The genetics and molecular pathogenesis of systemic lupus erythematosus (SLE) in populations of different ancestry

Goulielmos, George N.; Zervou, Maria I.; Vazgiourakis, Vassilios; Ghodke‐Puranik, Yogita; Garyfallos, Alexandros; Niewold, Timothy B.

doi:10.1016/j.gene.2018.05.041

Cited by 116 publications

(89 citation statements)

References 187 publications

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“…However, aberrant responses of NA sensors to self-NAs appear to play a central role in the pathogenic processes of SLE. GWAS have shown that SLE is associated with various genes encoding NA sensors and signaling molecules involved in signaling through NA sensors [39,40]. Moreover, mice deficient in various genes involved in NA metabolism develop lupus-like disease [41].…”

Section: Cd72 Recognizes the Lupus Self-antigen Sm/rnp As A Specificmentioning

confidence: 99%

Inhibitory B cell co-receptors and autoimmune diseases

Tsubata

2019

Immunological Medicine

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B cells express various inhibitory co-receptors including CD22 (also known as Siglec-2), Siglec-10 (Siglec-G in mice), CD72, LILRB (PIR-B in mice) and FccRIIB that contain immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region and negatively regulate BCR signaling by recruiting phosphatases to the ITIMs. Some of the inhibitory B cell co-receptors suppress development of SLE. Among these, CD72 most strongly regulates SLE. CD72 recognizes Sm/RNP, a lupus self-antigen and an endogenous TLR7 ligand, as a specific ligand, and suppresses B cell response to this TLR7 ligand. This suppression may inhibit development of SLE because TLR7 is indispensable in multiple mouse SLE models. In contrast, inhibitory B cell co-receptors such as CD22 and CD72 inhibit expansion of regulatory B cells that are known to regulate development of autoimmune diseases including type 1 diabetes (T1D) and multiple sclerosis. CD72 strongly exacerbate development of T1D in NOD mice probably by limiting expansion of regulatory B cells. Thus, inhibitory B cell co-receptors especially CD72 regulates distinct autoimmune diseases either positively or negatively. As B cell depletion therapy clearly reveals crucial roles of B cells in the regulation of various autoimmune diseases, CD72 may be a novel therapeutic target for treatment of autoimmune diseases.

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Section: Cd72 Recognizes the Lupus Self-antigen Sm/rnp As A Specificmentioning

confidence: 99%

Inhibitory B cell co-receptors and autoimmune diseases

Tsubata

2019

Immunological Medicine

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“…18 Considering ITGAM, it has been reported that the A-allele of ITGAM rs1145679 is associated with an increased susceptibility for the development of SLE in European, African, and Hispanic populations. 22 Other genes described are the ones encoding the tumor necrosis factor (ligand) superfamily, member 4 (TNFSF4) and its receptor, IL-10, interleukin-1 receptor-associated kinase 1 (IRAK1). The TNF receptor-associated factor 6 (TRAF6), which is involved in the activation of NF-kB (nuclear factorkappa B), has been associated with an increased susceptibility for both RA and SLE development.…”

Section: Genetic Factorsmentioning

confidence: 99%

“…The TNF receptor-associated factor 6 (TRAF6), which is involved in the activation of NF-kB (nuclear factorkappa B), has been associated with an increased susceptibility for both RA and SLE development. 22 A recent meta-analysis, developed by Jeong and colleagues, identified several genes that were confirmed regarding their association with SLE by using GWAS technique. An important amount of genes identified was associated with the interferon signaling pathway that is involved in the breaking of self-tolerance by the activation of antigen-presenting cells as an answer to autoantigens.…”

Section: Genetic Factorsmentioning

confidence: 99%

Rheumatoid arthritis and systemic lupus erythematosus: Pathophysiological mechanisms related to innate immune system

et al. 2019

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Rheumatoid arthritis and systemic lupus erythematosus are two highly prevalent autoimmune diseases that generate disability and low quality of life. The innate immune system, a long-forgotten issue in autoimmune diseases, is becoming increasingly important and represents a new focus for the treatment of these entities. This review highlights the role that innate immune system plays in the pathophysiology of rheumatoid arthritis and systemic lupus erythematosus. The role of the innate immune system in rheumatoid arthritis and systemic lupus erythematosus pathophysiology is not only important in early stages but is essential to maintain the immune response and to allow disease progression. In rheumatoid arthritis, genetic and environmental factors are involved in the initial stimulation of the innate immune response in which macrophages are the main participants, as well as fibroblast-like synoviocytes. In systemic lupus erythematosus, all the cells contribute to the inflammatory response, but the complement system is the major effector of the inflammatory process. Detecting alterations in the normal function of these cells, besides its contribution to the understanding of the pathophysiology of autoimmune diseases, could help to establish new treatment strategies for these diseases.

