The immune system of pregnant women becomes altered to tolerate fetal antigens while still being able to fight infections, and these immunomodulatory consequences influence autoimmune rheumatic diseases. For example, many pregnant patients with rheumatoid arthritis (RA) experience disease improvement, whereas those with ankylosing spondylitis (AS) often experience persistently active disease. Manuela Tham, Department of Rheumatology, Immunology, and Allergology, University Hospital, University of Bern, Switzerland, and colleagues sought to improve their understanding of the factors involved in the pregnancy-induced improvement of RA to broaden their understanding of the pathogenic factors that are involved in RA. According to the study authors, γδT cells are of particular interest because they exhibit immunoregulatory traits in pregnant women. They are CD3+ T cells that exhibit traits of the innate and adaptive immune system, and they use their main functions through cytokine release, cytotoxicity, or antigen presentation.
Dr Tham and colleagues investigated whether pregnancy-related changes in disease activity were associated with changes in the quantity and role of γδT cells, and found that disease activity changes in pregnant patients with RA were associated with functional changes in γδT cell subsets. The reduced proinflammatory profile of γδT cells may contribute to the immunomodulation, resulting in the improvement of RA in pregnant patients.
The authors conducted a prospective study of pregnant women with RA (n = 28), AS (n = 21), and who are healthy (n = 23). They also studied 49 nonpregnant, age-matched participants, including 27 women with RA, 10 with AS, and 12 healthy women.
Longitudinal changes in cytokine-positive Vδ1 and Vδ2 cells were analyzed in healthy patients. In patients with RA, the population of tumor necrosis factor alpha (TNFα)-producing Vδ1 cells decreased from the second to third trimester, and increased from the third trimester to postpartum. Dr Tham and colleagues then compared the differences between the pregnant and nonpregnant participants. For pregnant participants, the third trimester was chosen because this stage was associated with clinical changes in disease activity and quantitative changes in γδT cells. The most pronounced difference in TNFα production was between pregnant and nonpregnant patients with RA; pregnant patients with RA also had a lower proportion of TNFα-positive Vδ1 cells compared with nonpregnant patients with RA (P =.04). In addition, pregnant patients with RA had an approximately 5.7-fold lower proportion of TNFα-positive Vδ2 cells compared with nonpregnant patients with RA (P =.001). Nonpregnant patients with RA showed the highest proportions of interferon gamma (IFNγ)-positive Vδ1 and Vδ2 cells, which was significantly different than the median proportions found in the nonpregnant, healthy participants (Vδ1, P = .04; Vδ2, P = .02). Disease activity scores in patients with RA were lower at the third trimester than 8 weeks postpartum (P =.03). Although the pregnant patients received less medication than the nonpregnant control group, inactive disease was commonly seen in pregnant patients with RA, with 58% to 69% of patients with RA showing low disease activity (Disease Activity Score of 28 joints-C-reactive protein scores <3.2). In contrast, disease activity in patients with AS remained unchanged throughout and following pregnancy.
The study authors explained that these results show a reduced γδT cell proinflammatory cytokine profile in pregnant patients with RA compared with nonpregnant patients with RA. This functional modification of γδT cells occurred in pregnant patients with RA (69% of whom had low disease activity), but not in patients with AS, a disease that exhibits ongoing activity. Changes were identified in the Vδ1 and Vδ2 subsets of circulating γδT cells. These functional changes of γδT cells in pregnant patients with RA, which were largely reflected by decreases of TNFα- and IFNγ-positive γδT cells, seem to be the result of an anti-inflammatory setting. Therefore, Dr Tham and colleagues noted that the tolerogenic profile of γδT cells in pregnant patients with RA may contribute to the process of immunomodulation that occurs during pregnancy.
- Tham M, Schlör GR, Yerly D, et al. Reduced pro-inflammatory profile of γδT cells in pregnant patients with rheumatoid arthritis. Arthritis Res Ther. 2016;18:26.