Journal ArticleDOI
Gene-function studies in systemic lupus erythematosus
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Select examples of genes whose products have distinctly altered function in SLE and contribute to the pathogenic process are discussed and epigenetic modifications, which are abundantly present and might alter gene expression in the presence or absence of susceptibility variants, are considered.Abstract:
The aetiology of systemic lupus erythematosus (SLE) is complex and is known to involve both genetic and environmental factors. In a small number of patients, single-gene defects can lead to the development of SLE. Such genes include those encoding early components of the complement cascade and the 3'-5' DNA exonuclease TREX1. In addition, genome-wide association studies have identified single-nucleotide polymorphisms that confer some susceptibility to SLE. In this Review, we discuss selected examples of genes whose products have distinctly altered function in SLE and contribute to the pathogenic process. Specifically, we focus on the genes encoding integrin αM (ITGAM), IgG Fc receptors, sialic acid O-acetyl esterase (SIAE), the catalytic subunit of protein phosphatase PP2A (PPP2CA) and signalling lymphocytic activation molecule (SLAM) family members. Moreover, we highlight the changes in epigenetic signatures that occur in SLE. Such epigenetic modifications, which are abundantly present and might alter gene expression in the presence or absence of susceptibility variants, should be carefully considered when deconstructing the contribution of individual genes to the complex pathogenesis of SLE.read more
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Systemic Lupus Erythematosus
TL;DR: Contributions are gathered from physicians and researchers from North America, South America, Europe, and Asia that highlight several important and/or novel aspects of the molecular pathogenesis, clinical organ involvement, and experimental therapies in this prototypical systemic autoimmune disease.
Journal ArticleDOI
Systemic lupus erythematosus.
TL;DR: This Seminar reflects on changes in systemic lupus erythematosus classification criteria; considers aspects of its more serious clinical expression; and provides a brief review of its aetiopathogenesis, major complications, coping strategies, and conventional treatment.
Journal ArticleDOI
Genetics and pathogenesis of systemic lupus erythematosus and lupus nephritis
Chandra Mohan,Chaim Putterman +1 more
TL;DR: The genetic insights and molecular mechanisms for key pathogenic contributors in SLE and lupus nephritis are discussed, and the genes identified in human studies of SLE are categorized into one of four pathogenic events that lead to lupu nephitis.
Journal ArticleDOI
Pathogenesis of Human Systemic Lupus Erythematosus: A Cellular Perspective
Vaishali R. Moulton,Abel Suárez-Fueyo,Esra Meidan,Esra Meidan,Hao Li,Masayuki Mizui,George C. Tsokos +6 more
TL;DR: Novel observations have provided an improved understanding of the contribution of tissue-specific factors and associated damage, T and B lymphocytes, as well as innate immune cell subsets and their corresponding abnormalities.
Journal ArticleDOI
Intrinsic Self-DNA Triggers Inflammatory Disease Dependent on STING
TL;DR: It is demonstrated that phagocytes rather than myocytes are predominantly responsible for causing inflammation, an outcome that could be alleviated following adoptive transfer of normal bone marrow into TREX1−/− mice.
References
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Journal ArticleDOI
Homozygous C1q deficiency causes glomerulonephritis associated with multiple apoptotic bodies
Marina Botto,C Dell'Agnola,Anne E. Bygrave,EM Thompson,H.T. Cook,Franz Petry,Michael Loos,Pier Paolo Pandolfi,Mark Walport +8 more
TL;DR: The hypothesis that C1q deficiency causes autoimmunity by impairment of the clearance of apoptotic cells is compatible with the hypothesis that a physiological action of the early part of the classical pathway protects against the development of SLE.
