Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) affects 1-2 % of couples who are trying to conceive. At some point, some couples do maintain a healthy pregnancy to term, but the underlying mechanism of RPL remains elusive. Human leukocyte antigen (HLA)-G is an immune modulatory molecule. Our group previously showed increased HLA-G levels in the decidua of term pregnancies after RPL, while other studies showed reduced soluble HLA-G (sHLA-G) blood levels in women with RPL. This led us to investigate sHLA-G levels in blood of women with RPL who had either a subsequent pregnancy loss (RPL-pregnancy loss) or a healthy term pregnancy (RPL-live birth), and compare these to healthy control pregnancies and non-pregnant controls. Soluble HLA-G concentrations were quantified by ELISA. Women with healthy term pregnancy had increased sHLA-G levels compared to non-pregnant controls. In contrast, RPL-live birth women at term did not have increased blood sHLA-G levels. Soluble HLA-G levels remained stable between first and third trimester. Interestingly, when comparing first trimester samples of RPL-live birth to RPL-pregnancy loss, sHLA-G levels also did not significantly differ. High sHLA-G levels in blood seem not to be crucial for an ongoing healthy pregnancy after RPL. However, since it was previously shown that women with RPL-live birth have increased HLA-G levels in term decidua compared to control pregnancies, the current data suggest that local and systemic immune regulation are not necessarily in concert. Further study of the contribution of fetus-derived HLA-G and HLA-G of maternal origin may provide more insight in the pathophysiology of RPL.