Are cytokines and chemokines suitable biomarkers for Takayasu arteritis?

Publication date: Available online 2 August 2017
Source:Autoimmunity Reviews
Author(s): Bruna Savioli, Wayel H. Abdulahad, Elisabeth Brouwer, Cees G.M. Kallenberg, Alexandre Wagner Silva de Souza
There is a growing need for disease related biomarkers in Takayasu arteritis (TA).The assessment of pro-inflammatory cytokines and chemokines in TA may provide a better understanding of its pathophysiology, and circulating levels of these mediators may act as biomarkers of disease activity. Serum level of interleukin 6 (IL-6) is a potential biomarker for TA, which is mostly associated with TA status and disease activity. Associations between TA and serum/plasma levels of other cytokines are less clear. mRNA expression of IL-4 and tumor necrosis factor α (TNFα) are constitutively increased in peripheral blood mononuclear cells (PBMC) from TA patients and the expression of both cytokines increases even more after PBMC stimulation in vitro, while the expression of IL-10 mRNA decreases. In addition, circulating T cells from TA patients produce increased levels of both Th1- and Th17-related cytokines upon in vitro stimulation. In the aorta from TA patients, an increased expression of interferon γ (IFNγ), IL-6, IL-12 and IL-17 has been described. Regarding circulating chemokines in TA, serum/plasma levels of IL-8 (CXCL8), CCL2 and CCL5 were shown to be elevated in TA patients compared with healthy controls as well as in TA patients with active disease compared with those in remission. Serum IL-6 seems to be the best biomarker for disease state and disease activity in TA and increased Th1 and Th17 responses are predominant in the pathophysiology of TA.



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The Yin and Yang of Regulatory T Cell and Therapy Progress in Autoimmune Disease

Publication date: Available online 2 August 2017
Source:Autoimmunity Reviews
Author(s): Yong-chao Qiao, Yan-hong Pan, Wei Ling, Fang Tian, Yin-ling Chen, Xiao-xi Zhang, Hai-lu Zhao
Autoimmune diseases (ADs) are primarily mediated by the failure of immunological self-tolerance. Regulatory T cells (Tregs) play a critical role in the maintenance of induced tolerance to peripheral self-antigens, suppressing immoderate immune responses deleterious to the host and preventing the ADs development. Tregs and suppressive cytokines are homeostatic with effective cells plus pro-inflammatory cytokines in healthy hosts which is defined as "Yang", and ADs are usually induced in case of disturbed homeostasis, which is defined as "Yin". Indeed, the Yin-Yang balance could explain the pathogenic mechanism of ADs. Tregs not only suppress CD4⁺ and CD8⁺ T cells but also can suppress other immune cells such as B cell, natural killer cell, DC and other antigen-presenting cell through cell-cell contact or secreting suppressive cytokines. In Tregs, Foxp3 as an intracellular protein displays a more specific marker than currently used other cell-surface markers (such as CD25, CD40L, CTLA-4, ICOS and GITR) in defining the naturally occurring CD4⁺ Tregs. Though the precise mechanism for the opposite effects of Tregs has not been fully elucidated, the importance of Tregs in ADs has been proved to be associated with kinds of immunocytes. At present, the surface marker, frequency and function of Tregs existed conflicts and hence the Tregs therapy in ADs faces challenges. Though some success has been achieved with Tregs therapy in few ADs both in murine models and humans, more effort should paid to meet the future challenges. This review summarizes the progress and discusses the phenotypic, numeric and functional abnormalities of Tregs and is the first time to systematically review the progress of Tregs therapy in kinds of ADs.



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Targeting interleukin-6 in autoimmune uveitis

