Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus

Salazar-Camarena, Diana Celeste; Ortiz‐Lazareno, Pablo César; Cruz, Álvaro; Edith, Oregon-Romero; Machado-Contreras, Jesús René; Muñoz‐Valle, José Francisco; Orozco-López, Mariana; Marín‐Rosales, Miguel; Palafox‐Sánchez, Claudia Azucena

doi:10.1177/0961203315608254

Cited by 115 publications

(89 citation statements)

References 47 publications

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“…The pathways through which GC B cell tolerance break down are not clear, but in mouse models it was recently shown that IFN-γR signaling in B cells as well as B cell IFN-γ production were critical initial steps for spontaneous GC development leading to autoimmunity6162. Interestingly, SLE patients also display increased BAFF serum levels that correlate with disease activity63. In accordance with this, BAFF blockade (belimumab) is the first U.S. Food and Drug Administration-approved treatment of SLE using a biologic.…”

Section: Discussionmentioning

confidence: 99%

IFN type I and II induce BAFF secretion from human decidual stromal cells

Lundell

Nordström

Andersson

et al. 2017

Sci Rep

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B cell activating factor (BAFF) is a critical cytokine for maturation of immature B cells. In murine lymph nodes, BAFF is mainly produced by podoplanin-expressing stromal cells. We have previously shown that circulating BAFF levels are maximal at birth, and that farmers’ children exhibit higher BAFF levels in cord blood than non-farmers’ children. Here, we sought to investigate whether maternal-derived decidual stromal cells from placenta secrete BAFF and examine what factors could stimulate this production. We found that podoplanin is expressed in decidua basalis and in the underlying villous tissue as well as on isolated maternal-derived decidual stromal cells. Decidual stromal cells produced BAFF when stimulated with IFN-γ and IFN-α, and NK cells and NK-T-like cells competent of IFN-γ production were isolated from the decidua. Finally, B cells at different maturational stages are present in decidua and all expressed BAFF-R, while stromal cells did not. These findings suggest that decidual stromal cells are a cellular source of BAFF for B cells present in decidua during pregnancy.

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Section: Discussionmentioning

confidence: 99%

IFN type I and II induce BAFF secretion from human decidual stromal cells

Lundell

Nordström

Andersson

et al. 2017

Sci Rep

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“…Elevated serum levels of the cytokines B lymphocyte stimulator (BLyS) and APRIL in SLE patients correlate with both disease activity (11,12) and autoantibody production (13)(14)(15)(16). These factors are therefore promising targets for new investigational therapies.…”

mentioning

confidence: 99%

8 Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a 24-week randomisedrandomized, placebo-controlled, phase iib study

Merrill

Wallace

Wax

et al. 2017

Plenary Session 3: Challenges in Drug Development and Clinical Trial Design in SLE

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“…We chose the following six genes for their potential role in the innate response: TNFSF13, PIK3R1, NFATC1, FES, TCF7 and RORA . The TNF superfamily 13, or APRIL, protein is a surface or secreted ligand recognized by the transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) and B-cell maturation antigen (BCMA) receptors and has been implicated in the pathogenesis of numerous pro-inflammatory conditions such as rheumatoid arthritis [56], atherosclerosis [57], lupus [58] and psioriasis [59]. Moreover, APRIL has been shown to activate NF-κB dependent cytokine production in macrophages [60] and keratinocytes [59].…”

Section: Discussionmentioning

confidence: 99%

Genome-wide methylation analysis reveals differentially methylated loci that are associated with an age-dependent increase in bovine fibroblast response to LPS

Korkmaz

Kerr

2017

BMC Genomics

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BackgroundDifferences in DNA methylation are known to contribute to the development of immune-related disorders in humans but relatively little is known about how methylation regulates immune function in cattle. Utilizing whole-transcriptome analyses of bovine dermal fibroblasts, we have previously identified an age and breed-dependent up-regulation of genes within the toll-like receptor 4 (TLR4) pathway that correlates with enhanced fibroblast production of IL-8 in response to lipopolysaccharide (LPS). Age-dependent differences in IL-8 production are abolished by treatment with 5-aza-2-deoxycytidine and Trichostatin A (AZA-TSA), suggesting epigenetic regulation of the innate response to LPS. In the current study, we performed reduced representation bisulfite sequencing (RRBS) on fibroblast cultures isolated from the same animals at 5- and 16-months of age to identify genes that exhibit variable methylation with age. To validate the role of methylation in gene expression, six innate response genes that were hyper-methylated in young animals were assessed by RT-qPCR in fibroblasts from animals at different ages and from different breeds.ResultsWe identified 14,094 differentially methylated CpGs (DMCs) that differed between fibroblast cultures at 5- versus 16-months of age. Of the 5065 DMCs that fell within gene regions, 1117 were located within promoters, 1057 were within gene exons and 2891 were within gene introns and 67% were more methylated in young cultures. Transcription factor enrichment of the promoter regions hyper-methylated in young cultures revealed significant regulation by the key pro-inflammatory regulator, NF-κB. Additionally, five out of six chosen genes (PIK3R1, FES, NFATC1, TNFSF13 and RORA) that were more methylated in young cultures showed a significant reduction in expression post-LPS treatment in comparison with older cultures. Two of these genes, FES and NFATC1, were similarly down-regulated in Angus cultures that also exhibit a low LPS response phenotype.ConclusionsOur study has identified immune-related loci regulated by DNA methylation in cattle that may contribute to differential cellular response to LPS, two of which exhibit an identical expression profile in both low-responding age and breed phenotypes. Methylation biomarkers of differential immunity may prove useful in developing selection strategies for replacement cows that are less susceptible to severe infections, such as coliform mastitis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3796-1) contains supplementary material, which is available to authorized users.

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Association of BAFF, APRIL serum levels, BAFF-R, TACI and BCMA expression on peripheral B-cell subsets with clinical manifestations in systemic lupus erythematosus

Abstract: Decreased BCMA expression on peripheral B cells according to severe disease activity suggests that BCMA plays an important regulating role in B-cell hyperactivity and immune tolerance homeostasis in SLE patients.

Cited by 115 publications

References 47 publications

IFN type I and II induce BAFF secretion from human decidual stromal cells

IFN type I and II induce BAFF secretion from human decidual stromal cells

8 Efficacy and safety of atacicept in patients with systemic lupus erythematosus: results of a 24-week randomisedrandomized, placebo-controlled, phase iib study

Genome-wide methylation analysis reveals differentially methylated loci that are associated with an age-dependent increase in bovine fibroblast response to LPS

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