An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene

Sazzini, Marco; Zuntini, Roberta; Farjadian, Shirin; Quinti, Isabella; Ricci, Giampaolo; Romeo, Giovanni; Ferrari, Simona; Calafell, Francesc; Luiselli, Donata

doi:10.1038/gene.2009.43

Cited by 12 publications

(12 citation statements)

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“…14,15 One study also showed that TACI might be involved in innate immune functions, rather than only in adaptive immunity. 25 The controversial role of TACI in IgG production has been collectively shown in previous studies. Animal studies showed that TACI À / À mice were present with defective IgG secretion.…”

Section: Discussionmentioning

confidence: 74%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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IgG has a crucial role in humoral immune response. Serum IgG level is mainly determined under genetic control. To explore the genetic influence on serum IgG levels, a two-stage genome-wide association study (GWAS) was performed in a healthy Chinese population of 3495 men, including 1999 unrelated subjects in the first stage and 1496 independent individuals in the second stage. Three single-nucleotide polymorphisms (SNPs) located in TNFRSF13B on 17p11.2 or nearby were significantly associated with IgG level: rs4792800 in the intron (combined P-value ¼ 1.45 Â 10 À 12 ), rs12603708 in the intron (combined P-value ¼ 1.82 Â 10 À 8 ) and rs3751987 at B65 kb downstream of the 5 0 -UTR region of TNFRSF13B (combined P-value ¼ 3.67 Â 10 À 9 ). Additionally, smoking was identified to be associated with IgG level in both stages (Po0.001), but there was no significant interaction between smoking and the identified SNPs (P40.05). The strong association between variants at TNFRSF13B and IgG level may be helpful to further explore the biological mechanism by which the serum IgG is affected by transmembrane activator, calcium modulator and cyclophilin ligand interactor encoded by TNFRSF13B.Genes and Immunity (2012) 13, 509-513; doi:10.1038/gene.2012.26; published online 7 June 2012Keywords: IgG; genome-wide association studies; TNFRSF13B; TACI; smoking INTRODUCTION IgG, constituting some 80% of total serum immunoglobulin, is the most abundant class of antibodies (Ab) in serum and extracellular fluid. It has an important role in the defense against various pathogens, toxins and even cancers. 1 As the only isotype that can pass through the human placenta, IgG is able to protect the fetus in utero. 2 Meanwhile, IgG gets involved in chronic inflammatory processes contributed to the destruction of healthy tissues in autoimmune diseases, such as arthritis and systemic lupus erythematosus. 3 Serum IgG level varies considerably from one person to another, 4 but little when testing the same person repeatedly. 5 This variation in the serum IgG concentration reflects the balance among the rates of synthesis and catabolism. 6 Multitudinous environmental factors including infections, smoking and chemical compounds can contribute to this variation. 7-9 Reports of pedigree studies or twin studies 10,11 have shown that genetic factors are more important than environmental exposures in determining serum immunoglobulin level in human. 12,13 The values of genetic heritability was h 2 ¼ 0.617 þ 0.020 for IgG. 6 Besides, several studies in a population of common variable immunodeficiency patients or IgA deficiency patients implied that there might be an association between some gene loci and serum IgG level. 14,15 However, to the best of our knowledge, no study has ever been conducted to identify the immune loci directly involved in the regulation of the IgG level.Genome-wide association study (GWAS) is a powerful and unbiased tool for the identification of common genetic variants associated with complex traits. 16 This hypothesis-free approach base...

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Section: Discussionmentioning

confidence: 74%

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Liao

Zhang

et al. 2012

Genes Immun

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“…In this study, we have adopted the latter approach to investigate the contribution of rare variants to the etiology of idiopathic PD. Our working hypothesis is that an excess of rare variants may indicate the involvement of a gene in a complex disease such as idiopathic PD and that such excess of rare variants can be measured, even in moderate sample sizes by using statistics coming from the field of molecular evolution (33). In particular, we used Tajima's D statistic (34) to test for deviations in the allele frequency spectrum between cases and controls in both individual genes and different gene groups.…”

Section: Introductionmentioning

confidence: 99%

Mendelian genes for Parkinson's disease contribute to the sporadic forms of the disease†

Spataro

Calafell

Cervera-Carles

et al. 2014

Human Molecular Genetics

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Parkinson's disease (PD) can be divided into familial (Mendelian) and sporadic forms. A number of causal genes have been discovered for the Mendelian form, which constitutes 10-20% of the total cases. Genome-wide association studies have successfully uncovered a number of susceptibility loci for sporadic cases but those only explain a small fraction (6-7%) of PD heritability. It has been observed that some genes that confer susceptibility to PD through common risk variants also contain rare causing mutations for the Mendelian forms of the disease. These results suggest a possible functional link between Mendelian and sporadic PD and led us to investigate the role that rare and low-frequency variants could have on the sporadic form. Through a targeting approach, we have resequenced at 49× coverage the exons and regulatory regions of 38 genes (including Mendelian and susceptibility PD genes) in 249 sporadic PD patients and 145 unrelated controls of European origin. Unlike susceptibility genes, Mendelian genes show a clear general enrichment of rare functional variants in PD cases, observed directly as well as with Tajima's D statistic and several collapsing methods. Our findings suggest that rare variation on PD Mendelian genes may have a role in the sporadic forms of the disease.

