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https://www.readbyqxmd.com/read/29229575/anti-melanoma-differentiation-associated-gene-5-mda5-dermatomyositis-a-concise-review-with-an-emphasis-on-distinctive-clinical-features
#1
REVIEW
Drew Jb Kurtzman, Ruth Ann Vleugels
Melanoma differentiation-associated gene 5 (MDA5) is a recently described autoantigen target in a subset of patients with dermatomyositis (DM). Anti-MDA5 DM is characterized by a unique mucocutaneous and systemic phenotype that includes cutaneous and oral ulceration, painful palmar papules, alopecia, panniculitis, arthritis, a lower incidence of myositis, and, importantly, an elevated risk of interstitial lung disease, with a potentially fatal course. Because the clinical features may differ substantially from those typically observed in cutaneous DM, the diagnosis is often overlooked, which may negatively affect patient outcomes...
December 8, 2017: Journal of the American Academy of Dermatology
https://www.readbyqxmd.com/read/29225988/effective-administration-of-rituximab-in-anti-mda5-antibody-positive-dermatomyositis-with-rapidly-progressive-interstitial-lung-disease-and-refractory-cutaneous-involvement-a-case-report-and-literature-review
#2
Yuka Ogawa, Dai Kishida, Yasuhiro Shimojima, Koichi Hayashi, Yoshiki Sekijima
We describe the case of a 48-year-old man with dermatomyositis (DM) who demonstrated rapidly progressive interstitial lung disease (RP-ILD) and refractory cutaneous involvement together with high levels of anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5-Ab). Even after combination immunosuppressive therapy including a corticosteroid, cyclosporine A, and intravenous cyclophosphamide, his respiratory insufficiency and cutaneous involvement progressively worsened. However, the administration of rituximab (RTX) resulted in clinical remission as well as a visible reduction in anti-MDA5-Ab levels, suggesting that RTX could be a useful remedy in cases refractory to conventional immunosuppressive agents, especially those of RP-ILD related to anti-MDA5-Ab-positive DM...
2017: Case Reports in Rheumatology
https://www.readbyqxmd.com/read/29203516/alternative-splicing-transcripts-of-zebrafish-lgp2-gene-differentially-contribute-to-ifn-antiviral-response
#3
Qi-Min Zhang, Xiang Zhao, Zhi Li, Min Wu, Jian-Fang Gui, Yi-Bing Zhang
In mammals, RIG-I like receptors (RLRs) RIG-I and melanoma differentiation-associated gene 5 (MDA5) sense cytosolic viral RNA, leading to IFN antiviral response; however, LGP2 exhibits controversial functions. The same happens to fish LGP2. In this study we report that three zebrafish LGP2 splicing transcripts, a full-length LGP2, and two truncating variants, LGP2v1 and LGP2v2, play distinct roles during IFN antiviral response. Overexpression of the full-length LGP2 not only potentiates IFN response through the RLR pathway, in the absence or presence of poly(I:C) at limited concentrations, but also inhibits IFN response by relative high concentrations of poly(I:C) through functional attenuation of signaling factors involved in the RLR pathway; however, LGP2v1 and LGP2v2 only retain the inhibitory role...
December 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29194722/the-rna-genome-of-hepatitis-e-virus-robustly-triggers-antiviral-interferon-response
#4
Wenshi Wang, Yijin Wang, Changbo Qu, Shan Wang, Jianhua Zhou, Wanlu Cao, Lei Xu, Buyun Ma, Mohamad S Hakim, Yuebang Yin, Tiancheng Li, Maikel P Peppelenbosch, Jingmin Zhao, Qiuwei Pan
The outcomes of hepatitis E virus (HEV) infection are diverse, ranging from asymptomatic carrier, self-limiting acute infection, fulminant hepatitis to persistent infection. This is closely associated with the immunological status of the host. This study aims to understand the innate cellular immunity as the first-line defense mechanisms in response to HEV infection. Phosphorylation of STAT1, a hallmark of the activation of antiviral interferon (IFN) response, was observed in the liver tissues of majority of HEV infected patients, but not in the liver of uninfected individuals...