Journal ArticleDOI
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
John B. Harley,John B. Harley,John B. Harley,Marta E. Alarcón-Riquelme,Lindsey A. Criswell,Chaim O. Jacob,Robert P. Kimberly,Kathy L. Moser,Kathy L. Moser,Betty P. Tsao,Timothy J. Vyse,Carl D. Langefeld,Swapan K. Nath,Joel M. Guthridge,Beth L. Cobb,Daniel B. Mirel,Miranda C. Marion,Adrienne H. Williams,Jasmin Divers,Wei Wang,Summer G. Frank,Bahram Namjou,Stacey Gabriel,Annette Lee,Peter K. Gregersen,Timothy W. Behrens,Timothy W. Behrens,Kimberly E. Taylor,Michelle M. A. Fernando,Raphael Zidovetzki,Patrick M. Gaffney,Patrick M. Gaffney,Jeffrey C. Edberg,John D. Rioux,Joshua O. Ojwang,Judith A. James,Joan T. Merrill,Gary S. Gilkeson,Michael F. Seldin,Hong Yin,Emily C. Baechler,Quan Zhen Li,Edward K. Wakeland,Gail R. Bruner,Kenneth M. Kaufman,Kenneth M. Kaufman,Jennifer A. Kelly +46 more
TL;DR: The results show that numerous genes, some with known immune-related functions, predispose to SLE, and evidence of association with replication is found at FCGR2A, PTPN22 and STAT4, regions previously associated with SLE and other autoimmune diseases.
Journal ArticleDOI
Trex1 Prevents Cell-Intrinsic Initiation of Autoimmunity
TL;DR: It is shown that single-stranded DNA derived from endogenous retroelements accumulates in Trex1-deficient cells, and thatTrex1 can metabolize reverse-transcribed DNA, and suggest an unanticipated contribution of endogenous Retroelements to autoimmunity.
Journal ArticleDOI
Association of systemic lupus erythematosus with C8orf13-BLK and ITGAM-ITGAX.
Geoffrey Hom,Robert R. Graham,Barmak Modrek,Kimberly E. Taylor,Ward Ortmann,Sophie Garnier,Annette Lee,Sharon A. Chung,Ricardo C. Ferreira,P. V. Krishna Pant,Dennis G. Ballinger,Roman Kosoy,F. Yesim Demirci,M. Ilyas Kamboh,Amy H. Kao,Chao Tian,Iva Gunnarsson,Anders A. Bengtsson,Solbritt Rantapää-Dahlqvist,Michelle Petri,Susan Manzi,Michael F. Seldin,Lars Rönnblom,Ann-Christine Syvänen,Lindsey A. Criswell,Peter K. Gregersen,Timothy W. Behrens +26 more
TL;DR: The authors identified and then confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region.
Journal ArticleDOI
A revised estimate of twin concordance in systemic lupus erythematosus
Dennis Deapen,Agustin Escalante,Lisa Weinrib,David A. Horwitz,Barbara Bachman,Pradip Roy-Burman,Ann Walker,Thomas M. Mack +7 more
TL;DR: MZ concordance for SLE is similar to that for other autoimmune diseases and is much lower than previously believed.
Related Papers (5)
Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus.
Spontaneous Autoimmune Disease in FcγRIIB-Deficient Mice Results from Strain-Specific Epistasis
Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
John B. Harley,John B. Harley,John B. Harley,Marta E. Alarcón-Riquelme,Lindsey A. Criswell,Chaim O. Jacob,Robert P. Kimberly,Kathy L. Moser,Kathy L. Moser,Betty P. Tsao,Timothy J. Vyse,Carl D. Langefeld,Swapan K. Nath,Joel M. Guthridge,Beth L. Cobb,Daniel B. Mirel,Miranda C. Marion,Adrienne H. Williams,Jasmin Divers,Wei Wang,Summer G. Frank,Bahram Namjou,Stacey Gabriel,Annette Lee,Peter K. Gregersen,Timothy W. Behrens,Timothy W. Behrens,Kimberly E. Taylor,Michelle M. A. Fernando,Raphael Zidovetzki,Patrick M. Gaffney,Patrick M. Gaffney,Jeffrey C. Edberg,John D. Rioux,Joshua O. Ojwang,Judith A. James,Joan T. Merrill,Gary S. Gilkeson,Michael F. Seldin,Hong Yin,Emily C. Baechler,Quan Zhen Li,Edward K. Wakeland,Gail R. Bruner,Kenneth M. Kaufman,Kenneth M. Kaufman,Jennifer A. Kelly +46 more