Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia

Wedenoja, Satu; Yoshihara, Masahito; Teder, Hindrek; Sariola, Hannu; Gissler, Mika; Katayama, Shintaro; Wedenoja, Juho; Häkkinen, Inka M. K.; Ezer, Sini; Linder, Nina; Lundin, Johan; Skoog, Tiina; Sahlin, Ellika; Iwarsson, Erik; Pettersson, Karin; Kajantie, Eero; Mökkönen, Mikael; Heinonen, Seppo; Laivuori, Hannele; Krjutškov, Kaarel; Kere, Juha

doi:10.1016/j.ebiom.2020.102872

Cited by 28 publications

(19 citation statements)

References 115 publications

(155 reference statements)

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“…A separate report showed that both uterine and peripheral NK cells expressed KIR2DL1A and KIR2DL1B , with a predominance of KIR2DL1A variants being associated with enhanced NK‐cell function as well as an increased risk for preeclampsia 181 . In line with these findings, the expression of the immune tolerance‐promoting HLA‐G 127,128 and its receptors, such as LILRB1, 182 was decreased in placentas from women with preeclampsia 183 . A link between fetal HLA genotype and maternal preeclampsia risk was further supported by the reported association between a poly‐T stretch within the downstream region of the HLA‐G*01:01:01:01 allele and the occurrence of preeclampsia 184 .…”

Section: Introductionmentioning

confidence: 78%

“…181 In line with these findings, the expression of the immune tolerance-promoting HLA-G 127,128 and its receptors, such as LILRB1, 182 was decreased in placentas from women with preeclampsia. 183 A link between fetal HLA genotype and maternal preeclampsia risk was further supported by the reported association between a poly-T stretch within the downstream region of the HLA-G*01:01:01:01 allele and the occurrence of preeclampsia. 184 Based on these observations, the determination of local NK-cell status in early pregnancy (e.g.…”

Section: Natural Killer Cellsmentioning

confidence: 88%

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Cellular immune responses in the pathophysiology of preeclampsia

Miller

Motomura

Galaz

et al. 2021

Journal of Leukocyte Biology

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Preeclampsia, defined as new‐onset hypertension accompanied by proteinuria occurring at 20 weeks of gestation or later, is a leading cause of perinatal morbidity and mortality worldwide. The pathophysiology of this major multi‐systemic syndrome includes defective deep placentation, oxidative stress, endothelial dysfunction, the presence of an anti‐angiogenic state, and intravascular inflammation, among others. In this review, we provide a comprehensive overview of the cellular immune responses involved in the pathogenesis of preeclampsia. Specifically, we summarize the role of innate and adaptive immune cells in the maternal circulation, reproductive tissues, and at the maternal‐fetal interface of women affected by this pregnancy complication. The major cellular subsets involved in the pathogenesis of preeclampsia are regulatory T cells, effector T cells, NK cells, monocytes, macrophages, and neutrophils. We also summarize the literature on those immune cells that have been less characterized in this clinical condition, such as γδ T cells, invariant natural killer T cells, dendritic cells, mast cells, and B cells. Moreover, we discuss in vivo studies utilizing a variety of animal models of preeclampsia to further support the role of immune cells in this disease. Finally, we highlight the existing gaps in knowledge of the immunobiology of preeclampsia that require further investigation. The goal of this review is to promote translational research leading to clinically relevant strategies that can improve adverse perinatal outcomes resulting from the obstetrical syndrome of preeclampsia.

