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Immunology of pregnancy—pregnancy as a remission inducing agent in rheumatoid arthritis

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Abstract

A variety of hormonal and immunological alterations are induced by pregnancy in order to protect the semi-allogeneic fetus from rejection. Systemic effects of altered immunoregulation induced by pregnancy influence the activity of rheumatoid arthritis (RA) and other autoimmune diseases. Pregnancy induces improvement or even remission of disease activity in 75% of RA patients. This phenomenon has still not been explained, however, several attractive hypotheses related to the immunology of pregnancy emerge. Pregnancy polarizes the immune response towards a TH2 response, which may counterbalance the augmented TH1 response observed in RA. The increase of circulating inhibitors of proinflammatory cytokines occurring in pregnancy could act as a potent anti-inflammatory agent in joint inflammation. In what way the induction of T cell tolerance to fetal antigens or maternal-fetal HLA disparity modulates disease activity of RA has not been studied. The concept of regulatory T cells has been discussed in the context of pregnancy, but until now has not been substantiated by experimental data. In conclusion, pregnancy influences the signs and symptoms of RA, but not the underlying autoimmune process. It remains to be investigated if a single event like neutralisation of proinflammatory cytokines or an interplay between circulating and cellular mechanisms is the key to remission.

Section snippets

Introductory remarks

Systemic effects of altered immunoregulation induced by pregnancy influence the activity of rheumatoid arthritis (RA) and other autoimmune diseases [1]. There are principally two ways to address the question of how pregnancy may modulate systemic autoimmune diseases. The classical way is to review and summarize the literature and to combine the conclusions of the different researchers. Alternatively, one can try to deduce a hypothesis from clinical observations and evolutionary rules. We will

Immunmodulation during pregnancy

The acceptance of the semiallogeneic fetus by the immunocompetent mother has puzzled immunologists for decades. Mechanisms responsible for accepting the fetus during pregnancy on one side and acceptance of an organ allograft in transplantation are shown in Fig. 1. In the following sections, mechanisms of acceptance in pregnancy are discussed.

Pathology of RA

RA is an autoimmune chronic inflammatory disorder of unknown etiology occurring in approximately 1% of the population worldwide. Women are three times more often affected than men. The disease is characterized by symmetrical polyarthritis and extraarticular manifestations including serositis, vasculitis and subcutaneous nodules. The latter indicate the presence of autoimmune features with the production of rheumatoid factor as a hallmark. Susceptibility of RA is associated with certain subtypes

Effects of pregnancy on RA

Pregnancy induces improvement or even remission of disease activity in 75% of RA patients [39]. More than 50% of pregnant RA patients experience improvement in the first trimester, and the maximum of improvement is for the majority reached at midgestation. Reactivation of the disease occurs for approximately 90% of patients within the first 6 months after delivery.

The findings of immunoregulatory mechanisms in pregnancy together with the results from studies on the pathogenesis of RA lead to

Conclusion

Pregnancy influences disease activity of RA, but it does not alter the evolution of the disease. Circulating and cellular mechanisms of pregnancy may be operative in the induction of remission. It is conceivable that several regulatory pathways act in concert, however, as the successful intervention with TNF inhibition in RA indicates, also a single regulatory mechanism might be responsible for disease remission.

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