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“…Genome Wide Association Study (GWAS) is a powerful method, used to identify genetic risk factors in numerous diseases such as Asthma [32], Allergy [33], Multiple sclerosis (MS) [34], Systemic Lupus Erythematosus (SLE) [35], Rheumatoid Arthritis (RA) [36] and Systemic Sclerosis (Ssc) [37]. The goal of GWAS is to identify these genetic risk factors in order to make predictions about who is at risk and investigate the biological process of disease susceptibility for developing new prevention and treatment strategies.…”

Section: Genome Wide Association Studymentioning

confidence: 99%

Identification of candidate genes involved in Mercury Toxicokinetics and Mercury Induced Autoimmunity

Alkaissi¹

2018

Linköping University Medical Dissertations

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BACKGROUND: Autoimmune diseases require the involvement and activation of immune cells and occur when the body builds up an immune response against its own tissues. This process takes place due to the inability to distinguish self-antigen from foreign antigen. Systemic autoimmunity represents an important cause of morbidity and mortality in humans. The mechanisms triggering autoimmune responses are complex and involve a network of genetic factors. Genome wide association study (GWAS) is a powerful method, used to identify genetic risk factors in numerous diseases, such as systemic autoimmune diseases. The goal of GWAS is to identify these genetic risk factors in order to make predictions about who is at risk and investigate the biological process of disease susceptibility. There are several valuable mouse models to investigate the underlying mechanisms causing systemic autoimmune diseases in which mercury induced autoimmunity (HgIA) is a well-established and relevant model. HgIA in mice includes development of autoantibodies, immune complex glomerulonephritis, lymphocyte proliferation, hypergammaglobulinemia and polyclonal B cell activation. In humans, mercury exposure accumulates with considerable concentrations in kidney, liver, and brain. Toxicokinetics of Hg has been studied extensively but the key for inter-individual variation in humans are largely unclear. Differences in accumulation of renal Hg between inbred mouse strains suggest a genetic inter-strain variation regulating retention or/and excretion of Hg. OBJECTIVES: To find loci and candidate genes associated with phenotypes involved in the development of autoimmunity and find candidate genes involved in the regulation of renal Hg excretion. METHODS: MHC II (H-2 s) mice were paired (A.SW x B10.S) to achieve F2 offspring exposed to 2.0 or 4.0 mg Hg in drinking water for 6 weeks. Mercury induced autoimmune phenotypes were studied with immunofluorescence (anti-nucleolar antibodies (ANoA)), ELISA anti-DNP/anti-ssDNA (polyclonal B cell activation), anti-chromatin antibodies (ACA) (4.0 mg Hg), and serum IgG1 concentrations. Mercury accumulation in kidney was performed previously and data was included as phenotype. F2 mice exposed to 2.0 mg Hg were genotyped with microsatellites for genome-wide scan with Ion Pair Reverse Phase High Performance Petra Cassel, thank you for being there whenever I needed help. I know that there were many things that had nothing to do with you, but you still helped me and I appreciate that a lot. I sit in the corridor were no one else sits (except for when Said and students were there). So you and Camilla Janefjord were my daily colleagues I met every day and more or less the first that I said hi/good morning to. In some way, when I think of AIR, I actually think of you. You are the ones that represents it, how does that feel? . Sandra Hellberg, You are a very smart and kind person. We have always bumped in to each other in different occasions: being host in PhD party or being base group tutors together. You always take initiativ...

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The genetics and molecular pathogenesis of systemic lupus erythematosus (SLE) in populations of different ancestry

Cited by 116 publications

References 187 publications

Inhibitory B cell co-receptors and autoimmune diseases

Inhibitory B cell co-receptors and autoimmune diseases

Rheumatoid arthritis and systemic lupus erythematosus: Pathophysiological mechanisms related to innate immune system

Identification of candidate genes involved in Mercury Toxicokinetics and Mercury Induced Autoimmunity

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