients closely and recognizing as early as possible the ones who are likely to reach a deep and durable renal remission; there is consensus that is these are the only patients in whom a potential safe complete withdrawal can be foreseen so far.
Available online 3 November 2017
Cocaine and ANCA associated vasculitis-like syndromes – A case series
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Sujith Subesinghe, Sander van Leuven, Leena Yalakki, Shirish Sangle, David D'Cruz Objectives We analysed the spectrum of clinical manifestations of cocaine associated pseudovasculitis. Methods Clinical, serological, radiological and histological features of 14 patients with cocaine pseudovasculitis syndromes were included. Results Twelve patients had significant sinus thickening or erosive disease. Other multi-system manifestations included vasculitic rashes, pulmonary lesions and peripheral neuropathy. All patients had positive ANCA titres at presentation. All patients were managed with corticosteroids +/
Available online 3 November 2017
Is undifferentiated spondyloarthritis a discrete entity? A debate
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Atul Deodhar, Pierre Miossec, Xenofon Baraliakos The concept of undifferentiated spondyloarthritis has been introduced recently to describe a clinical setting where the classical features of spondyloarthritis (SpA) are not fully present. Whether this is a discrete entity was the basis of a debate during the 4th International Congress on Controversies in Rheumatology & Autoimmunity held in Bologna, Italy 9–11 March 2017. The pro and con aspects of the debate are presented. The implications of the debate are important ranging from diagnostic aspects to consequences for the society and the payers.
Available online 3 November 2017
Brain diffusion tensor MRI in systematic lupus erythematosus: A systematic review
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Beatriz Lavras Costallat, Daniel Miranda Ferreira, Aline Tamires Lapa, Let
Available online 3 November 2017
Are the ACR 2010 diagnostic criteria for fibromyalgia better than the 1990 criteria?
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Piercarlo Sarzi-Puttini, Fabiola Atzeni, Ignazio Francesco Masala, Fausto Salaffi, Joab Chapman, Ernest Choy Fibromyalgia (FM) is difficult to diagnose and manage chronic pain condition whose symptoms have no clear pathophysiological cause, although it is thought that patient hypersensitivity to a range of stimuli may give rise to mechanical hyperalgesia as a result of altered central nociceptive processing. The 1990 American College of Rheumatology (ACR) classification criteria, which have been widely used in clinical practice, require the existence of chronic widespread pain (CWP) for >3months, and the presence of at least 11 out of 18 specified tender points upon digital palpation, although this latter criterion has long been criticised. The newer 2010 ACR diagnostic criteria state that FM can be defined as CWP associated with somatic symptoms, and recommend the use of a widespread pain index and a scale to rate symptom severity. A modified version of the 2010 criteria removed the physician assessment of the extent of somatic symptoms and replaced it by a summary score of three self-reported symptoms, thus making it easier to use while maintaining its sensitivity. This review discusses the advantages and limitations of all of these criteria.
Available online 3 November 2017
Physical activity and autoimmune diseases: Get moving and manage the disease
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Kassem Sharif, Abdulla Watad, Nicola Luigi Bragazzi, Micheal Lichtbroun, Howard Amital, Yehuda Shoenfeld Physical activity, by definition, is any skeletal muscle body movement that results in energy expenditure. In the last few decades, a plethora of scientific evidences have accumulated and confirmed the beneficial role of physical activity as a modifiable risk factor for a wide variety of chronic diseases including cardiovascular diseases (CVDs), diabetes mellitus and cancer, among others. Autoimmune diseases are a heterogeneous group of chronic diseases, which occur secondary to loss of self-antigen tolerance. With the advent of biological therapies, better outcomes have recently been noted in the management of autoimmune diseases. Nonetheless, recent research highlights the salient role of modifiable behaviors such as physical inactivity on various aspects of the immune system and autoimmune diseases. Physical activity leads to a significant elevation in T-regulatory cells, decreased immunoglobulin secretion and produces a shift in the Th1/Th2 balance to a decreased Th1 cell production. Moreover, physical activity has been proven to promote the release of IL-6 from muscles. IL-6 released from muscles functions as a myokine and has been shown to induce an anti-inflammatory response through IL-10 secretion and IL-1
Available online 3 November 2017
Can we manage lupus nephritis without chronic corticosteroids administration?
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Liz Lightstone, Andrea Doria, Hannah Wilson, Frank L. Ward, Maddalena Larosa, Joanne M. Bargman The outcome of lupus nephritis (LN) has changed since the introduction of glucocorticoids (GCs), which dramatically reduced the mortality related to one of the most severe complications of systemic lupus erythematosus (SLE). Since the 1950
Available online 3 November 2017
Controversies in Rheumatology and Autoimmunity: Approaching the truth by the discussion
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Andrea Doria, Mariele Gatto, Luca Iaccarino, Piercarlo Sarzi-Puttini
Available online 3 November 2017
Vitamin D and systemic lupus erythematosus - The hype and the hope
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Yehuda Shoenfeld, Roberto Giacomelli, Shir Azrielant, Onorina Berardicurti, John A. Reynolds, Ian N. Bruce Over the past 20years, much has been written about the potential role of vitamin D in on adverse health outcomes. In recent years, evidence has accumulated regarding the effect of vitamin D on the immune system, and its different cells. Some studies have noted lower vitamin D concentrations in patients with SLE. These epidemiological data still not answer the question: is vitamin D deficiency the cause or the effect? To answer this, we will discuss the association between vitamin D deficiency and SLE and review the evidence from interventional studies.
