Abstract

Women will hardly ever get their first signs of rheumatoid arthritis (RA) during pregnancy, whereas the onset of RA seems to cluster in the postpartum period. This clinical and epidemiological observation may be explained by a postponement of the onset of symptomatic RA by pregnancy, which is in line with the observed amelioration of disease activity in women with established RA. Up to 75% of women with RA improve during pregnancy, starting in the first or second trimester with maximum improvement during the third trimester of pregnancy. More than 90% of these patients will experience a flare of their disease within two to six months after delivery. Women who have ever been pregnant have a lower risk of developing RA, particularly when they had their first pregnancy at an early age. Several biological mechanisms have been put forward to explain the favourable effect of pregnancy on the onset and course of RA, but there is still no fully satisfactory explanation. The profound hormonal shifts (e.g. increased estrogens, progesterone and corticosteroids) have been implicated in the favourable effect of pregnancy through their effect on the immune system. Pregnancy is an immunological challenge requiring immunological protection or tolerance for the partly non-self fetus. Cellular immunity is decreased during pregnancy, which may play a role in the positive effect of pregnancy in RA. Pregnancy is associated with decreased production of TH1 associated cytokines (IL2, interferon gamma), increased production of TH2 associated cytokines (IL-4, IL-10), and decreased production of proinflammatory cytokines (TNF alpha, IL-12). Alterations in the glycosylation of IgG have also been put forward as a possible explanation. The question why not all women improve during pregnancy is still not answered by the above mechanisms. There is some evidence that HLA disparity between mother and fetus will play a role in the suppression of autoimmunity, which will differ between different pregnancies. A better understanding in how pregnancy exerts its effect on the onset and course of RA will help to unravel possible immunological mechanisms in RA and may lead to more effective treatments.

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