Beneficial effect of pregnancy on an autoimmune disease
What is Rheumatoid Arthritis?Rheumatoid arthritis (RA) is a chronic inflammatory disease of the joints that affects 1 in every 100 adults, and is among the leading causes of disability worldwide. RA results in inflamed and painful joints. It can also affect other organs. Why and how the disease occurs is still unknown; research in this field, however, has shown that genes as well as environmental exposures may contribute to the disease. Although there are medications to effectively manage the symptoms, these medications can have serious side effects and a significant proportion of patients do not respond to them. There is currently no cure for RA.
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The influence of pregnancy on RAIn 1938, Dr. Philip Hench first reported that RA symptoms in some of his patients had naturally improved during pregnancy. Since then, there have been numerous reports documenting the beneficial effects of pregnancy on RA. In approximately 48%-75% of women with RA who go through pregnancy, there is a natural and dramatic improvement of symptoms during pregnancy, a phenomenon that is yet to be explained; this is followed by a flare of disease activity by 3-4 months following childbirth. Many patients describe this natural improvement of RA during pregnancy as “better than any known treatment for the disease”.
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How does pregnancy exert this influence on RA?Decades ago, Dr. Hench had proposed that the natural improvement in symptoms and joint swelling of RA was due to an unidentified “anti-rheumatic Substance X” being produced during pregnancy. His research later led to the discovery of corticosteroids as a treatment for RA, a discovery for which he shared the Nobel Prize in Physiology or Medicine in 1950. However, the identity of the mysterious anti-rheumatic substance X remains unsolved. Hormonal changes during pregnancy seem to be an obvious benefactor; however, hormonal changes do not explain why arthritis improves in most, but not all, patients. Nor do increased levels of cortisol as Dr. Hench had thought.
A pregnancy-specific factor that may be involved in the pregnancy-induced amelioration of RA is exposure of the mother to paternal versions of specific genes (called HLA genes) inherited by the fetus - that differ from the versions that the mother has (maternal-fetal HLA disparity). Small numbers of cells from the fetus have also been found to persist in the mother years after the pregnancy, a phenomenon known as microchimerism. Interestingly, microchimerism of fetal origin may impact risk that a healthy woman might develop RA, either increasing or decreasing risk depending on the specific paternal version of the HLA gene.
Still, this field of research has been incompletely explored, due in part to difficulties in identifying women with RA for pregnancy research. As a result, we do not currently understand how pregnancy brings about a natural improvement of RA, what leads to a flare after childbirth, and why some patients do not experience improvement during pregnancy.
We have performed a pilot study to examine how pregnancy-induced biological changes differ between women with RA who improve during pregnancy and those who worsen.To view our published paper, click on the reference below:
Goin D, Smed MK, Pachter L, Purdom E, Nelson JL, Kjærgaard H, Olsen J, Hetland ML, Zoffmann V, Ottesen B, Jawaheer D. Pregnancy-induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study. Arthritis Research & Therapy 2017 May 25;19(1):104. doi: 10.1186/s13075-017-1312-2.