AIDS, multiple sclerosis, type 1 diabetes, Rheumatoid Arthritis (RA). You might be wondering where this seemingly depressing list is heading, and that’s a fairly reasonable question. Each of these diseases is an autoimmune disease, meaning that the ones immune system is attacking its own body as if it were foreign. You might be familiar with some more than others, perhaps through the media, or through family and friends. What you might not know, is what kind of therapeutic agents are being employed in combating these diseases. One disease in particular, Rheumatoid Arthritis, affects ones joints, and causes a very painful inflammation as your body attacks its own joint tissues.1 While this doesn’t typically onset until later in one’s life, women in childbearing age can be affected. One phenomenon which has been observed is an actual regression of RA symptoms and potentially remission2. Unfortunately, the symptoms are reported to return post pregnancy.3 This then leads to the question what is happening during pregnancy that alleviates the symptoms and in some cases causes remission.
Many studies have been conducted to answer such a question, and the results are highly variable. Some studies point out that a certain type of immune cells, Th1, and its reduction during pregnancy may be responsible for the alleviation and remission of rheumatoid arthritis and symptoms.4 One particular study seeks to investigate the effects of regulatory T cells (Tregs) and how they might be interrupting the deleterious effects exhibited in RA. Whatever it may be that these studies are attempting to credit with the beneficial effects of pregnancy, they all work towards understanding the disease in order to understand how to better prevent it. If the immune system of pregnant women is able to “fight” off RA, perhaps understanding the mechanism will allow insight into how this can be converted into a publicly available treatment.
The aforementioned study, in which Tregs are hypothesized to be the cells responsible for the remission of RA symptoms, seeks to replicate the beneficial effects of pregnancy in order to further shed light on the mechanism. Experimenters infected mice with Collagen-Induced Arthritis (CIA), the “mouse model” of RA, post pregnancy, and their Tregs were then collected once they were considered pregnant-protected. The pregnant mice infected with CIA were compared to a set of non-pregnant mice also infected with CIA. Researchers found that there was only an 11% incidence of CIA in pregnant mice, compared to that of 35% in non-pregnant mice. Researchers also illustrated that pregnant mice were initiating a normal immune response; therefore the re-missive effects of pregnancy on RA could not be attributed to immune suppression.
In addition to proving that the beneficial effects of pregnancy were not solely immune suppression induced, researches sought to support their hypothesis of Tregs as the worker cells. The researchers took mice with CIA and gave them CD25+ cells (indicative of Tregs) from either non-pregnant mice, pregnant mice, or pregnant mice that had been infected with and since protected from CIA (pregnant-protected). Researchers then found that none of the mice who received CD25+ from pregnant protected mice developed arthritis while 24% of mice who received from non-pregnant and 32% who received from pregnant untreated developed arthritis. This shows that pregnancy alone does not protect against the effects of arthritis, instead the pregnant mice must have a prior exposure to arthritis in order to develop the appropriate antigens.
While this study is indeed conclusive of the tested hypothesis, there remains a good deal to be done in regards to research for RA treatments. There are many competing hypotheses about the mechanisms of pregnancy induced immune protection, and some have found similar evidence for their theories. These would have to be tested, as would this study, for repeatable results in mouse models and eventually in human cases. If this were to be geared toward a clinical approach and possible therapeutic agents there are many more steps, and safety precautions, that have to be taken. Additionally there is a question that the authors point toward of what could be the “evolutionary advantage” of this pregnancy protection was it designed, or accidental? This field is still open and many advances should be made… stay tuned!
Munoz-Suano A, Kallikourdis M, Sarris M, Betz A. (2011). Regulatory t Cells protect from autoimmune arthritis during pregnancy. Journal of Autoimmunity. (doi:10.1016/j.jaut.2011.09.007)
1. “Rheumatoid Arthritis” Mayo Clinic. 2 Nov. 2011 <http://www.mayoclinic.com/health/rheumatoid- arthritis/DS00020>
2. Østensen M and Villiger P M. (2007) The remission of rheumatoid arthritis during pregnancy. Seminars in Immunopathology. 29: 185-191, (DOI: 10.1007/s00281-007-0072-5)
3. Temprano, Katherine. “Effects of Pregnancy on Rheumatoid Arthritis” Medscape Reference. 31 May 2011 <http://emedicine.medscape.com/article/335186-overview>
4. Russell AS, Johnston C, Chew C, Maksymowych WP (1997). Evidence for reduced Th1 function in a normal pregnancy: a hypothesis for the remission of rheumatoid arthritis. The Journal of Rheumatology. 24: 1045-1050. <http://ukpmc.ac.uk/abstract/MED/9195507>