Background/Purpose:  The increased rates of preeclampsia, preterm birth, and intrauterine growth restriction in SLE pregnancy are only partially explained by the vascular effects of anti-phospholipid antibodies.  SLE patients themselves are born preterm more often than expected, suggesting a heritable defect in maternal-fetal tolerance.  PD-L1 is one candidate gene, in that it has been implicated in the both autoimmunity and maternal-fetal tolerance:  PD-L1 is expressed on healthy antigen presenting cells to downregulate inflammatory responses, and also on placental trophoblasts at the maternal-fetal interface, where it inhibits alloreactive T cells.  Peripheral blood antigen presenting cells from SLE patients are deficient in PD-L1 expression compared to remission or healthy controls.  Little is known about placental costimulatory molecules in women with autoimmune diseases.  This study tested the hypothesis that placental PD-L1 expression is abnormally regulated in SLE pregnancy.

Methods:  Expression of PD-L1 was quantified by immunohistochemistry in placentas from full-term pregnancies of 4 SLE patients, 7 rheumatoid arthritis patients (RA) and 11 healthy control women obtained from the Global Alliance for the Prevention of Prematurity and Stillbirth Repository.  PD-L1 mRNA expression was assayed by RT-PCR and normalized to GAPDH expression.  PD-L1 on peripheral CD14+/CD11c+ monocytes was assayed by flow cytometry. Significant differences between groups were tested by T-test.

Results:  By immunostaining, PD-L1 expression in SLE placentas was significantly reduced compared to control groups.  The difference was most pronounced on the fetal side of the placenta.  PD-L1 mRNA expression correlated with protein expression, although the differences were not significant.  On peripheral blood monocytes, PD-L1 expression was low in juvenile SLE patients compared to healthy controls (55% of SLE monocytes v. 93% of healthy monocytes, p=0.001). Although in the normal range, mothers of SLE patients also had relatively low PD-L1 expression compared to control mothers (87% v. 94%, p=0.04).

Table 1.  Relative median PD-L1 expression in the placenta in patients and controls.

     *SLE versus controls; **RA versus controls.

Conclusion:  PD-L1 expression is dysregulated in pregnant women with SLE (in placenta), in SLE patients, and in mothers of SLE patients (in blood).  Inadequate expression of PDL-1 in the placentas of patients with SLE could result in loss of maternal-fetal tolerance, contributing to the high rate of pregnancy complications in SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreased-programmed-death-ligand-1-pd-l1-in-systemic-lupus-erythematosus-sle-placenta/