Synergistic effect between IL10 and bcl2 genotypes in determining susceptibility to systemic lupus erythematosus

Mehrian, Ruty; Quismorio, Francisco P.; Strassmann, Gideon; Stimmler, Mary M.; Horwitz, David A.; Kitridou, Rodanthi C.; Gauderman, W. James; Morrison, John C.; Brautbar, Chaim; Jacob, Chaim O.

doi:10.1002/1529-0131(199804)41:4<596::aid-art6>3.3.co;2-u

Cited by 10 publications

(3 citation statements)

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“…To determine whether E 2 increases survival of anti-DNA B cells and up-regulates production of anti-DNA antibodies, female R4A-␥2b transgenic BALB͞c mice were implanted with P or E 2 pellets designed to release between 75 and 100 pg͞ml of 17␤-estradiol into the circulation for up to 60 days. Sera assayed by RIA displayed average E 2 concentrations of 16 pg͞ml (range, in both E 2 -and P-treated mice at week 0 and 94 pg͞ml (range, 50-130) in E 2 -treated mice and 24 pg͞ml (range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] in P-treated mice by 5 weeks of treatment.…”

Section: Resultsmentioning

confidence: 99%

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Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells

Bynoe

Grimaldi

Diamond

2000

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

245

198

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Sex hormones are presumed to contribute to sexual dimorphism in the immune system. Estrogen, in particular, has been suggested to predispose women to systemic lupus erythematosus. We report here that estradiol (E2) can break B cell tolerance and induce a lupus-like phenotype in nonautoimmune mice transgenic for the heavy chain of a pathogenic anti-DNA antibody. E2 treatment resulted in a rise in anti-DNA serum titers and in Ig deposition in renal glomeruli. ELISPOT analysis confirmed a significant increase in the number of high-affinity anti-DNA antibody-secreting B cells in the spleens of E2-treated mice. Hybridomas generated from E2-treated mice express high-affinity, unmutated anti-DNA antibodies, indicating that naïve B cells that are normally deleted or anergized are rescued from tolerance induction. Finally, immunohistochemical studies revealed increased Bcl-2 expression in splenic B cells of E2-treated mice. These data demonstrate that estrogen interferes with tolerance induction of naïve autoreactive B cells and that the presence of these B cells in the periphery is associated with up-regulation of Bcl-2.

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Section: Resultsmentioning

confidence: 99%

“…Studies performed with intragenic markers revealed that particular polymorphisms in the bcl-2 locus appear to be associated with susceptibility for SLE (35). It has also been reported that bcl-2 transcripts are increased in bone marrow cells from patients with SLE (36).…”

Section: Discussionmentioning

confidence: 99%

Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells

Bynoe

Grimaldi

Diamond

2000

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

245

198

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“…In non‐MHC genes, the Fas ligand 15 and the CD3 δ gene mutation 16 have been found to be associated with a subset of SLE. With respect to cytokine genes, specific genotypes of both IL‐10 and bcl‐2 have been associated with an increased risk of development of SLE 17 . Moreover, the greatest risk of development of SLE has been detected in individuals with the specific genotype combination IFN‐γR1 and IFN‐γR2 10 .…”

Section: Discussionmentioning

confidence: 99%

Correlation between some Th1 and Th2 cytokine receptor gene polymorphisms and systemic lupus erythematosus in Chinese patients

Yao

Chen

et al. 2007

Int J Dermatology

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Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus

et al. 1999

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Multiple genetic as well as environmental factors are considered to be involved in the development of systemic lupus erythematosus (SLE). A number of previous studies have suggested a possible role for tumor necrosis factor (TNF) in the pathogenesis of SLE. In addition, one of the candidate loci suggested by the genome-wide linkage analysis corresponds to the chromosomal position encompassing the TNF receptor 2 gene (TNFR2). The purpose of this study was to analyze the polymorphism of TNFR2 and its possible association with the susceptibility to SLE, using the case-control association analysis. Polymorphism screening of the exons containing previously reported nonsynonymous base substitutions was carried out by the polymerase chain reaction (PCR)-single strand conformation polymorphism (SSCP) method, using genomic DNA from 81 Japanese patients with SLE and 207 healthy individuals. Two alleles were present in exon 6, coding for methionine (196M) and arginine (196R) at position 196. 30 of 81 patients (37.0%) with SLE were positive for the 196R allele, which was significantly more frequent compared with 39 of 207 healthy individuals (18.8%) (chi2=10.6, df=l, P=0.001, odds ratio=2.53, 95% CI: 1.45-4.43). Genotype analysis revealed that the presence of one 196R allele was sufficient for rendering susceptibility. The association of 196R allele with SLE was independent from that of HLA-DRB1*1501. In conclusion, the TNFR2 196R allele was found to be significantly associated with the susceptibility to SLE in the Japanese population. Further population and functional studies will be of particular importance to establish TNFR2 as one of the susceptibility genes to SLE.

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Synergistic effect between IL10 and bcl2 genotypes in determining susceptibility to systemic lupus erythematosus

Cited by 10 publications

References 0 publications

Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells

Estrogen up-regulates Bcl-2 and blocks tolerance induction of naïve B cells

Correlation between some Th1 and Th2 cytokine receptor gene polymorphisms and systemic lupus erythematosus in Chinese patients

Association of tumor necrosis factor receptor 2 (TNFR2) polymorphism with susceptibility to systemic lupus erythematosus

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