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“…We found that numerous cytokines including interleukins, interferons, chemokines, and TNFs were more abundant in DEW and SP compared with HI ( Figure 2; Table 1). The TNF receptor superfamily member 13B (TNFRSF13B) was mainly expressed on the surface of B-cell subpopulations such as CD27+ memory B-cells, and bound to the TNF ligands B-cell activating factor and a proliferationinducing ligand that functioned in the regulation of isotype switching, survival and B-lymphocyte differentiation in a complex functional network that was important for humoral responses (20,21). Coding variants of TNFRSF13B have been implicated in common variable immunodeficiency, and the variant TNFR13BV was found to be up-regulated in both DEW and SP, and the expression was two-fold higher in SP than in DEW ( Table 1).…”

Section: Cytokinesmentioning

confidence: 99%

Proteomic profiling change during the early development of silicosis disease

Miao¹,

Ding²,

Xin³

et al. 2016

J. Thorac. Dis.

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Background: Silicosis is one of several severe occupational diseases for which effective diagnostic tools during early development are currently unavailable. In this study we focused on proteomic profiling during the early stages of silicosis to investigate the pathophysiology and identify the proteins involved.Methods: Two-dimensional (2D) gel electrophoresis and MALDI-TOF-MS were used to assess the proteomic differences between healthy individuals (HI), dust-exposed workers without silicosis (DEW) and silicosis patients (SP). Proteins abundances that differed by a factor of two-fold or greater were subjected to more detailed analysis, and enzyme linked to immunosorbent assay (ELISA) was employed to correlate with protein expression data.Results: Compared with HI, 42 proteins were more abundant and 8 were less abundant in DEW, and these were also differentially accumulated in SP. Closer inspection revealed that serine protease granzyme A, alpha-1-B-glycoprotein (A1BG) and the T4 surface glycoprotein precursor (TSGP) were among the up-regulated proteins in DEW and SP. Significant changes in serine proteases, glycoproteins and protooncogenes may be associated with the response to cytotoxicity and infectious pathogens by activation of T cells, positive regulation of extracellular matrix structural constituents and immune response, and fibroblast proliferation. Up-regulation of cytokines included TNFs, interferon beta precursor, interleukin 6, atypical chemokine receptor 2, TNFR13BV, and mutant IL-17F may be involved in the increased and persistent immune response and fibrosis that occurred during silicosis development.Conclusions: Granzymes, glycoproteins, cytokines and immune factors were dramatically involved in the immune response, metabolism, signal regulation and fibrosis during the early development of silicosis.Proteomic profiling has expanded our understanding of the pathogenesis of silicosis, and identified a number of targets that may be potential biomarkers for early diagnosis of this debilitating disease. J Thorac Dis 2016;8(3):329-341 jtd.amegroups.com extracellular apoptosis related factor (ECM), cytokines and lipid-associated proteins were all reportedly involved in the development of silicosis (3,4). Unfortunately, an effective method involving biomarkers for early diagnosis remained unavailable at present.Significant cellular and molecular alterations ensued following inhalation and deposition of silica minerals in lung tissues (5). Lower-level exposure to silica particles triggered reversible inflammatory lesions, whereas highlevel exposure led to long-term effects on inflammation, cell proliferation, deposition of collagen and extracellular matrix components in mesenchymal cells (1). Alveolar macrophages (AM), neutrophils, T-lymphocytes and mast cells were all involved in fibrogenesis, and cross-talk between these cells played an important role in disease progression. In studies on the interaction of mast cells and neutrophils in mice, animals with intact mast cells endured more severe lung lesi...

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An evolutionary approach to the medical implications of the tumor necrosis factor receptor superfamily member 13B (TNFRSF13B) gene

Cited by 12 publications

References 59 publications

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Genome-wide association study identifies common variants at TNFRSF13B associated with IgG level in a healthy Chinese male population

Mendelian genes for Parkinson's disease contribute to the sporadic forms of the disease†

Proteomic profiling change during the early development of silicosis disease

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