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https://www.readbyqxmd.com/read/28296211/deleterious-effects-of-nonsynonymous-single-nucleotide-variants-of-human-il-1%C3%AE-gene
#1
Yue-Hui Zhang, Jia Song, Jing Zhang, Jiang Shao
The IL-1β gene is currently topic of interest for its important role in the pathogenesis of intervertebral disc degeneration. The new sequencing technology makes it crucial to study the effects of variants in IL-1β. Thus, 714 IL-1β variants with evidence supporting were collected from the EMBL database. Among them, 62 were nonsynonymous single nucleotide variants (nsSNVs). Furthermore, six common nsSNVs were predicted to have damaging effects by SIFT, PolyPhen, PROVEAN and SNPs&GO. Based on the constructed three-dimensional structure of pro-IL-1β, rs375479974 with a mutation of Phe to Ser was proposed to reduce the stability of the pro-IL-1β protein...
March 15, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28288653/inflammatory-bowel-disease-following-anti-interleukin-1-treatment-in-systemic-juvenile-idiopathic-arthritis
#2
Boris Hügle, Fabian Speth, Johannes-Peter Haas
BACKGROUND: Inflammatory bowel disease can develop in the context of some rheumatic diseases in childhood, including juvenile idiopathic arthritis (JIA). Inflammatory bowel disease (IBD) is frequently associated with other immune-mediated diseases; however, systemic onset JIA (sJIA) has not previously been connected to IBD. Treatment of sJIA has significantly changed in recent years, possibly causing changes in inflammatory patterns. Therefore, data from the German Center for Pediatric and Adolescent Rheumtology from 2010 until 2015 were analyzed by retrospective chart review...
March 14, 2017: Pediatric Rheumatology Online Journal
https://www.readbyqxmd.com/read/28266235/canakinumab-for-first-line-steroid-free-treatment-in-a-child-with-systemic-onset-juvenile-idiopathic-arthritis
#3
G Horneff, J Peitz, J Kekow, D Foell
No abstract text is available yet for this article.
March 7, 2017: Scandinavian Journal of Rheumatology
https://www.readbyqxmd.com/read/28261211/targeting-the-monocyte-macrophage-lineage-in-solid-organ-transplantation
#4
REVIEW
Thierry P P van den Bosch, Nynke M Kannegieter, Dennis A Hesselink, Carla C Baan, Ajda T Rowshani
There is an unmet clinical need for immunotherapeutic strategies that specifically target the active immune cells participating in the process of rejection after solid organ transplantation. The monocyte-macrophage cell lineage is increasingly recognized as a major player in acute and chronic allograft immunopathology. The dominant presence of cells of this lineage in rejecting allograft tissue is associated with worse graft function and survival. Monocytes and macrophages contribute to alloimmunity via diverse pathways: antigen processing and presentation, costimulation, pro-inflammatory cytokine production, and tissue repair...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28191908/il-1beta-induces-thymic-stromal-lymphopoietin-and-an-atopic-dermatitis-like-phenotype-in-reconstructed-healthy-human-epidermis
#5
Marine Bernard, Cédric Carrasco, Léo Laoubi, Béatrice Guiraud, Aurore Rozières, Catherine Goujon, Hélène Duplan, Sandrine Bessou-Touya, Jean-François Nicolas, Marc Vocanson, Marie-Florence Galliano
Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and a marked TH 2 polarization. Recent studies suggest that IL-1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL-1β signalling on the epidermal homeostasis of both healthy subjects and AD patient [with functional filaggrin (FLG) alleles] with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL-1β promoted: (i) a robust secretion of TSLP in an NFkB-dependant manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex...