December 1, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29186193/rig-i-like-receptor-activation-by-dengue-virus-drives-follicular-t-helper-cell-formation-and-antibody-production
#5
Joris K Sprokholt, Tanja M Kaptein, John L van Hamme, Ronald J Overmars, Sonja I Gringhuis, Teunis B H Geijtenbeek
Follicular T helper cells (TFH) are fundamental in orchestrating effective antibody-mediated responses critical for immunity against viral infections and effective vaccines. However, it is unclear how virus infection leads to TFH induction. We here show that dengue virus (DENV) infection of human dendritic cells (DCs) drives TFH formation via crosstalk of RIG-I-like receptor (RLR) RIG-I and MDA5 with type I Interferon (IFN) signaling. DENV infection leads to RLR-dependent IKKε activation, which phosphorylates IFNα/β receptor-induced STAT1 to drive IL-27 production via the transcriptional complex ISGF3...
November 29, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29166644/cylindromatosis-cyld-a-deubiquitinase-attenuates-inflammatory-signaling-pathways-by-activating-toll-like-receptor-3-in-human-mesangial-cells
#6
Tadaatsu Imaizumi, Ryo Hayakari, Shojiro Watanabe, Tomomi Aizawa, Tomoh Matsumiya, Hidemi Yoshida, Kazushi Tsuruga, Shogo Kawaguchi, Hiroshi Tanaka
BACKGROUND/AIMS: Cylindromatosis (CYLD), a deubiquitinase, negatively regulates nuclear factor-κB in various cells. However, its potential roles in glomerular inflammation remain unclear. Because the activation of the Toll-like receptor 3 (TLR3)/type I interferon (IFN) pathways plays a pivotal role in chronic kidney diseases (CKD), we examined the role of CYLD in the TLR3 signaling in cultured human mesangial cells (MCs). METHODS: We stimulated CYLD-silenced MCs with polyinosinic-polycytidylic acid (poly IC), a synthetic analogue of dsRNA, and studied representative TLR3/IFN-β pathways (i...
November 22, 2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/29162227/anti-mda5-positive-dermatomyositis-a-description-of-the-cutaneous-and-systemic-manifestations-in-2-cases
#7
N Barrientos, J J Sicilia, M J Moreno de Vega, J D Dominguez
No abstract text is available yet for this article.
November 18, 2017: Actas Dermo-sifiliográficas
https://www.readbyqxmd.com/read/29137638/virus-triggered-exacerbation-in-allergic-asthmatic-children-neutrophilic-airway-inflammation-and-alteration-of-virus-sensors-characterize-a-subgroup-of-patients
#8
Antoine Deschildre, Muriel Pichavant, Ilka Engelmann, Carole Langlois, Elodie Drumez, Guillaume Pouessel, Sophie Boileau, David Romero-Cubero, Irina Decleyre-Badiu, Anny Dewilde, Didier Hober, Véronique Néve, Caroline Thumerelle, Stéphanie Lejeune, Clémence Mordacq, Philippe Gosset
BACKGROUND: Viruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function...
November 14, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29132350/avian-infectious-bronchitis-virus-disrupts-the-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-by-cleavage-of-the-adaptor-protein-mavs
#9
Liping Yu, Xiaorong Zhang, Tianqi Wu, Jin Su, Yuyang Wang, Yuexin Wang, Baoyang Ruan, Xiaosai Niu, Yantao Wu
BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection...
November 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29128691/type-i-interferon-mediated-autoinflammation-and-autoimmunity
#10
REVIEW
Stefanie Kretschmer, Min Ae Lee-Kirsch
The monogenic type I interferonopathies comprise a heterogenous group of disorders of the innate immune system associated with constitutive activation of antiviral type I interferon (IFN). Despite a remarkable phenotypic diversity, type I interferonopathies are commonly characterized by autoinflammation and varying degrees of autoimmunity or immunodeficiency. The elucidation of the underlying genetic causes has revealed novel cell-intrinsic mechanisms that protect the organism against inappropriate immune recognition of self nucleic acids by cytosolic sensors such as cGAS or MDA5 through metabolizing or processing of intracellular DNA or RNA...