November 2017
TNF inhibitors in rheumatoid arthritis and spondyloarthritis: Are they the same?
Publication date: Available online 3 November 2017
Source:Autoimmunity Reviews Author(s): Andrea Rubbert-Roth, Fabiola Atzeni, Ignazio Francesco Masala, Roberto Caporali, Carlomaurizio Montecucco, Piercarlo Sarzi-Puttini The advent of anti-tumour necrosis factor (TNF) drugs for rheumatoid arthritis (RA) or spondyloarthritis (SpA) has revolutionised the approach to patients with active disease who do not respond to conventional therapy. Although there are differences in their structure, morphology, pharmacokinetic properties and activity, all anti-TNF drugs ultimately neutralise the TNF
November 2017
Unresolved and critical issues in autoimmune rheumatic diseases
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Andrea Doria, Mariele Gatto, Luca Iaccarino, Piercarlo Sarzi-Puttini
November 2017
Is ACPA positivity the main driver for rheumatoid arthritis treatment? Pros and cons
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Stefano Alivernini, Mauro Galeazzi, Hagit Peleg, Barbara Tolusso, Elisa Gremese, Gianfranco Ferraccioli, Yaakov Naparstek Rheumatoid Arthritis (RA) is an autoimmune chronic disease that is characterized by the positivity of various antibodies, the most specific being autoantibodies against citrullinated antigens (ACPA). Despite ACPA are not arthritogenic by themselves, ACPA positive individuals have high risk of RA development and ACPA positivity is associated with severe erosive phenotype and higher mortality rate compared to seronegative RA. Moreover, ACPA status is associated with favorable response to biologics targeting pathways involving autoantibody producing cells as B lymphocytes. In the current review we have discussed the pros and cons on the available scientific evidences, regarding the diagnostic, prognostic and management implications of ACPAs in RA.
November 2017
Primary thromboprophylaxis with low-dose aspirin and antiphospholipid antibodies: Pro's and Con's
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Laurent Arnaud, Fabrizio Conti, Laura Massaro, Gentian Denas, Fran
November 2017
Can we withdraw anticoagulation in patients with antiphospholipid syndrome after seroconvertion?
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): S. Sciascia, E. Coloma-Baz
November 2017
Should we treat congenital heart block with fluorinated corticosteroids?
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Antonio Brucato, Angela Tincani, Micaela Fredi, Silvia Breda, Veronique Ramoni, Nathalie Morel, Nathalie Costedoat-Chalumeau
November 2017
The new targeted therapy in systemic lupus erythematosus: Is the glass half-full or half-empty?
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Andrea Doria, Ricard Cervera, Mariele Gatto, Gamal Chehab, Matthias Schneider Biologic therapy is still limited in lupus, where chronic steroid exposure and wide-spectrum immunosuppression are major triggers of organ damage. In this viewpoint, the authors summarize their views for a “half-full or half-empty” glass on targeted therapy in SLE. The are several reasons for seeing the glass half-empty and in this section the authors propose a critical reflection on scarceness of novel targeted lupus therapies. They show how hard it is to identify suitable biological and clinical targets and to choose the patients that may best fit those targets, as well as to stratify patients according to disease subtype and response, all contributing to the final outcome. On the other hand, reasons are emerging to see the glass half-full, including the growing evidence that disease activity and damage can both be hindered by the proper use of novel drugs and that promising molecules are upcoming. In this section, the authors contextualize potentials and failures of new drugs, providing a critical reading of disappointing results and underlining the concrete benefits obtainable through a wise use of available treatments. Indeed, combining medications with new therapeutic strategies such as the treat-to-target seems the right approach to add some water to a filling glass.

Is PET/CT essential in the diagnosis and follow-up of temporal arteritis?
Publication date: November 2017
Source:Autoimmunity Reviews, Volume 16, Issue 11 Author(s): Carlo Salvarani, Alessandra Soriano, Francesco Muratore, Yehuda Shoenfeld, Daniel Blockmans The increasing availability and improvement of imaging techniques are deeply influencing diagnosis and work-up of patients affected with vasculitis, particularly those with large vessel vasculitis (LVV). Fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), especially when integrated with computed tomography (CT), is taking hold as a useful diagnostic technique to examine the aorta and the other large vessels in giant cell arteritis (GCA) with concomitant large vessel involvement (LV-GCA). In this paper we examined the progresses performed in this field in the last twenty years and the evidence available so far according to two different points of view (‘pros’ and ‘cons’), in order to give a comprehensive answer to a still open question about the role of PET/CT in the diagnosis and follow-up of GCA.
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