February 13, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28140549/treatment-options-for-pyoderma-gangrenosum
#6
REVIEW
Sven R Quist, Luise Kraas
Pyoderma gangrenosum (PG) is an orphan disease. While research on such disorders is based on only few randomized multicenter as well as retrospective studies, most of the data comes from case series of small patient groups. Apart from topical and intralesional therapeutic options for early stages and mild disease courses, treatment predominantly involves systemic therapeutic agents. Besides systemic corticosteroids and cyclosporine A (CsA), options also include intravenous immunoglobulins (IVIG) and biologics such as the TNFα inhibitors infliximab, adalimumab, and etanercept; the interleukin (IL) 12/23 antibody ustekinumab; the IL-1 receptor antagonist anakinra; and the IL-1β antibody canakinumab...
January 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28140542/therapieoptionen-beim-pyoderma-gangraenosum
#7
REVIEW
Sven R Quist, Luise Kraas
Das Pyoderma gangraenosum (PG) gehört zu den orphan diseases, deren Erforschung sich lediglich auf einzelne, randomisierte, multizentrische sowie retrospektive Studien stützen kann und überwiegend auf Fallserien an kleinen Patientenkollektiven beruht. Die Therapie basiert neben topischen und lokal intraläsionalen Therapieoptionen, bei initialem und leichtem Krankheitsverlauf, insbesondere auf der Gabe von Systemtherapeutika. Diese beinhaltet neben den systemischen Glukokortikosteroiden und Ciclosporin A (CsA) auch Biologika wie intravenöses Immunglobulin G (IVIG), die TNFα-Inhibitoren Infliximab, Adalimumab und Etanercept, den IL-12/23-Antikörper Ustekinumab, den Interleukin-1-Rezeptorantagonist Anakinra und den Interleukin-1β-Antikörper Canakinumab...
January 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28118536/csf-cytokines-correlate-with-aseptic-meningitis-and-blood-brain-barrier-function-in-neonatal-onset-multisystem-inflammatory-disease-nomid
#8
Jackeline Rodriguez-Smith, Yen-Chih Lin, Wanxia Li Tsai, Hanna Kim, Gina Montealegre-Sanchez, Dawn Chapelle, Yan Huang, Cailin H Sibley, Massimo Gadina, Robert Wesley, Bibiana Bielekova, Raphaela Goldbach-Mansky
OBJECTIVE: To evaluate proinflammatory cytokines and leukocyte subpopulations in cerebrospinal spinal fluid (CSF) and blood of NOMID patients post-treatment; and to compare inflammatory cytokines in CSF and blood in 6 patients treated with two IL-1 blockers, anakinra and canakinumab. METHODS: We immunophenotyped CSF on 17 anakinra-treated pediatric NOMID patients during routine follow-up visits between December 2011 and October 2013 and analyzed CSF cytokine levels in baseline and 3-5 years follow-up samples compared to healthy controls...
January 24, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28115015/early-changes-in-gene-expression-and-inflammatory-proteins-in-systemic-juvenile-idiopathic-arthritis-patients-on-canakinumab-therapy
#9
Arndt H Brachat, Alexei A Grom, Nico Wulffraat, Hermine I Brunner, Pierre Quartier, Riva Brik, Liza McCann, Huri Ozdogan, Lidia Rutkowska-Sak, Rayfel Schneider, Valeria Gerloni, Liora Harel, Maria Terreri, Kristin Houghton, Rik Joos, Daniel Kingsbury, Jorge M Lopez-Benitez, Stephan Bek, Martin Schumacher, Marie-Anne Valentin, Hermann Gram, Ken Abrams, Alberto Martini, Daniel J Lovell, Nanguneri R Nirmala, Nicolino Ruperto
BACKGROUND: Canakinumab is a human anti-interleukin-1β (IL-1β) monoclonal antibody neutralizing IL-1β-mediated pathways. We sought to characterize the molecular response to canakinumab and evaluate potential markers of response using samples from two pivotal trials in systemic juvenile idiopathic arthritis (SJIA). METHODS: Gene expression was measured in patients with febrile SJIA and in matched healthy controls by Affymetrix DNA microarrays. Transcriptional response was assessed by gene expression changes from baseline to day 3 using adapted JIA American College of Rheumatology (aACR) response criteria (50 aACR JIA)...