November 9, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/29117565/the-e3%C3%A2-ubiquitin-ligase-trim40-attenuates-antiviral-immune-responses-by-targeting-mda5-and-rig-i
#11
Chunyuan Zhao, Mutian Jia, Hui Song, Zhongxia Yu, Wenwen Wang, Qi Li, Lining Zhang, Wei Zhao, Xuetao Cao
Retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including melanoma differentiation-associated gene 5 (MDA5) and RIG-I, are crucial for host recognition of non-self RNAs, especially viral RNA. Thus, the expression and activation of RLRs play fundamental roles in eliminating the invading RNA viruses and maintaining immune homeostasis. However, how RLR expression is tightly regulated remains to be further investigated. In this study, we identified a major histocompatibility complex (MHC)-encoded gene, tripartite interaction motif 40 (TRIM40), as a suppressor of RLR signaling by directly targeting MDA5 and RIG-I...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29106035/genetic-association-of-hla-drb1-multiple-polymorphisms-with-dermatomyositis-in-chinese-population
#12
Lin Jinming, Zhang Yongbiao, Qinglin Peng, Hanbo Yang, Jingli Shi, Mingliang Gu, Wenming Zhao, Guochun Wang
Genetic variation in human leukocyte antigen (HLA) plays an important role in the pathogenesis of dermatomyositis (DM). The aim of this study was to investigate the association of HLA class II with DM in China. 224 DM patients and 300 healthy controls were randomly enrolled at China-Japan Friendship Hospital. High resolution typing of HLA-DRB1 alleles was performed by sequencing based typing (SBT). The HLA-DQA1 and HLA-DQB1 alleles were determined by PCR sequence-specific primers (SSP). The frequencies of HLA-DRB1*09:01 (28...
November 6, 2017: HLA
https://www.readbyqxmd.com/read/29100916/molecular-characterization-ontogeny-and-expression-profiling-of-mitochondrial-antiviral-signaling-adapter-mavs-from-asian-seabass-lates-calcarifer-bloch-1790
#13
Rahul Krishnan, P Girish Babu, K Jeena, Gayathri Tripathi, Kurcheti Pani Prasad
Mitochondrial antiviral signaling protein (MAVS), an innate immune signaling adapter coordinates the signals received from two independent cytosolic pathogen recognition receptors (RIG-1 and MDA5) to induce antiviral genes. In the present study the MAVS gene of Lates calcarifer (LcMAVS) was cloned and characterized. The complete cDNA sequence of LcMAVS was 3160 bp and encodes a poly peptide of 577 amino acids. Structural analysis of LcMAVS revealed an N-terminal CARD-like domain, central proline-rich domain and a C-terminal transmembrane domain...
