Estrogen alters thresholds for B cell apoptosis and activation

Grimaldi, Christine; Cleary, J.; Dagtas, A. Selma; Moussai, Dariush; Diamond, Betty

doi:10.1172/jci0214873

Cited by 404 publications

(242 citation statements)

References 54 publications

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“…40 Considerable evidence supports the hypothesis that depressed levels of CD22 on B cells can promote IgG ANA production. [41][42][43] In contrast to our results, Grimaldi et al 44 found that mRNA and surface protein expression of Cd22 were upregulated in response to E2 in BALB/c mice and proposed that this upregulation may be involved in the escape of autoreactive B cells from tolerance. Differences in the dose of E2 used or the genetic background of the mice may have contributed to this discordance.…”

Section: Discussioncontrasting

confidence: 99%

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

2007

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Ninety percent of systemic lupus erythematosus patients are female, and gender differences in lupus susceptibility are also observed in (New Zealand Black Â New Zealand White)F1 (BWF1) lupus-prone mice. We followed orchiectomized, intact male and female BWF1 mice for lupus-like disease for 1 year. A comparative gene expression analysis was then used to identify candidate genes potentially responsible for gender-dependent differences in lupus susceptibility. Seven genes encoded on the sex chromosomes and 77 probe sets, including 14 immunoglobulin genes, encoded on the autosomal chromosomes were identified as differentially expressed in male versus female BWF1 splenocytes prior to disease onset. Five genes were determined to be regulated by either estradiol or dihydrotestosterone in an in vivo system and most of them were preferentially expressed in antigen-presenting cells. Gender differences in the expression of Csf3-r, Histh1c, Serpinb2, Slc6a4 and Cd22 in BWF1 mice are the result of transcriptional modification by sex hormones and warrant further investigation. The identification of candidate genes and their expression patterns in splenocyte sub-populations provide new information regarding the mechanisms by which sex hormones influence the development of mouse lupus.

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Section: Discussioncontrasting

confidence: 99%

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

2007

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“…Overall, these data suggest that estrogens favor the development and/or exacerbation of the disease, while androgens seem to be protective (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17).…”

Section: Systemic Lupus Erythematosus (Sle) Is An Autoimmune Disease mentioning

confidence: 93%

Menopause hormonal therapy in women with systemic lupus erythematosus

Sánchez‐Guerrero

González-Pérez

Durand-Carbajal

et al. 2007

Arthritis & Rheumatism

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Objective. To evaluate the effects of menopause hormonal therapy on disease activity in women with systemic lupus erythematosus (SLE).Methods. We conducted a double-blind, randomized clinical trial involving 106 women with SLE who were in the menopausal transition or in early or late postmenopause. Patients received a continuoussequential estrogen-progestogen regimen (n ‫؍‬ 52) or placebo (n ‫؍‬ 54). Disease activity was assessed at baseline and at 1, 2, 3, 6, 9, 12, 15, 18, 21, and 24 months, according to the SLE Disease Activity Index (SLEDAI). The primary outcome measure was global disease activity, estimated by measuring the area under the SLEDAI curve. Secondary outcome measures included maximum SLEDAI score, change in SLEDAI score, incidence of lupus flares, median time to flare, medication use, and adverse events. Results were studied using intent-totreat analysis.Results. At baseline, demographic and disease characteristics were similar in both groups. Mean ؎ SD SLEDAI scores were 3.5 ؎ 3.3 and 3.1 ؎ 3.4 in the menopause hormonal therapy and placebo groups, respectively (P ‫؍‬ 0.57). Disease activity remained mild and stable in both groups throughout the trial. There were no significant differences between the groups in global or maximum disease activity, incidence or probability of flares, or medication use. Median time to flare was 3 months in both groups. Thromboses occurred in 3 patients who received menopause hormonal therapy and in 1 patient who received placebo. One patient in each group died during the trial due to sepsis.Conclusion. Menopause hormonal therapy did not alter disease activity during 2 years of treatment. However, an apparently increased risk of thrombosis seems to be a real threat in women with SLE who receive menopausal hormone therapy.

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“…Magnetic bead sorting for B220 þ cells is commonly used to purify B cells and does not directly result in their activation. [52][53][54] The major caveat to this second approach is that gene expression profiles obtained through this method would be representative of a mixed population of cells, not a single subset; however, by judiciously choosing the tissues to examine, we can highly enrich for specific cell populations.…”

Section: Resultsmentioning

confidence: 99%

Defining a transcriptional fingerprint of murine splenic B-cell development

et al. 2008

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B-cell development occurs in a stepwise fashion that can be followed by the expression of B cell-specific surface markers. In this study, we wished to identify proteins that could contribute to the changes in expression of such markers. By using RNA from freshly isolated B220 þ cells, we hoped to reduce the effect of artifacts that occur during the isolation and amplification steps necessary to use flow cytometry analysis-sorted subsets in microarray experiments. Analyses comparing expression patterns from B220 þ 2-week bone marrow (pro-B, pre-B, immature B cells), 2-week spleen (predominantly transitional cells) and 8-week spleen (mainly mature B cells) yielded hundreds of genes. We also examined the B cell-activating factor (BAFF)-dependent effects on immature splenic B cells by comparing expression patterns in the spleen between 2-week A/J vs 2-week A/WySnJ mice, which lack functional BAFF receptor signaling. Genes that showed the expression differences between spleen and bone marrow samples were then analyzed through quantitative PCR on B-cell subsets isolated using two different sorting protocols. A comparison of the results from our study with the results from other analyses showed not only some overlap of preferentially expressed genes but also an expansion of other genes potentially involved in B-cell development.

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Estrogen alters thresholds for B cell apoptosis and activation

Cited by 404 publications

References 54 publications

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

Identification of candidate genes that influence sex hormone-dependent disease phenotypes in mouse lupus

Menopause hormonal therapy in women with systemic lupus erythematosus

Defining a transcriptional fingerprint of murine splenic B-cell development

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