Early human pregnancy serum cytokine levels predict autoimmunity in offspring

Abstract

It is generally believed that pregnancy is mediated by a Th2 response, which includes cytokines that promote placental growth and are involved in inducing tolerance to the foetus. If the balance between Th1/and Th2-mediated cytokines is disrupted, systemic and local changes could predispose the foetus to future disease. Therefore, a shift in the Th1/Th2 balance during pregnancy, possibly caused by underlying environmental factors, could be associated with post-partum autoimmune disease in the offspring. Based on this presumption, we used celiac disease as a model to investigate whether autoimmunity is triggered in the foetus during early pregnancy, observed as changes in the mother's cytokine profile. Ten cytokines were measured by electro-chemi-luminescent multiplex ELISA in serum samples obtained from mothers during early pregnancy. Cases included women with children who had developed verified celiac disease before the age of 5, who were compared with other women as matched controls. We observed that 7 out of 10 cytokine levels were significantly increased in our case mothers when compared to controls. Five of these belonged to what is generally known as a Th1-mediated response (TNFα, IFNγ, IL-2, IL-1β and IL-12) and two were Th2 cytokines (IL-13 and IL-10). However, the IL-10 cytokine is known to have features from both arms of the immune system. These results were confirmed in a logistic regression model where five out of the initial seven cytokines remained. This study suggests that increase in Th1 serum cytokines may be associated with celiac disease in offspring.

Keywords::

• Autoimmunity
• human
• pregnancy
• cytokines
• Th1/Th2 response

Acknowledgements

We would like to thank the DiPiS and CiPiS study group as well as the Southern Sweden Microbiological Biobank (SSM-Biobank) with Professor Joakim Dillner. We would also like to thank Aline Marshall and Kia Sjölin for their technical assistance. No potential conflicts of interest relevant to this article were reported.

Declaration of interest: The present study was supported by European Foundation for the Study of Diabetes (EFSD), the Novo Nordisk Foundation, the Swedish Society of Medicine and the Krapperup foundation. Our thanks go to the Region Skåne County Council for Research and Development for its financial support. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.