Rheumatoid arthritis: a female challenge.
ABSTRACT Rheumatoid arthritis (RA) is two- to three-fold more frequent in women than in men and a strong association with sex hormones has been demonstrated. There is strong evidence that autoimmunity is under genetic control, and genes in sexual chromosomes can play a role in supporting the female prevalence. On the other hand, it is widely accepted that sex hormones--estrogens in particular--may regulate the immune response by favoring the survival of forbidden autoreactive clones and ultimately the prevalence of autoimmunity in women. Accordingly, estrogens have been suggested to be associated with the development of RA. Pregnancy in RA women is a common situation and most pregnant patients experience a remission. This has been closely related to a switch from Th1 to Th2 immune responses and to a decreased production of proinflammatory cytokines, at least in part supported by the changes of the hormonal profile in pregnancy. Pregnancy planning is required in RA in order to avoid unwanted complications. In particular, the need to control the disease requires safe use of antirheumatic drugs both during the pregnancy itself and in the breastfeeding period. Hormonal treatment for contraception is contraindicated in the case of positivity for antiphospholipid antibodies owing to the increased thrombophilic risk. Similarly, replacement hormonal treatment in postmenopausal women with RA to control osteoporosis is no longer recommended as a result of its ability to increase the cardiovascular risk closely associated with RA itself.
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ABSTRACT: Considerable evidence supports the hypothesis that estrogen prevents bone loss by blocking the bone marrow cell production of pro-osteoclastogenic cytokines. However, controversy remains on the role of candidate factors, such as tumor necrosis factor (TNF) and interleukin-6 (IL-6). To investigate the contribution of these cytokines to the pathogenesis of ovariectomy (OVX)-induced bone loss, OVX mice were treated with either TNF binding protein (TNFbp), an inhibitor of TNF, the anti-(IL-6) antibody (Ab) 20F3, or estrogen for the first 2 weeks after surgery. OVX caused a rapid decrease in trabecular bone volume (TBV) and an increase in in vivo bone resorption, as assessed by bone histomorphometry. Treatment with TNFbp completely prevented bone loss and the increase in both osteoclast formation and bone resorption induced by OVX, but had no effects in sham-operated controls. In contrast, treatment with anti-IL-6 antibody failed to prevent bone loss, and the increase in bone resorption and osteoclastogenesis induced by OVX. These data demonstrate that in nongenetically manipulated mice, the estrogen-regulated cytokine that plays a central role in the mechanism by which estrogen deficiency causes bone loss is not IL-6, but rather TNF.Journal of Bone and Mineral Research 07/1997; 12(6):935-41. · 6.13 Impact Factor
- Women s Health 07/2007; 3(4):417-20.
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ABSTRACT: In the past few years, our extensive knowledge of the mammalian immune system and our increasing ability to understand the genetic causes of complex human disease have opened a window onto the pathways that lead to autoimmune disorders. In addition to the well-established role of genetic variation that affects the major histocompatibility complex, a number of rare and common variants that affect a range of immunological pathways are now known to have important influences on the phenotypic diversity that is seen among autoimmune diseases. Recent studies have also highlighted a previously unanticipated interplay between the innate and adaptive immune system, providing a new direction for research in this field.Nature Reviews Genetics 01/2007; 7(12):917-28. · 41.06 Impact Factor