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Section: Introductionmentioning

confidence: 78%

Section: Natural Killer Cellsmentioning

confidence: 88%

Cellular immune responses in the pathophysiology of preeclampsia

Miller

Motomura

Galaz

et al. 2021

Journal of Leukocyte Biology

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“…Although the etiology of PE remains unclear, multiple immune mechanisms have been proposed to play a role, as the placenta constitutes a unique immune environment. Differentially expressed levels of fetal Human Leukocyte Antigen (HLA), especially HLA-G ( 26 – 28 ), immune cell influx ( 29 ) and cytokine expression ( 30 ) have been reported in preeclamptic placentas. Complement has also been implicated in the development of PE.…”

Section: Discussionmentioning

confidence: 99%

Circulating Levels of Anti-C1q and Anti-Factor H Autoantibodies and Their Targets in Normal Pregnancy and Preeclampsia

et al. 2022

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Preeclampsia (PE) generally manifests in the second half of pregnancy with hypertension and proteinuria. The understanding of the origin and mechanism behind PE is incomplete, although there is clearly an immune component to this disorder. The placenta constitutes a complicated immune interface between fetal and maternal cells, where regulation and tolerance are key. Stress factors from placental dysfunction in PE are released to the maternal circulation evoking the maternal response. Several complement factors play a role within this intricate landscape, including C1q in vascular remodeling and Factor H (FH) as the key regulator of alternative pathway complement activation. We hypothesize that decreased levels of C1q or FH, or disturbance of their function by autoantibodies, may be associated with PE. Autoantibodies against C1q and FH and the concentrations of C1q and FH were measured by ELISA in maternal sera from women with preeclamptic and normal pregnancies. Samples originated from cohorts collected in the Netherlands (n=63 PE; n=174 control pregnancies, n=51 nonpregnant), Finland (n=181 PE; n=63 control pregnancies) and Norway (n=59 PE; n=27 control pregnancies). Serum C1q and FH concentrations were higher in control pregnancy than in nonpregnant women. No significant differences were observed for serum C1q between preeclamptic and control pregnancy in any of the three cohorts. Serum levels of FH were lower in preeclamptic pregnancies compared to control pregnancies in two of the cohorts, this effect was driven by the early onset PE cases. Neither anti-C1q autoantibodies nor anti-FH autoantibodies levels differed between women with PE and normal pregnancies. In conclusion, levels of anti-C1q and anti-FH autoantibodies are not increased in PE. C1q and FH are increased in pregnancy, but importantly, a decrease in FH concentration is associated with PE.

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“…In colorectal carcinoma (CRC), HLA‐G expression might correlate with tumor‐node‐metastasis (TNM) stage 5 but data on its effects on the overall survival remain conflicting 2,6–14 . We aimed to study HLA‐G protein expression using a large tissue microarray series of CRC tumors ( n = 317) and immunohistochemistry optimized for placental staining of HLA‐G 15 . We further assessed HLA‐G immunostaining in relation with clinical parameters associated with progressive disease and cluster of differentiation 3 (CD3) positive tumor infiltrating lymphocytes.…”

Section: Figurementioning

confidence: 99%

HLA‐G expression correlates with histological grade but not with prognosis in colorectal carcinoma

Kaprio

Sariola

Linder

et al. 2021

HLA

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Trophoblast‐specific expression of HLA‐G induces immune tolerance for the developing fetus. Pathological HLA‐G expression later in life might contribute to immune escape of various cancers. We studied the still controversial role of HLA‐G in colorectal carcinoma (CRC) using the MEM‐G/1 antibody and a tissue microarray series of CRC tumors (n = 317). HLA‐G expression appeared in 20% of the tumors and showed high intratumoral heterogeneity. HLA‐G positivity was associated with better differentiation (p = 0.002) and non‐mucinous histology (p = 0.008). However, HLA‐G expression alone showed no prognostic value: 5‐years disease‐specific survival among patients with HLA‐G expression was 68.9% (95% CI: 62.7%–75.0%) compared to 74.8% (95% CI: 63.2%–86.3%) among those without expression. These results support a modulatory role of HLA‐G in CRC.

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Fetal HLA-G mediated immune tolerance and interferon response in preeclampsia

Cited by 28 publications

References 115 publications

Cellular immune responses in the pathophysiology of preeclampsia

Cellular immune responses in the pathophysiology of preeclampsia

Circulating Levels of Anti-C1q and Anti-Factor H Autoantibodies and Their Targets in Normal Pregnancy and Preeclampsia

HLA‐G expression correlates with histological grade but not with prognosis in colorectal carcinoma

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