October 31, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29100298/assessment-of-anti-mda5-antibody-as-a-diagnostic-biomarker-in-patients-with-dermatomyositis-associated-interstitial-lung-disease-or-rapidly-progressive-interstitial-lung-disease
#14
Liubing Li, Qian Wang, Xiaoting Wen, Chenxi Liu, Chanyuan Wu, Funing Yang, Xiaofeng Zeng, Yongzhe Li
Anti-melanoma differentiation-associated protein 5 (MDA5) antibody have been found in dermatomyositis (DM)-associated interstitial lung disease (DM-ILD) and DM-associated rapidly progressive ILD (DM-RPILD). Due to the conflicting results regarding the association between anti-MDA5 antibody and DM-ILD or DM-RPILD and the diagnostic value of this antibody for DM-ILD and DM-RPILD, we performed this meta-analysis. A systematic search was performed to identify studies published to January 14, 2017. Sixteen publications with 491 DM with ILD versus 605 DM without ILD, as well as eighteen publications with 186 DM with RPILD and 790 DM without RPILD were included...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29093381/the-serum-ferritin-level-is-associated-with-the-treatment-responsivity-for-rapidly-progressive-interstitial-lung-disease-with-amyopathic-dermatomyositis-irrespective-of-the-anti-mda5-antibody-level-a-case-report
#15
Takeshi Osawa, Kozo Morimoto, Yuka Sasaki, Shuichi Matsuda, Kazunari Yamana, Ryozo Yano, Takashi Uchiyama, Hajime Goto
We herein report he case of a 61-year-old woman with rapidly progressive interstitial lung disease caused by clinically amyopathic dermatomyositis. Both the serum ferritin and anti-MDA5 antibody levels were elevated at the time of admission. Despite intensive treatment with corticosteroids, immunosuppressants, immunoglobulins and polymyxin B direct hemoperfusion, the patient died 75 days after symptom onset. Over the course of treatment, the anti-MDA5 antibody level continually decreased, while the serum ferritin level increased, suggesting that sequential measurements of the serum ferritin level might be useful for evaluating the treatment responsivity, irrespective of the anti-MDA5 antibody level...
November 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/29069650/dnajb1-hsp40-suppresses-melanoma-differentiation-associated-gene-5-mitochondrial-antiviral-signaling-protein-function-in-conjunction-with-hsp70
#16
Ken Takashima, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases...
October 26, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29065773/describing-and-expanding-the-clinical-phenotype-of-anti-mda5-associated-rapidly-progressive-interstitial-lung-disease-case-series-of-nine-canadian-patients-and-literature-review
#17
S Hoa, Y Troyanov, M J Fritzler, I N Targoff, S Chartrand, A M Mansour, E Rich, H Boudabbouz, J Bourré-Tessier, M Albert, J R Goulet, M Landry, J L Senécal
OBJECTIVE: To describe and expand the phenotype of anti-MDA5-associated rapidly progressive interstitial lung disease (MDA5-RPILD) in Canadian patients. METHOD: All proven cases of MDA5-RPILD hospitalized in the University of Montreal's affiliated centres from 2004 to 2015 were selected for inclusion. RESULTS: Of nine consecutive patients, RPILD was the presenting manifestation in seven, whereas two patients developed RPILD 2 years after the onset of arthritis and of chronic interstitial lung disease...
October 25, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29043891/rapidly-progressive-interstitial-lung-disease-in-a-patient-with-anti-mda5-positive-amyopathic-dermatomyositis
#18
A Nandy, S Gaïni, P Sore
No abstract text is available yet for this article.
October 18, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/29042669/rna-editing-by-adar1-regulates-innate-and-antiviral-immune-functions-in-primary-macrophages
#19
Maria Pujantell, Eva Riveira-Muñoz, Roger Badia, Marc Castellví, Edurne Garcia-Vidal, Guillem Sirera, Teresa Puig, Cristina Ramirez, Bonaventura Clotet, José A Esté, Ester Ballana
ADAR1-dependent A-to-I editing has recently been recognized as a key process for marking dsRNA as self, therefore, preventing innate immune activation and affecting the development and resolution of immune-mediated diseases and infections. Here, we have determined the role of ADAR1 as a regulator of innate immune activation and modifier of viral susceptibility in primary myeloid and lymphoid cells. We show that ADAR1 knockdown significantly enhanced interferon, cytokine and chemokine production in primary macrophages that function as antiviral paracrine factors, rendering them resistant to HIV-1 infection...
October 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29032405/agaricus-blazei-murill-polysaccharides-protect-against-cadmium-induced-oxidative-stress-and-inflammatory-damage-in-chicken-spleens
#20
Wanqiu Xie, Ai Lv, Ruyue Li, Zequn Tang, Dexing Ma, Xiaodan Huang, Ruili Zhang, Ming Ge
Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group...
October 14, 2017: Biological Trace Element Research
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