January 23, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28078079/looking-forward-to-new-targeted-treatments-for-chronic-spontaneous-urticaria
#10
REVIEW
Emek Kocatürk, Marcus Maurer, Martin Metz, Clive Grattan
The introduction of omalizumab to the management of chronic spontaneous urticaria (CSU) has markedly improved the therapeutic possibilities for both, patients and physicians dealing with this disabling disease. But there is still a hard core of patients who do not tolerate or benefit from existing therapies and who require effective treatment. Novel approaches include the use of currently available drugs off-licence, investigational drugs currently undergoing clinical trials and exploring the potential for therapies directed at pathophysiological targets in CSU...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/28042127/longterm-beneficial-effect-of-canakinumab-in-colchicine-resistant-familial-mediterranean-fever
#11
Katerina Laskari, Panagiota Boura, George N Dalekos, Alexandros Garyfallos, Dimitrios Karokis, Dimitrios Pikazis, Loukas Settas, Grigoris Skarantavos, Elena Tsitsami, Petros P Sfikakis
OBJECTIVE: To assess the efficacy and safety of the interleukin-1β (IL-1β) inhibitor canakinumab in all adolescent and adult patients with familial Mediterranean fever (FMF) identified from the Greek National Registry for off-label drug use between 2010 and 2015. METHODS: In this retrospective longitudinal outcome study, clinical and laboratory data were collected from 14 patients (7 men) aged median 38.5 years (range 13-70), with median disease duration of 14 years, and active FMF despite colchicine (n = 9) or both colchicine and anakinra (n = 5)...
January 2017: Journal of Rheumatology
https://www.readbyqxmd.com/read/27999545/il-1-inhibition-in-systemic-juvenile-idiopathic-arthritis
#12
REVIEW
Gabriella Giancane, Francesca Minoia, Sergio Davì, Giulia Bracciolini, Alessandro Consolaro, Angelo Ravelli
Systemic juvenile idiopathic arthritis (sJIA) is the form of childhood arthritis whose treatment is most challenging. The demonstration of the prominent involvement of interleukin (IL)-1 in disease pathogenesis has provided the rationale for the treatment with biologic medications that antagonize this cytokine. The three IL-1 blockers that have been tested so far (anakinra, canakinumab, and rilonacept) have all been proven effective and safe, although only canakinumab is currently approved for use in sJIA. The studies on IL-1 inhibition in sJIA published in the past few years suggest that children with fewer affected joints, higher neutrophil count, younger age at disease onset, shorter disease duration, or, possibly, higher ferritin level may respond better to anti-IL-1 treatment...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27984003/a-systematic-analysis-of-treatment-and-outcomes-of-nod2-associated-autoinflammatory-disease
#13
Qingping Yao, Bo Shen
OBJECTIVES: Yao syndrome, formerly named NOD2-associated autoinflammatory disease, is a periodic disease characterized by fever, dermatitis, polyarthritis/leg swelling, and gastrointestinal and sicca-like symptoms associated with specific NOD2 sequence variants. Our aim was to evaluate the treatment and outcomes of the disease. METHODS: A total of 52 adult patients with autoinflammatory disease phenotype were diagnosed with Yao syndrome and enrolled at the Cleveland Clinic between November 2009 and May 2015...
