Does pregnancy provide vaccine‐like protection against rheumatoid arthritis?

Abstract

Objective. Previous studies have evaluated the correlation between rheumatoid arthritis (RA) risk and pregnancy history, with conflicting results. Fetal cells acquired during pregnancy provide a potential explanation for modulation of RA risk by pregnancy. The present study was undertaken to examine the effect of parity on RA risk.Methods. We examined parity and RA risk using results from a population-based prospective study in Seattle, Washington and the surrounding area and compared women who were recently diagnosed as having RA (n ‫؍‬ 310) with controls (n ‫؍‬ 1,418). We also evaluated the distribution of parity in cases according to HLA genotype.Results. We found a significant reduction of RA risk associated with parity (relative risk [RR] 0.61 [95% confidence interval 0.43-0.86], P ‫؍‬ 0.005). RA risk reduction in parous women was strongest among those who were younger. Most striking was that RA risk reduction correlated with the time that had elapsed since the last time a woman had given birth. RA risk was lowest among women whose last birth occurred 1-5 years previously (RR 0.29), with risk reduction lessening progressively as the time since the last birth increased (for those 5-15 years since last birth, RR 0.51; for those >15 years, RR 0.76), compared with nulliparous women (P for trend ‫؍‬ 0.007). No correlation was observed between RA risk and either age at the time a woman first gave birth or a woman's total number of births. Among cases with the highest genetic risk of RA (i.e., those with 2 copies of RA-associated HLA alleles), a significant underrepresentation of parous women versus nulliparous women was observed (P ‫؍‬ 0.02).Conclusion. In the present study, there was a significantly lower risk of RA in parous women that was strongly correlated with the time elapsed since a woman had last given birth. While the explanation for our findings is not known, HLA-disparate fetal microchimerism can persist many years after a birth and could confer temporary protection against RA.

Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host?

“…In addition, the reduction in RA risk that is associated with increasing parity is only seen after the first year postpartum. 23 In conclusion, despite a higher number of FMc sources, no significant change in FMc was observed with increasing parity, and increasing parity was associated with a significantly lower concentration of MMc. These observations raise interesting questions about the interaction of acquired grafts within a host, including whether such interactions may ultimately lead to the emergence and persistence of 1 dominant source of Mc, as is seen in dual CBT and which may impact the endurance of the NIMA effect.…”

“…6 Interestingly, some disease states that have been found to vary according to a woman's reproductive history (primarily parity, or number of deliveries) also are associated with altered Mc. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Thus, there exist parallel associations between Mc and disease, and parity and disease. Given the concurrent associations, we sought to answer the question whether parity might alter Mc in such a way as to support the hypothesis of a functional connection between Mc and disease.…”

Peripheral Neuroimmunoendocrine Interactions: Contribution of TNFRp55 to the Circadian Synchronization of Progesterone and Cytokine Production in Joints of Mice in Late Pregnancy

“…However, it has also been reported that there is an increased risk of developing RA or an exacerbation of an already established RA particularly in the first 3–12 months after delivery [26]. Additionally, Guthrie et al [27] also found that a shorter time interval from the last childbirth is strongly and significantly correlated with a reduced RA risk.…”

Maternal–Fetal Cell Trafficking and Microchimerism

“…A significant reduction in risk for the development of new RA is observed for parous compared with nulliparous women, and interestingly, this effect wanes with increasing time from the last birth. While the explanation for these observations is not known, a reasonable explanation is that there is an acquisition of HLA disparate fetal Mc carrying HLA alleles that are protective for RA [6]. However, the fetal Mc that a woman acquires could also carry HLA alleles associated with RA-risk.…”