Review
Interaction of pregnancy and autoimmune rheumatic disease

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Abstract

During pregnancy, the fetus represents a natural allograft that is not normally rejected. While the maternal immune system retains the ability to respond to foreign antigens, tolerance mechanisms are up-regulated to protect the fetus from immunologic attacks by the mother. The profound immunologic adaptations during and after pregnancy do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease.

The review will discuss the mechanisms of increased susceptibility of rheumatoid arthritis (RA) in the first year post partum with a specific emphasis on the role of fetal cells or antigens persisting in the maternal circulation (so called microchimerism). Furthermore, the different influences of pregnancy on established rheumatic diseases will be highlighted. A marked beneficial effect of pregnancy is observed on RA whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no p]articular effect or an aggravation of symptoms during pregnancy. Differences emerging in regard to modulation of disease symptoms during pregnancy seem related to response to hormones, the type of cytokine profile and immune response prevailing as well as further downstream interactions of molecular pathways that are important in disease pathogenesis.

Introduction

Pregnancy induces dramatic immune and neuroendocrine alterations in the maternal body in order to protect the fetus from immunologic attack by the mother [1]. Instead of a general immunosuppression that would weaken the mother's defence against infection, rather a modulation of composition and function of immune-competent cells and immune-modulatory molecules takes place in the maternal system during pregnancy [2]. There is a cross-talk between mother and fetus from early on which helps to accommodate the fetus in the uterus, and supports nidation, placentation and fetal growth and development. On the other hand, the fetus promotes tolerance to paternal antigens by migration of fetal cells and cell-free fetal DNA into the maternal circulation during normal pregnancy. Fetal cells remain in the mother for decades, and create a state of microchimerism in the mother [3].

After delivery, the maternal body adjusts again to a non-pregnant state, which is not simply a return to the condition before conception, but takes place still under the influence of the immune activation at parturition [4]. Furthermore, lactation affects immune functions which may modulate activity of autoimmune diseases. The profound immunologic adaptions necessary for maternal tolerance toward the fetus in pregnancy and the immunologic reset to a non-pregnant state thereafter, do influence maternal autoimmune rheumatic diseases in several ways. One is triggering the onset of a rheumatic disease in the post partum period, the other influencing disease activity of established rheumatic disease.

Section snippets

Onset of arthritis

An increased incidence of autoimmune diseases has been observed in the post partum period [5]. In a Norwegian, population based study 37.7% out of 183 patients with rheumatoid arthritis (RA) and 28.2% out of 110 patients with other chronic arthritides (OCA) including psoriatic arthritis, ankylosing spondylitis (AS) and undifferentiated arthritis were diagnosed during the first 24 months after delivery (p = 0.09). The incidence rate ratio for diagnosis during 0–24 months versus 25–48 months post

The influence of pregnancy on established rheumatic disease

A marked beneficial effect of pregnancy is observed in rheumatoid arthritis (RA) whereas several other rheumatic diseases as ankylosing spondylitis (AS) and systemic lupus erythematosus (SLE) show either no particular effect or an aggravation of symptoms during pregnancy. This observation is an indication of different pathophysiology at work in rheumatic diseases which results in a different response to the complex changes of pregnancy. In this survey, modulation of disease activity, not

The immune response in pregnancy

The unique condition of pregnancy with a peaceful coexistence of genetically different individuals has initiated a lot of research aimed at understanding the mechanism of tolerance. In parallel, also the beneficial or adverse effects of pregnancy on autoimmune diseases have been investigated. In the following a brief overview of several aspects of this research is presented in the context of rheumatic disease.

Pregnancy induces substantial changes in hormone levels starting with hormones

The immune response during pregnancy in healthy and diseased rheumatic women: presentation of own studies

The different clinical response of RA, AS and SLE to pregnancy initiated research into gestational factors influencing disease symptoms which is presented in the following.

Different aspects of the modulation of disease activity during and after pregnancy was studied by us in pregnant women with RA and AS and compared to findings in healthy pregnant women. The clinical differences observed in own prospective studies between pregnant patients with RA and AS [102] initiated studies of the cytokine

Aspects of different responses of rheumatic disease to pregnancy

As discussed above, investigations into the immunology of pregnancy can, at least in part, explain the amelioration of RA during pregnancy. By contrast, the sustained activity of SLE and AS, and even the propensity to flare during pregnancy has been much less investigated (Fig. 3).

Conclusion

The different responses of rheumatic diseases to pregnancy shed light on pathogenetic mechanisms important for disease onset and the activity of established disease. The gender disparity with higher incidence of autoimmune disease among women than among men might to some extent depend on reproduction. Research into factors promoting disease onset has revealed the possibility that disease susceptibility genes can be acquired through fetal cells in a woman without disease specific HLA alleles or

Disclosure

The authors declare no competing interests.

  • 1.

    Jamieson DJ, Honein MA, Rasmussen SA, Williams JL, Swerdlow DL, et al. (2009) H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 374: 451–458.

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    Robb RJ, Kreijveld E, Kuns RD, Wilson YA, Olver SD, et al. Type I-IFNs control GVHD and GVL responses after transplantation. Blood 118: 3399–3409.

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