March 2017: American Journal of Medicine
https://www.readbyqxmd.com/read/27981463/interleukin-il-1-inhibition-with-anakinra-and-canakinumab-in-beh%C3%A3-et-s-disease-related-uveitis-a-multicenter-retrospective-observational-study
#14
Claudia Fabiani, Antonio Vitale, Giacomo Emmi, Giuseppe Lopalco, Lorenzo Vannozzi, Silvana Guerriero, Stefano Gentileschi, Daniela Bacherini, Rossella Franceschini, Bruno Frediani, Mauro Galeazzi, Florenzo Iannone, Gian Marco Tosi, Luca Cantarini
This study aimed to evaluate the role of interleukin (IL)-1 inhibitors anakinra (ANA) and canakinumab (CAN) in the treatment of Behçet's disease (BD)-related uveitis. Multicenter retrospective observational study includes 19 consecutive BD patients (31 affected eyes) received treatment with anti-IL-1 agents. Data were analyzed at baseline and at 3 and 12 months. The primary endpoint is the reduction of ocular inflammatory flares (OIF). The secondary endpoints are improvement of best corrected visual acuity (BCVA); reduction of macular thickness defined by optical coherence tomography (OCT) and of vasculitis identified with fluorescein angiography (FA); evaluation of statistically significant differences between patients treated with IL-1 inhibitors as monotherapy, subjects also administered with disease modifying anti-rheumatic drugs (DMARDs) and/or corticosteroids as well as between patients administered with IL-1 inhibitors as first line biologic treatment and those previously treated with TNF-α inhibitors...
January 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/27974104/long-term-safety-and-efficacy-of-canakinumab-in-cryopyrin-associated-periodic-syndrome-results-from-an-open-label-phase-iii-pivotal-study-in-japanese-patients
#15
Shumpei Yokota, Tomoyuki Imagawa, Ryuta Nishikomori, Hidetoshi Takada, Ken Abrams, Karine Lheritier, Toshio Heike, Toshiro Hara
OBJECTIVES: To assess the long-term safety and efficacy of canakinumab in Japanese patients with cryopyrin-associated periodic syndrome (CAPS). METHODS: In this open-label phase 3 study, Japanese patients aged ≥2 years with CAPS received canakinumab 2-8 mg/kg subcutaneously every 8 weeks. The duration of the core treatment phase was 24 weeks followed by 22 months extension phase. The primary objective was the proportion of patients free of clinical and serologic relapse at week 24...
December 14, 2016: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/27886801/approach-to-the-patients-with-inadequate-response-to-colchicine-in-familial-mediterranean-fever
#16
REVIEW
Ahmet Gül
Familial Mediterranean fever (FMF) is the most common form of monogenic autoinflammatory conditions, and response to colchicine has been considered as one of its distinctive features among other hereditary periodic fever disorders. Prophylactic colchicine has been shown to be effective in the prevention of inflammatory attacks and development of amyloidosis. However, the highest tolerable doses of colchicine may not be adequate enough to manage these goals in approximately 5% of FMF patients. Inadequate response to colchicine in fully compliant FMF patients may be associated with genetic and/or environmental factors affecting disease severity and colchicine bioavailability...
April 2016: Best Practice & Research. Clinical Rheumatology
https://www.readbyqxmd.com/read/27860302/clinical-and-genetic-association-radiological-findings-and-response-to-biological-therapy-in-seven-children-from-qatar-with-non-bacterial-osteomyelitis
#17
Taha Moussa, Venkatraman Bhat, Vishwanatha Kini, Basil M Fathalla
AIM: We aim to report the clinical manifestations, genetic testing results, magnetic resonance imaging (MRI) findings and biologics used in the management of non-bacterial osteomyelitis in our center. METHODS: We conducted a retrospective review of medical records. A previously proposed classification was implemented as follows: chronic recurrent multifocal osteomyelitis (CRMO), chronic non-bacterial osteomyelitis (CNBO) and acute non-bacterial osteomyelitis. RESULTS: Four females and three males with a median age at presentation of 6 years (6 months-14 years) presented with arthralgia (7/7), back pain (4/7), arthritis (4/7) and bone pain (2/7)...
