Journal ArticleDOI
The interferon signature in autoimmune diseases.
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TLDR
The observed IFN signature in several autoimmune diseases is a biomarker of active disease and is investigated as a tool when selecting treatment for individual patients.Abstract:
Purpose of reviewAn increased expression of type I interferon (IFN) regulated genes (an IFN signature) has been reported in blood and tissue cells from patients with SLE and other autoimmune diseases. We review the possible mechanisms behind the IFN signature as well as clinical and therapeutic consread more
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Journal ArticleDOI
Role of CD14+ monocyte-derived oxidised mitochondrial DNA in the inflammatory interferon type 1 signature in juvenile dermatomyositis
Meredyth G. Ll Wilkinson,Dale Moulding,Thomas McDonnell,Michael Orford,Chris Wincup,Joanna Ting,G. Otto,Restuadi Restuadi,Daniel Kelberman,Charalampia Papadopoulou,S. Castellano,Simon Eaton,Claire T Deakin,Elizabeth C. Rosser,Lucy R. Wedderburn +14 more
TL;DR: In this article , the host mechanisms contributing to the pathological interferon (IFN) type 1 signature in Juvenile dermatomyositis (JDM) were defined, and RNA-sequencing was performed on CD4+, CD8+, CD14+ and CD19+ cells sorted from pretreatment and on-treatment JDM (pretreatment n=10, ontreatment n=11) and age/sex matched child healthy-control (CHC n=4) peripheral blood mononuclear cell (PBMC).
Posted ContentDOI
High dose IFN-β activates GAF to enhance expression of ISGF3 target genes in epithelial cells
Kensei Kishimoto,Catera Wilder,Justin Buchanan,Minh Nguyen,Chidera Okeke,Chidera Okeke,Alexander Hoffmann,Quen J. Cheng +7 more
TL;DR: GAF is transcriptionally inactive in epithelial cells but enhances expression of ISGF3 target genes, thus functioning as a dose-sensitive amplifier of the IFN-β response.
Patent
Cgas in systemic lupus erythematosus (sle)
TL;DR: In this article, the authors presented therapeutic strategies for treatment of severe debilitating diseases associated with IFN-I due to cGAS activation, such as Crohn's disease, Crohn disease, and cancer.
Posted ContentDOI
A systems immunology approach identifies cytokine-induced STAT signaling pathways critical to rheumatoid arthritis disease activity and treatment response
Jason Ptacek,Rachael E. Hawtin,Dongmei Sun,Brent Louie,Erik Evensen,Barbara B. Mittleman,Alessandra Cesano,Guy Cavet,Clifton O. Bingham,Stacey S. Cofield,Jeffrey R. Curtis,Maria I. Danila,Chander Raman,Richard Furie,Mark C. Genovese,William H. Robinson,Marc C. Levesque,Larry W. Moreland,Peter A. Nigrovic,Nancy A. Shadick,James R. O'Dell,Geoffrey M. Thiele,E. William St. Clair,Christopher C. Striebich,Matthew Hale,Houman Khalili,Franak Batliwalla,Cynthia Aranow,Meggan Mackay,Betty Diamond,Garry P. Nolan,Peter K. Gregersen,S. Louis Bridges +32 more
TL;DR: This study provides novel information on RA disease mechanisms and serves as a framework for the discovery and validation of biomarkers of treatment response in RA.
Journal ArticleDOI
Metabolic Reprogramming of Innate Immune Cells as a Possible Source of New Therapeutic Approaches in Autoimmunity
Leila Mohammadnezhad,Mojtaba Shekarkar Azgomi,Marco Pio La Manna,Guido Sireci,Chiara Rizzo,Giusto Davide Badami,Bartolo Tamburini,Francesco Dieli,Giuliana Guggino,Nadia Caccamo +9 more
TL;DR: The effects of metabolic changes in autoimmune diseases, exerted by the leading actors of innate immunity, and their role in autoimmunity pathogenesis are discussed, suggesting many immunotherapeutic approaches.
References
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Journal ArticleDOI
Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus
Emily C. Baechler,Franak Batliwalla,George Karypis,Patrick M. Gaffney,Ward A. Ortmann,Karl J. Espe,Katherine B. Shark,William J. Grande,Karis M. Hughes,Vivek Kapur,Peter K. Gregersen,Timothy W. Behrens +11 more
TL;DR: Global gene expression profiling of peripheral blood mononuclear cells is used to identify distinct patterns of gene expression that distinguish most SLE patients from healthy controls, and identify a subgroup of patients who may benefit from therapies targeting the IFN pathway.
Journal ArticleDOI
Interferon and Granulopoiesis Signatures in Systemic Lupus Erythematosus Blood
Lynda Bennett,A. Karolina Palucka,Edsel Arce,Edsel Arce,Victoria Cantrell,Victoria Cantrell,Josef Borvak,Jacques Banchereau,Virginia Pascual,Virginia Pascual +9 more
TL;DR: Microarray analysis of blood cells reveals that immature granulocytes may be involved in SLE pathogenesis, and the IFN signature confirms the central role of this cytokine in Sle, using oligonucleotide microarrays.
Journal ArticleDOI
Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide.
Roberto Lande,Josh Gregorio,Valeria Facchinetti,Bithi Chatterjee,Bithi Chatterjee,Yi Hong Wang,Bernhard Homey,Wei Cao,Yui-Hsi Wang,Bing Su,Frank O. Nestle,Tomasz Zal,Ira Mellman,Ira Mellman,Jens-Michael Schröder,Yong-Jun Liu,Michel Gilliet +16 more
TL;DR: The data uncover a fundamental role of an endogenous antimicrobial peptide in breaking innate tolerance to self-DNA and suggest that this pathway may drive autoimmunity in psoriasis.
Journal ArticleDOI
JAK and STAT Signaling Molecules in Immunoregulation and Immune-Mediated Disease
TL;DR: Not only have genome-wide association studies demonstrated that this pathway is highly relevant to human autoimmunity, but targeting JAKs is now a reality in immune-mediated disease.
Journal ArticleDOI
Polymorphisms in the Tyrosine Kinase 2 and Interferon Regulatory Factor 5 Genes Are Associated with Systemic Lupus Erythematosus
Snaevar Sigurdsson,Gunnel Nordmark,Harald H H Göring,Katarina Lindroos,Ann-Christin Wiman,Gunnar Sturfelt,Andreas Jönsen,Solbritt Rantapää-Dahlqvist,Bozena Möller,Juha Kere,Sari Koskenmies,Elisabeth Widen,Maija-Leena Eloranta,Heikki Julkunen,Helga Kristjansdottir,Kristjan Steinsson,Gunnar V. Alm,Lars Rönnblom,Ann-Christine Syvänen +18 more
TL;DR: The results support a disease mechanism in SLE that involves key components of the type I IFN system, and identify SNPs that displayed strong signals in joint analysis of linkage and association with SLE.