Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development

Alkaissi, Hammoudi; Havarinasab, Said; Nielsen, Jesper Bo; Söderkvist, Peter; Hultman, Per

doi:10.1371/journal.pone.0199979

Cited by 10 publications

(7 citation statements)

References 55 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In human T cells, both methyl mercuric chloride and inorganic Hg induce mitochondrial dysfunction and glutathione depletion (17), leading to generation of reactive oxygen species (ROS) and apoptotic caspases (18). Another study using A.SW mice showed significantly lower Bank 1 (B-cell scaffold protein with ankyrin repeats 1) gene expression and higher NF-kB, TLR-9, IL-6, and TNF-α after Hg exposure, supporting the roles of Bank1 (produced mainly in B cells) and NF-kB as the key regulators of antinucleolar antibodies in HgIA (19).…”

Section: Mercurymentioning

confidence: 92%

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

2020

View full text Add to dashboard Cite

Environmental agents have been gaining more attention in recent years for their role in the pathogenesis of autoimmune diseases (ADs). Increasing evidence has linked environmental exposures, including trichloroethene (TCE), silica, mercury, pristane, pesticides, and smoking to higher risk for ADs. However, potential mechanisms by which these environmental agents contribute to the disease pathogenesis remains largely unknown. Dysbiosis of the gut microbiome is another important environmental factor that has been linked to the onset of different ADs. Altered microbiota composition is associated with impaired intestinal barrier function and dysregulation of mucosal immune system, but it is unclear if gut dysbiosis is a causal factor or an outcome of ADs. In this review article, we first describe the recent epidemiological and mechanistic evidences linking environmental/occupational exposures with various ADs (especially SLE). Secondly, we discuss how changes in the gut microbiome composition (dysbiosis) could contribute to the disease pathogenesis, especially in response to exposure to environmental chemicals.

show abstract

Section: Mercurymentioning

confidence: 92%

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

2020

View full text Add to dashboard Cite

show abstract

“…[14] Recent studies have shown that Bank1 and NF-κB subunit 1 played critical regulatory role in antinucleolar antibodies in mercuryinduced autoimmunity in mice. [15] However, the association of IKBKE and BANK1 gene polymorphisms of SLE in the Han population of southwest China remained unclear. Based on this background, this study investigated the association of IKBKE rs15672 and BANK1 rs12640056 gene polymorphisms and susceptibilities of SLE in Han population of southwest China.…”

Section: Discussionmentioning

confidence: 99%

Genetic Association of rs15672 and rs12640056 Polymorphisms with the Susceptibility of Systemic Lupus Erythematosus in a Chinese Population

Zhang

Zhai

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

In this study, we aimed to investigate the relationship of IKBKE rs15672 and BANK1 rs12640056 gene polymorphisms with systemic lupus erythematosus (SLE) susceptibility in China. A case-control study was performed on 567 SLE patients and 345 healthy controls. Six single nucleotide polymorphisms (rs15672, rs2296164, rs12640056, rs6842661, rs1957106 and rs2274064) and clinical features were analyzed. Genotyping was executed with improved multiplex ligation detection reaction assay. SNP rs15672 increased the risk (P = 0.028, OR = 1.25, 95%CI = 1.02–1.52) but rs12640056 decreased the risk of SLE (P = 0.015, OR = 0.78, 95%CI = 0.64–0.95). For rs15672, patients carrying allele A assumed high-level IL-6 (25.36 ± 4.64 vs 16.56 ± 2.95, P = 0.036) and IL-4 (12.06 ± 4.51 vs 4.88 ± 1.76, P = 0.047), but low-level granzyme B (14.07 ± 1.86 vs 18.38 ± 3.85, P = 0.023), IL-18 (267.39 ± 14.67 vs 348.57 ± 44.25, P = 0.002) and IL-33 (0.91 ± 0.26 vs 2.19 ± 1.35, P = 0.029). Organ injury showed that mutant genotype at rs15672 had high-prevalence of arthritis (32.02%) and serositis (34.78%), but low in neuropathy (9.09%). For rs12640056, patients carrying allele T assumed low-level IL-33 (0.46 ± 0.17 vs 2.16 ± 1.00, P = 0.009). In conclusion, gene polymorphisms of rs15672 and rs12640056 present relevant with susceptibility of SLE, and affect the expression of cytokine and organ injury.

show abstract

“…During this period, researchers published various results that did not always correlate between papers [153]. This is because Hg triggers an autoimmune manifestation that is dose, time, gender and strain dependent [41,154]. This can be solved by calculating the internal Hg dose in mice, but the internal dose differs most of the time between studies.…”

Section: Discussionmentioning

confidence: 99%

“…These tandem repeats are found throughout the genome composed of di-, tri-, tetra-or bigger repeats (Fig 2). Genes are co-segregated with the highly polymorphic microsatellites, which make them useful markers for mapping studies [38][39][40][41]. SNPs occur naturally in the human population and is a variation of a single nucleotide replaced with different nucleotide.…”

Section: Genome Wide Association Studymentioning

confidence: 99%

“…caused by non-H-2 genes in HgIA. By performing GWAS using H-2 congenic mouse strains (H-2 s ) and their F1-and F2-hybrids, followed by fine mapping the QTL, there was a linkage between ANoA and the two genes, Bank1 and Nfb2, involved in the intracellular pathway of BCR activation [41]. Knockout studies in HgIA in mice have shown that IL-6 -/-, CD28 -/-, and…”

Section: Mercury Induced Autoimmunitymentioning

confidence: 99%

See 1 more Smart Citation

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

Alkaissi¹

2018

Linköping University Medical Dissertations

Self Cite

View full text Add to dashboard Cite

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...

show abstract

Bank1 and NF-kappaB as key regulators in anti-nucleolar antibody development

Cited by 10 publications

References 55 publications

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

Environmental Exposures and Autoimmune Diseases: Contribution of Gut Microbiome

Genetic Association of rs15672 and rs12640056 Polymorphisms with the Susceptibility of Systemic Lupus Erythematosus in a Chinese Population

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

Contact Info

Product

Resources

About