Objective

Systemic lupus erythematosus (SLE) occurs predominantly in women, and hormones may play a role in its etiology. This study was carried out to examine associations between female reproductive and menopausal factors and the development of SLE.



Methods

A cohort of 238,308 women was prospectively examined. Subjects were older women (ages 30–55 years at start) and younger women (ages 25–42 years at start) from the Nurses' Health Study (NHS) and NHSII cohorts. Incident SLE diagnosed between 1976 and 2003 was confirmed by medical record review. The relative risk (RR) of SLE was estimated separately in each cohort using Cox proportional hazards models, and then pooled using meta-analysis random effects models.



Results

Two hundred sixty-two incident cases of SLE were confirmed among the women. In multivariable models adjusted for reproductive and other risk factors, age ≤10 years at menarche (pooled RR 2.1, 95% confidence interval [95% CI] 1.4–3.2), oral contraceptive use (pooled RR 1.5, 95% CI 1.1–2.1), and use of postmenopausal hormones (RR 1.9, 95% CI 1.2–3.1) significantly increased the risk of SLE. An elevation of SLE risk was observed among postmenopausal women primarily after surgical menopause (RR 2.3, 95% CI 1.2–4.5), and also among women with earlier age at natural menopause (P for trend < 0.05). Menstrual irregularity was associated with an increased risk of SLE among women in the younger (NHSII) cohort. Age at first birth, parity, and total duration of breastfeeding were not associated with SLE.



Conclusion

Early age at menarche, oral contraceptive use, early age at menopause, surgical menopause, and postmenopausal use of hormones were each associated with an increased risk of SLE. These associations may point to the mechanisms underlying the pathogenesis of SLE.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.22510

Reproductive and menopausal factors and risk of systemic lupus erythematosus in women.

Objective

Existing studies present conflicting evidence for the role of cigarette smoking as a risk factor in the development of systemic lupus erythematosus (SLE). We performed an extensive search of the medical literature for all studies examining this relationship, and performed a meta-analysis to arrive at a more precise estimate of effect.



Methods

We performed a computerized literature search for all studies (in all languages), using Medline and EMBASE (1966 to present) and the Cochrane Collaboration database, and completed hand searches of relevant bibliographies and abstracts of conference proceedings. Several investigators systematically extracted data from the relevant studies. Unpublished data were obtained from the author of one abstract. Studies were examined in aggregate for heterogeneity and publication bias. The relationships of current smoking and past smoking (prior to the onset of SLE) to development of SLE were analyzed separately.



Results

Fifty-two studies were identified and chosen for detailed review. Of these, 9 (7 case–control and 2 cohort studies) were appropriate for inclusion in our meta-analyses. For current smokers compared with nonsmokers, the odds ratio (OR) for development of SLE was significantly elevated (OR 1.50, 95% confidence interval [95% CI] 1.09–2.08). Former smokers, compared with nonsmokers, did not demonstrate an increased risk of SLE (OR 0.98, 95% CI 0.75–1.27). Several subgroups were also analyzed.



Conclusion

Our meta-analysis of the 7 existing case–control and 2 cohort studies revealed a small but statistically significant association between current smoking and development of SLE. However, no association between past smoking and development of SLE was observed.

Cigarette smoking and the risk of systemic lupus erythematosus: a meta-analysis.

Gender and autoimmunity

https://www.cell.com/trends/molecular-medicine/pdf/S1471-4914(03)00051-0.pdf

Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?

Estrogen as an immunomodulator.

Prolactin is a peptide hormone produced by the anterior pituitary gland that is critical in lactation. Prolactin can also be produced by lymphocytes, and both B and T cells express prolactin receptors. These findings have suggested that prolactin has immunomodulatory functions. Studies in spontaneously autoimmune hosts have demonstrated a role for prolactin in augmenting autoreactivity. We chose to analyze prolactin effects on anti-DNA B cells in nonspontaneously autoimmune female BALB/c mice transgenic for the heavy chain of an anti-DNA antibody. Treatment with prolactin for 4 weeks induced a lupus-like phenotype with an increased number of transgene-expressing B cells, elevated serum anti-DNA antibody titers, and glomerular immunoglobulin deposits. Prolactin caused a decrease in the population of transitional B cells and an increase in mature follicular and marginal zone B cells. The DNA-reactive B cells had a follicular cell phenotype. Anti-DNA hybridomas demonstrated that prolactin alters selection of the naive B cell repertoire. The expansion and activation of anti-DNA B cells in prolactin-treated R4A-γ2b BALB/c mice was dependent on the presence of CD4+ T cells. Finally, treatment with prolactin was unable to break tolerance in R4A-γ2b transgenic C57Bl/6 mice, suggesting that responsiveness of the immune system to prolactin is genetically determined.

/pdf/prolactin-modulates-the-naive-b-cell-repertoire-179wa9bncx.pdf

Xian Chen

Papers

Prolactin modulates the naive B cell repertoire