Israel Medical Association Journal

Systemic sclerosis (SSc) is characterized by extensive collagen deposition, microvasculopathy and autoantibodies. All three features can be promoted by activation of T cells and B cells. T cells are of Th2 type producing profibrotic cytokines IL-4 and IL-13 and inducing dendritic cell maturation that promotes Th2 response. B cells are overactivated and promote fibrosis by autoantibodies that activate fibroblasts or inhibit the degradation of extracellular matrix. They also promote fibrosis by cell-cell contact with fibroblasts or dendritic cells. B cells, through autoantibodies, may promote vasoconstriction and obliterative vasculopathy. They may also sustain activation of T cells by functioning as antigen-presenting cells. An immunoregulatory subset of B cells, namely IL-10-producing Bregs, is decreased in SSc. Finally, B cells have a critical role in animal models of SSc. All this evidence suggests an important role for B cells in the pathogenesis of SSc and makes B cells a potential target for therapeutic intervention in this disease. 

 

Antiphospholipid syndrome (APS) is an autoimmune systemic disease characterized by vascular thrombosis (arterial or venous) and/or pregnancy complications associated with the occurrence of autoantibodies, specifically lupus anticoagulant, anticardiolipin antibodies, and/or anti-β2 glycoprotein-I antibodies confirmed at least twice over a 12 week period according to the 2006 Sydney criteria. Antiphospholipid antibodies are encountered  in the general population with a reported prevalence of 1% to 5%  However, APS is far more infrequent with a prevalence of 40–50/100,000 persons and an incidence of about 5 new patients/100,000 persons. APS can be diagnosed in patients with no apparent clinical or laboratory pathology (primary APS) or it may be related to numerous other conditions, autoimmune diseases (usually systemic lupus erythematosus), malignancies, infections and drugs (secondary APS). Women are at risk for APS since the disease is encountered in both the primary and the secondary state in females more often than in men. In addition, women in their reproductive years can develop APS (either classical or obstetric), and special attention is warranted in pregnant women with a diagnosis of APS. The benefits of hormonal therapy in the form of contraception or hormone replacement treatment should be carefully weighed against the increased risk for vascular complications in women with APS.

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin.

Objectives: To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels.

Methods: In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. 

Results: Patients’ age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0–20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. 

Conclusions: In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

 

Women who carry the BRCA gene mutation have an up to 80% chance of developing cancer, primarily of breast and ovarian origin. Confirmation of carrier status is described by many women as an overwhelming, life-changing event. Healthy individuals harboring a BRCA mutation constitute a high risk population with unique needs, often overlooked by health authorities. As such, we felt the need to create a specialized service dedicated specifically to this high risk population. The clinic staff comprises an experienced multidisciplinary team of health professionals who can support the medical and emotional needs of this population. Since its inception in 2001 the clinic has served 318 women. The mean age of patients is 46 years. With a median follow-up of 46 months, 21 women have developed malignancies, including 17 breast cancers, 1 ovarian cancer and 3 additional cancers. All but one of the patients above the age of 40 underwent bilateral salpingo-oophorectomy (BSO). The median and mean ages at BSO were 46.5 and 48 years, respectively (range 33–68). However, only 28.3% underwent bilateral preventive mastectomy. A multidisciplinary clinic for BRCA mutation carriers provides a “home” for this unique population with unmet needs. The high rate of BSO in women before natural menopause indicates that both the medical community and this population are aware of international guidelines supporting this procedure. We believe that a dedicated clinic, with a multidisciplinary team, is likely to contribute to the health, quality of life and survival of BRCA carriers.

Background: Both cigarette smoking and chronic kidney disease (CKD) are linked to cardiovascular morbidity and development of atherosclerosis. However, the relationship between cigarette smoking and renal function is not clearly understood. 

Objectives: To investigate the relationship between cigarette smoking and renal function, and determine whether the intensity of cigarette smoking influences renal function.

Methods: We conducted a retrospective analysis of subjects attending the screening center at the Rabin Medical Center. Subjects were classified as smokers, non-smokers and past smokers. Renal function was evaluated by means of the CKD-EPI equation for estimating glomerular filtration rate (eGFR). Multivariate and gender-based analyses were performed.

Results: The study population comprised 24,081 participants, of whom 3958 (17%) were classified current smokers, and 20,123 non-smokers of whom 4523 were classified as past smokers. Current smokers presented a higher eGFR compared to the non-smoking group (100.8 vs. 98.7, P < 0.001) as well as higher rates of proteinuria (15.3% vs. 9.3%, P < 0.001). The difference in eGFR between smokers and non-smokers was more significant in males than in females. Past smokers had the lowest eGFR of all groups, this difference remained significant after age adjustments (P = 0.005). 

Conclusions: Cigarette smoking is associated with higher eGFR compared to non-smoking. This difference was more pronounced in males than females, implying a gender-based difference. The higher prevalence of proteinuria in smokers suggests a mechanism of hyperfiltration, which might result in future progressive renal damage.