Effects of anti-phospholipid antibodies on a human trophoblast cell line (HTR-8/SVneo)

Jovanović, Milica; Božić, Milica; Kovacevic, Tamara; Radojčić, Ljiljana; Petronijević, Miloš; Vićovac, Ljiljana

doi:10.1016/j.acthis.2008.07.001

Cited by 17 publications

(17 citation statements)

References 25 publications

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“…During the differentiation of trophoblastic cells, the EVT invades maternal capillaries and the effects of aPL on this cell type have been well described [12][13][14][15][16]. The ST, which bathes directly in maternal blood, will form a protection between mother and fetus during the entire pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies

Marchetti

Ruffatti

Wuillemin

et al. 2014

Journal of Thrombosis and Haemostasis

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Summary. Background: Obstetric antiphospholipid syndrome (APS) is defined by pregnancy complications associated with antiphospholipid antibodies (aPL). The mechanisms of the pathogenic effects of aPL in pregnancy are poorly understood. Toll-like receptors (TLR) have been implicated previously in APS. Objectives: The aims of our study were (1) to determine aPL effects on trophoblastic cell fusion and differentiation, (2) to identify which TLR is involved in this process, and (3) to evaluate the efficacy of hydroxychloroquine (HCQ) to counteract the effects of aPL. Methods: BeWo cells are a model for trophoblast fusion and differentiation. Fusion index was assessed by immunocytochemical examination, and biochemical differentiation by using ELISA-measured b-human choronic gonadotropin hormone (b-hCG) secretion. We used three types of aPL to study their effect on cell fusion and differentiation: aPL derived from obstetric APS patients and affinity purified and polyclonal rabbit anti-b2-glycoprotein-1 (anti-b2GP1) antibodies. Experiments on fusion were confirmed using primary cytotrophoblastic cells. Results: All of the types of aPL used decreased the fusion index in BeWo and primary trophoblastic cells (64%, 52%, and 41% for BeWo cells and 67% and 62% for primary cells, respectively), and anti-b2GP1 antibodies decreased hCG secretion in BeWo cells (41%). To block TLR4 antibodies or to abolish TLR4 cell surface expression restored fusion index in both cell types and b-human choronic gonadotropin hormone excretion in BeWo cells. HCQ treatment induced the same effect and decreased TLR4 mRNA (40% and 35%, respectively) and protein expressions (62% and 42%, respectively) in BeWo cells. Conclusion: Anti-b2GP1 antibodies decrease trophoblastic differentiation via TLR4. This effect is restored by HCQ, suggesting its therapeutic interest in APS pregnancies.

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Section: Discussionmentioning

confidence: 99%

Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies

Marchetti

Ruffatti

Wuillemin

et al. 2014

Journal of Thrombosis and Haemostasis

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“…The inhibitory effects of APS-IgG upon the invasion of trophoblast cells in-vitro are well-documented 13,18–20. The mechanisms underlying these inhibitory effects are likely to be complex and are not fully understood.…”

Section: Discussionmentioning

confidence: 99%

“…examined the same cohort of ( n = 6) VT+/PM− patients with three live births from six pregnancies and ( n = 6) VT−/PM+ patients with six live births from 22 pregnancies; Bose et al 19. examined ( n = 3) LA-positive patients with recurrent miscarriage with a mean number of live births of 0.3 (range 0–1) from a mean number of first-trimester miscarriages was 4.2 (range 3–8) and ( n = 3) control human sera with an undisclosed number of pregnancies; Jovanovic et al 20. examined ( n = 13) patients with APS and ( n = 10) control human sera with an undisclosed number of pregnancies; and Mulla et al 22.…”

Section: Discussionmentioning

confidence: 99%

Purified IgG from Patients with Obstetric but not IgG from Non‐obstetric Antiphospholipid Syndrome Inhibit Trophoblast Invasion

Poulton

Ripoll

Pericleous

et al. 2014

American J Rep Immunol

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ProblemSome patients with antiphospholipid syndrome (APS) suffer pregnancy morbidity (PM) but not vascular thrombosis (VT), whilst others suffer VT only. Therefore, we compared the effects of IgG from VT+/PM− and VT−/PM+ subjects on human first-trimester trophoblast (HTR8) cells.Method of studyHTR-8 cells were incubated with APS VT+/PM−, APS VT−/PM+ or healthy control (HC) IgG. We measured trophoblast invasion by cell invasion assay; mRNA expression of TLR4 and adaptor proteins; phosphorylation of p38 MAPK, NFκB and ERK; and expression of interleukin (IL)-8 and IL-6.ResultsVT−/PM+ IgG, but not VT+/PM− IgG significantly reduced HTR-8 invasion. The effects on invasion were blocked by TLR-4 inhibition. Neither VT+/PM− nor VT−/PM+ IgG altered MyD88 mRNA expression, phosphorylation of signalling molecules or cytokine expression.ConclusionsVT−/PM+ IgG exert functionally relevant effects on human trophoblast cells but VT+/PM− IgG do not.

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“…aPL has been shown to prevent HTR-8, a trophoblastic cell line, from invading on matrigel assay and to decrease integrins proteic expressions [55]. …”

Section: Pathogenesis Of Apl During Pregnancymentioning

confidence: 99%

Obstetrical Antiphospholipid Syndrome: From the Pathogenesis to the Clinical and Therapeutic Implications

Marchetti

Cohen

Moerloose

2013

Clinical and Developmental Immunology

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Antiphospholipid syndrome (APS) is an acquired thrombophilia with clinical manifestations associated with the presence of antiphospholipid antibodies (aPL) in patient plasma. Obstetrical APS is a complex entity that may affect both mother and fetus throughout the entire pregnancy with high morbidity. Clinical complications are as various as recurrent fetal losses, stillbirth, intrauterine growth restriction (IUGR), and preeclampsia. Pathogenesis of aPL targets trophoblastic cells directly, mainly via proapoptotic, proinflammatory mechanisms, and uncontrolled immunomodulatory responses. Actual first-line treatment is limited to low-dose aspirin (LDA) and low-molecular weight heparin (LMWH) and still failed in 30% of the cases. APS pregnancies should be a major field in obstetrical research, and new therapeutics are still in progress.

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Effects of anti-phospholipid antibodies on a human trophoblast cell line (HTR-8/SVneo)

Cited by 17 publications

References 25 publications

Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies

Hydroxychloroquine restores trophoblast fusion affected by antiphospholipid antibodies

Purified IgG from Patients with Obstetric but not IgG from Non‐obstetric Antiphospholipid Syndrome Inhibit Trophoblast Invasion

Obstetrical Antiphospholipid Syndrome: From the Pathogenesis to the Clinical and Therapeutic Implications

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