November 9, 2016: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/27822185/a-snapshot-on-the-on-label-and-off-label-use-of-the-interleukin-1-inhibitors-in-italy-among-rheumatologists-and-pediatric-rheumatologists-a-nationwide-multi-center-retrospective-observational-study
#18
Antonio Vitale, Antonella Insalaco, Paolo Sfriso, Giuseppe Lopalco, Giacomo Emmi, Marco Cattalini, Raffaele Manna, Rolando Cimaz, Roberta Priori, Rosaria Talarico, Stefano Gentileschi, Ginevra de Marchi, Micol Frassi, Romina Gallizzi, Alessandra Soriano, Maria Alessio, Daniele Cammelli, Maria C Maggio, Renzo Marcolongo, Francesco La Torre, Claudia Fabiani, Serena Colafrancesco, Francesca Ricci, Paola Galozzi, Ombretta Viapiana, Elena Verrecchia, Manuela Pardeo, Lucia Cerrito, Elena Cavallaro, Alma N Olivieri, Giuseppe Paolazzi, Gianfranco Vitiello, Armin Maier, Elena Silvestri, Chiara Stagnaro, Guido Valesini, Marta Mosca, Salvatore de Vita, Angela Tincani, Giovanni Lapadula, Bruno Frediani, Fabrizio De Benedetti, Florenzo Iannone, Leonardo Punzi, Carlo Salvarani, Mauro Galeazzi, Donato Rigante, Luca Cantarini
Background: Interleukin (IL)-1 inhibitors have been suggested as possible therapeutic options in a large number of old and new clinical entities characterized by an IL-1 driven pathogenesis. Objectives: To perform a nationwide snapshot of the on-label and off-label use of anakinra (ANA) and canakinumab (CAN) for different conditions both in children and adults. Methods: We retrospectively collected demographic, clinical, and therapeutic data from both adult and pediatric patients treated with IL-1 inhibitors from January 2008 to July 2016...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27737744/arterial-effects-of-canakinumab-in-patients%C3%A2-with-atherosclerosis-and-type%C3%A2-2%C3%A2-diabetes-or-glucose-intolerance
#19
Robin P Choudhury, Jacqueline S Birks, Venkatesh Mani, Luca Biasiolli, Matthew D Robson, Philippe L L'Allier, Marc-Alexandre Gingras, Nadia Alie, Mary Ann McLaughlin, Craig T Basson, Alison D Schecter, Eric C Svensson, Yiming Zhang, Denise Yates, Jean-Claude Tardif, Zahi A Fayad
BACKGROUND: Evidence suggests that interleukin (IL)-1β is important in the pathogenesis of atherosclerosis and its complications and that inhibiting IL-1β may favorably affect vascular disease progression. OBJECTIVES: The goal of this study was to evaluate the effects of IL-1β inhibition with canakinumab versus placebo on arterial structure and function, determined by magnetic resonance imaging. METHODS: Patients (N = 189) with atherosclerotic disease and either type 2 diabetes mellitus or impaired glucose tolerance were randomized to receive placebo (n = 94) or canakinumab 150 mg monthly (n = 95) for 12 months...
October 18, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27715073/-schnitzlers-syndromedifferential-diagnostics-an-overview-of-therapeutic-options-and-description-of-5%C3%A2-cases-treated-with-anakinra
#20
Zdeněk Adam, Anna Šedivá, Renata Koukalová, Zdeněk Řehák, Hana Petrášová, Petr Szturz, Zdenka Adamová, Eva Vetešníková, Luděk Pour, Marta Krejčí, Viera Sandecká, Eva Pourová, Zdeňka Čermáková, Sabina Ševčíková, Zdeněk Král, Jiří Mayer
Schnitzlers syndrome is an acquired auto-inflammatory disease of still unclear origin. The Strasbourg criteria were adopted (non-infectious fever, chronic urticaria, changes in the bone structure, leukocytosis and higher values of inflammatory markers - CRP and presence of monoclonal immunoglobulin mostly of type IgM, very rarely of IgG) to establish this diagnosis. The first-choice therapy for this disease is the blocking of interleukin-1 effects. In practice, the interleukin-1 receptor antagonist, anakinra, is the most commonly used...
2016: Vnitr̆ní Lékar̆ství
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