Publication date: Available online 2 August 2017
Source:Autoimmunity Reviews
Author(s): Marina Mesquida, Blanca Molins, Víctor Llorenç, Maite Sáinz de la Maza, Alfredo Adán
Interleukin-6 (IL-6) is a key cytokine that is strongly up-regulated during infection and inflammation. Featuring pleiotropic activity, IL-6 is responsible for the induction of hepatic acute-phase proteins, trafficking of acute and chronic inflammatory cells, differentiation of adaptive T cell responses, homeostatic regulation, and tissue regeneration. Dysregulated IL-6 production has been associated with the development of a wide variety of systemic immune-mediated, chronic diseases, and even certain types of cancer. From the ocular perspective, significant elevation of IL-6 has been found in ocular fluids derived from diabetic macular edema, retinal vein occlusion, and refractory/chronic uveitis patients. During the last decade, tocilizumab, a neutralizing monoclonal antibody (mAb) that targets the IL-6 receptor (IL-6R), has been approved for the treatment of rheumatoid arthritis in >100 countries worldwide. Furthermore, it has been reported to be effective for the treatment of a number of autoimmune diseases including uveitis and its associated macular edema. Currently numerous candidate molecular strategies targeting the IL-6 signalling pathways are in progress through clinical trials in various disorders. Herein we discuss the basic biology of IL-6 and its pathological role in the development of immune-mediated conditions, particularly focusing on inflammatory eye diseases. It also provides an overview of the on-going clinical trials with the new anti-IL-6 mAbs and their potential use in the clinical practice.



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Fetal sequential multiorgan autoimmunity associated with recurrent post thymectomy thymoma

Publication date: Available online 2 August 2017
Source:Autoimmunity Reviews
Author(s): Ze-Hu Liu, Jun-Zhu Xu, Hong Shen




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How I treat idiopathic patients with inflammatory myopathies in the clinical practice

Publication date: Available online 2 August 2017
Source:Autoimmunity Reviews
Author(s): Lorenzo Cavagna, Sara Monti, Roberto Caporali, Mariele Gatto, Luca Iaccarino, Andrea Doria
Management of patients with idiopathic inflammatory myopathies (IIMs) is challenging given the systemic nature of the disease, which is often complicated by potentially life-threatening manifestations and the lack of standardized treatment regimens. Aim of this review is to provide the currently available evidence for immunotherapy in the treatment of various manifestations of IIM in order to help clinicians in the daily management of these patients.



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Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews

There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma.

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Association of Ugrp2 gene polymorphisms with adenoid hypertrophy in the pediatric population

Publication date: Available online 1 August 2017
Source:Brazilian Journal of Otorhinolaryngology
Author(s): Huntürk Atilla, Sibel Özdaş, Talih Özdaş, Sibel Baştimur, Sami Engin Muz, Işılay Öz, Kenan Kurt, Afife İzbirak, Mehmet Ali Babademez, Nilgün Vatandaş
IntroductionAdenoid hypertrophy (AH) is a condition that presents itself as the chronic enlargement of adenoid tissues; it is frequently observed in the pediatric population. The Ugrp2 gene, a member of the secretoglobin superfamily, encodes a low-molecular weight protein that functions in the differentiation of upper airway epithelial cells. However, little is known about the association of Ugrp2 genetic variations with AH.ObjectiveThe aim of this study is to investigate the association of single nucleotide polymorphisms (SNPs) in the Ugrp2 gene with AH and its related phenotypes.MethodsA total of 219 children, comprising 114 patients suffering from AH and 105 healthy patients without AH, were enrolled in this study. Genotypes of the Ugrp2 gene were determined by DNA sequencing.ResultsWe identified four SNPs (IVS1-189G>A, IVS1-89T>G, c.201delC, and IVS2-15G>A) in the Ugrp2 gene. Our genotype analysis showed that the Ugrp2 (IVS1-89T>G) TG and (c.201delC) CdelC genotypes and their minor alleles were associated with a considerable increase in the risk of AH compared with the controls (p=0.012, p=0.009, p=0.013, and p=0.037, respectively). Furthermore, Ugrp2 (GTdelCG, GTdelCA) haplotypes were significantly associated with AH (four SNPs ordered from 5′ to 3′; p=0.0001). SNP–SNP interaction analysis indicated a strong interaction between combined genotypes of the Ugrp2 gene contributing to AH, as well as an increased chance of diagnosis of AH (p<0.0001). In addition, diplotypes carrying the mutant Ugrp2 (c.201delC) allele were strongly associated with an increased risk of AH with asthma and AH with allergies (p=0.003 and p=0.0007, respectively).ConclusionSome SNPs and their combinations in the Ugrp2 gene are associated with an increased risk of developing AH. Therefore, we tried to underline the importance of genetic factors associated with AH and AH-related clinical phenotypes.



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