Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

Kawasaki, Aya; Tsuchiya, Naoyuki; Fukazawa, Toru; Hashimoto, Hiroshi; Tokunaga, Katsushi

doi:10.1038/sj.gene.6363923

Cited by 102 publications

(81 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Weak associations with certain SNPs did not remain significant after correction for multiple testing, although associations with selected ethnicities and/or subgroups of SLE patients were identified (24). Those findings bring to mind the lack of genetic associations observed for SLE and gene polymorphisms of BLyS (25,26), a proinflammatory cytokine that, like leptin, is elevated in SLE, promotes SLE in mice and in humans (27), and is targeted for therapy in certain SLE patients (28).…”

Section: Discussionmentioning

confidence: 96%

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Leptin is an adipocytokine that plays a key role in the modulation of immune responses and the development and maintenance of inflammation. Circulating levels of leptin are elevated in systemic lupus erythematosus (SLE) patients, but it is not clear whether this association can reflect a direct influence of leptin on the propathogenic events that lead to SLE. To investigate this possibility, we compared the extent of susceptibility to SLE and lupus manifestations between leptin-deficient (ob/ob) and H2-matched leptinsufficient (wild-type, WT) mice that had been treated with the lupus-inducing agent pristane. Leptin deficiency protected ob/ob mice from the development of autoantibodies and renal disease and increased the frequency of immunoregulatory T cells (Tregs) compared with leptin-sufficient WT mice. The role of leptin in the development of SLE was confirmed in the New Zealand Black (NZB) × New Zealand White (NZW)F 1 (NZB/W) mouse model of spontaneous SLE, where elevated leptin levels correlated with disease manifestations and the administration of leptin accelerated development of autoantibodies and renal disease. Conversely, leptin antagonism delayed disease progression and increased survival of severely nephritic NZB/W mice. At the cellular level, leptin promoted effector T-cell responses and facilitated the presentation of self-antigens to T cells, whereas it inhibited the activity of regulatory CD4 T cells. The understanding of the role of leptin in modulating autoimmune responses in SLE can open possibilities of leptin-targeted therapeutic intervention in the disease.systemic lupus erythematosus | leptin | autoimmunity | immune regulation | animal models

show abstract

Section: Discussionmentioning

confidence: 96%

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Lourenço

Liu

Matarese

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Consistent with the results of their study, our findings revealed that primary immunodeficiency patients, including those with CVID, IgAD and XLA, showed increased plasma levels of BAFF and APRIL. It was suggested that primary antibody deficiency might have common immunological features such as monocyte activation (24)(25)(26)(27). It has been reported that inflammation and cytokines such as IFNγ or G-CSF in particular enhance BAFF production (28,29).…”

Section: Discussionmentioning

confidence: 99%

Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency

Jin

Kaneko²,

Suzuki³

et al. 2008

Int J Mol Med

View full text Add to dashboard Cite

Abstract. In some patients with common variable immunodeficiency (CVID) and immunoglobulin (Ig) A deficiency (IgAD), tumor necrosis factor (TNF) family receptor transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) gene mutations have been reported. B cells from individuals with TACI mutations do not produce IgG and IgA in response to the TACI ligand a proliferation-inducing ligand (APRIL) which probably suggests impaired isotype switching. To clarify the pathogenesis of CVID and IgAD of Japanese patients, we investigated the mutations of TNF family members TACI, APRIL, B-cell activating factor (BAFF), B-cell maturation antigen (BCMA) and BAFF receptor (BAFF-R) genes and the expression levels of BAFF and APRIL in patients with CVID, IgAD and X-linked agammaglobulinaemia (XLA). We also investigated the relationship between age and the blood plasma levels of BAFF and APRIL. The causative gene mutations of TNF family members in our patients were not detected. In healthy subjects, the BAFF and APRIL plasma levels correlated inversely with age. The BAFF and APRIL plasma levels of patients with CVID, IgAD and XLA were significantly higher than those of healthy children. Elevated BAFF and APRIL expression levels might partially reflect the common immunological feature of primary antibody deficiency.

show abstract

“…49 Thus, it is possible that this SNP may change the binding affinity of MZF1. 47 Further functional studies are necessary to clarify this possibility. Encouraging these studies is the fact that increased BLYS level was also observed in the serum or synovial fluid of human SLE, rheumatoid arthritis (RA) and Sjögren's syndrome.…”

Section: Expression Of Cd40l On T Cells Is Transient With the Ligandmentioning

confidence: 99%

“…A tendency for increase of the BLYS À871 T/T genotype was observed in a subgroup of SLE patients with anti-Sm antibodies and the BLYS mRNA level was significantly elevated in the monocytes from individuals having the À871T allele. 47 Elevated BLYS levels correlated with the presence of À871T was observed in patients with familial B-cell chronic lymphocytic leukemia as well. 48 The position À871 is located in the binding site of transcription factor MZF1, which was reported to be preferentially expressed in differentiating myeloid cells.…”

Section: Expression Of Cd40l On T Cells Is Transient With the Ligandmentioning

confidence: 99%

“…The A allele (105Thr) was absent in control individuals and had very low frequencies in Japanese RA (0.9%) and SLE (0.3%) patients. 47 Because allele frequencies may differ among populations we decided to analyze this polymorphism in the Brazilian population. The frequency observed in our control sample (0.4%) was similar that to that found in the Japanese population.…”

Section: Expression Of Cd40l On T Cells Is Transient With the Ligandmentioning

confidence: 99%

See 1 more Smart Citation

Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus

Malheiros

Petzl-Erler

2009

Genes Immun

View full text Add to dashboard Cite

Following the candidate gene approach we analyzed the CD40L, CD40, BLYS and CD19 genes that participate of B-cell co-stimulation, for association with pemphigus foliaceus (PF), an organ-specific autoimmune disease, characterized by the detachment of epidermal cells from each other (acantholysis) and presence of autoantibodies specific for desmoglein 1 (dsg1), an epidermal cell-adhesion molecule. The disease is endemic in certain regions of Brazil and also is known as fogo selvagem. Complex interactions among environmental and genetic susceptibility factors contribute to the manifestation of this multifactorial disease. The sample included 179 patients and 317 controls. Strong significant association was found with CD40LÀ726T4C (odds ratio, OR ¼ 5.54 and 0.30 for T þ and C þ genotypes, respectively). In addition, there were significant negative associations with CD40 À1T (OR ¼ 0.61) and BLYSÀ871T (OR ¼ 0.62) due to the decrease of the frequency of both homo-and heterozygotes in the patient group. No associations were found with variants of CD19 gene. Gene-gene interactions were observed between CD40 and BLYS, and between CD40L and BLYS. So, the dominant protective effects of CD40LÀ726C and of CD40 À1T only manifest in BLYSÀ871T þ individuals, and vice versa. We conclude that genetic variability of CD40L, CD40 and BLYS is an important factor for PF pathogenesis.

show abstract

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

Cited by 102 publications

References 33 publications

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Leptin promotes systemic lupus erythematosus by increasing autoantibody production and inhibiting immune regulation

Age-related changes in BAFF and APRIL profiles and upregulation of BAFF and APRIL expression in patients with primary antibody deficiency

Individual and epistatic effects of genetic polymorphisms of B-cell co-stimulatory molecules on susceptibility to pemphigus foliaceus

Contact Info

Product

Resources

About