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
TLDR
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.Abstract:
Systemic lupus erythematosus (SLE) is a complex, inflammatory autoimmune disease that affects multiple organ systems. We used global gene expression profiling of peripheral blood mononuclear cells to identify distinct patterns of gene expression that distinguish most SLE patients from healthy controls. Strikingly, about half of the patients studied showed dysregulated expression of genes in the IFN pathway. Furthermore, this IFN gene expression “signature” served as a marker for more severe disease involving the kidneys, hematopoetic cells, and/or the central nervous system. These results provide insights into the genetic pathways underlying SLE, and identify a subgroup of patients who may benefit from therapies targeting the IFN pathway.read more
Citations
More filters
Journal ArticleDOI
Systemic lupus erythematosus
Jessica J Manson,Anisur Rahman +1 more
TL;DR: Systemic lupus erythematosus is a relapsing and remitting disease, and treatment aims are threefold: managing acute periods of potentially life-threatening ill health, minimizing the risk of flares during periods of relative stability, and controlling the less life- threatening, but often incapacitating day to day symptoms.
Journal ArticleDOI
Interferon-γ: an overview of signals, mechanisms and functions
TL;DR: The current understanding of IFN‐γ ligand, receptor, ignal transduction, and cellular effects with a focus on macrophage responses and to a lesser extent, responses from other cell types that influence macrophages function during infection are reviewed.
Journal ArticleDOI
Plasmacytoid dendritic cells in immunity.
TL;DR: Recent progress on the characterization of plasmacytoid dendritic cell origin, development, migration and function in immunity and tolerance, as well as their effect on human diseases are reviewed.
Journal ArticleDOI
IPC: professional type 1 interferon-producing cells and plasmacytoid dendritic cell precursors.
TL;DR: After more than two decades of effort by researchers, IPCs finally claim their place in the hematopoietic chart as the most important cell type in antiviral innate immunity.
Journal ArticleDOI
Systematic identification of trans eQTLs as putative drivers of known disease associations
Harm-Jan Westra,Marjolein J. Peters,Tõnu Esko,Hanieh Yaghootkar,Claudia Schurmann,Johannes Kettunen,Mark W. Christiansen,Benjamin P. Fairfax,Katharina Schramm,Joseph E. Powell,Alexandra Zhernakova,Daria V. Zhernakova,Jan H. Veldink,Leonard H. van den Berg,Juha Karjalainen,Sebo Withoff,André G. Uitterlinden,Albert Hofman,Fernando Rivadeneira,Peter A C 't Hoen,Eva Reinmaa,Krista Fischer,Mari Nelis,Lili Milani,David Melzer,Luigi Ferrucci,Andrew B. Singleton,Dena G. Hernandez,Mike A. Nalls,Georg Homuth,Matthias Nauck,Dörte Radke,Uwe Völker,Markus Perola,Veikko Salomaa,Jennifer A. Brody,Astrid Suchy-Dicey,Sina A. Gharib,Daniel A. Enquobahrie,Thomas Lumley,Grant W. Montgomery,Seiko Makino,Holger Prokisch,Christian Herder,Michael Roden,Harald Grallert,Thomas Meitinger,Konstantin Strauch,Yang Li,Ritsert C. Jansen,Peter M. Visscher,Julian C. Knight,Bruce M. Psaty,Samuli Ripatti,Samuli Ripatti,Samuli Ripatti,Alexander Teumer,Timothy M. Frayling,Andres Metspalu,Joyce B. J. van Meurs,Lude Franke +60 more
TL;DR: Variants associated with cholesterol metabolism and type 1 diabetes showed similar phenomena, indicating that large-scale eQTL mapping provides insight into the downstream effects of many trait-associated variants.
References
More filters
Journal ArticleDOI
Cluster analysis and display of genome-wide expression patterns
TL;DR: A system of cluster analysis for genome-wide expression data from DNA microarray hybridization is described that uses standard statistical algorithms to arrange genes according to similarity in pattern of gene expression, finding in the budding yeast Saccharomyces cerevisiae that clustering gene expression data groups together efficiently genes of known similar function.
Journal ArticleDOI
Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
TL;DR: In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries, and the presence and clinical associations or antiphospholipid antibodies in patients with SLE was suggested.
Journal ArticleDOI
A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group.
Stephan R. Targan,Stephen B. Hanauer,S. J. H. Van Deventer,Lloyd Mayer,Daniel H. Present,T. Braakman,K. L. Dewoody,T. F. Schaible,Paul Rutgeerts +8 more
TL;DR: A 12-week multicenter, double-blind, placebo-controlled trial of cA2 in 108 patients with moderate-to-severe Crohn's disease that was resistant to treatment, finding clinical response, the primary end point, was a reduction of 70 or more points in the score on theCrohn's Disease Activity Index at four weeks.
Journal ArticleDOI
Exploring the new world of the genome with DNA microarrays
Patrick O. Brown,David Botstein +1 more
TL;DR: Exploration of the genome using DNA microarrays and other genome–scale technologies should narrow the gap in the knowledge of gene function and molecular biology between the currently–favoured model organisms and other species.
Journal ArticleDOI
Identification of genes differentially regulated by interferon α, β, or γ using oligonucleotide arrays
TL;DR: The results demonstrate the usefulness of oligonucleotide arrays in monitoring mammalian gene expression on a broad and unprecedented scale and provide insights into the basic mechanisms of IFN actions.