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Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases?

Nature Reviews Rheumatology volume 14, pages 433–440 (2018)Cite this article

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Abstract

Recurrent thrombosis and miscarriages are the main clinical manifestations of antiphospholipid syndrome (APS). Although most patients display both clinical signs, some patients can have isolated vascular or obstetric variants. Emerging data raise the question of whether obstetric and vascular APS are the same or different diseases. An important difference between the two conditions is that a thrombophilic state is a common feature in vascular APS, whereas clot occlusions of the decidual spiral arteries are seldom observed in obstetric APS, and infarctions are found in only one-third of APS placentae. Conversely, inflammation, which is undetectable in vascular APS, is frequently observed in the placentae of patients with obstetric APS and has been documented in the placentae of pregnant mice with fetal loss mediated by antiphospholipid antibodies. Attempts to identify different antibodies or epitopes responsible for the two clinical manifestations of APS have so far been unsuccessful. Possible mechanisms exist that might explain the development of the two clinical presentations, including the tissue distribution and expression level of the main target antigen of antiphospholipid antibodies, β2 glycoprotein I (β2GPI). The identification of the factors that promote the onset of either obstetric or vascular APS has important diagnostic and therapeutic implications.

Key points

  • There are two main clinical variants of antiphospholipid syndrome (APS): vascular and obstetric APS.

  • Although most patients with APS have both vascular and obstetric manifestations, isolated vascular or obstetric variants exist.

  • Thrombosis represents the main clinical manifestation of vascular APS, whereas obstetric APS is characterized by pregnancy morbidity including miscarriage, unexplained fetal death and premature birth.

  • Defective placentation is the major cause of pregnancy morbidity in APS; non-thrombotic mechanisms might be more important than placental infarction in the pathogenesis of obstetric APS.

  • β2 glycoprotein I (β2GPI)-dependent antiphospholipid antibodies are currently considered the main pathogenic autoantibodies in APS.

  • Whether the same antibodies can induce both vascular thrombosis and pregnancy morbidity is still unclear.

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Fig. 1: Potential pathogenic mechanisms mediated by β2GPI-dependent aPL in the placenta.
Fig. 2: Potential pathogenic mechanisms mediated by β2GPI-dependent aPL in blood vessels.

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Acknowledgements

The work of P.L.M. and F.T. is supported by funding from the Ricerca Corrente Istituto Auxologico Italiano.

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Authors and Affiliations

  1. Immunorheumatology Research Laboratory, Istituto Auxologico Italiano, Milan, Italy

    Pier Luigi Meroni, Maria Orietta Borghi, Claudia Grossi, Cecilia Beatrice Chighizola & Francesco Tedesco

  2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy

    Maria Orietta Borghi & Cecilia Beatrice Chighizola

  3. Department of Life Sciences, University of Trieste, Trieste, Italy

    Paolo Durigutto

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P.D. researched data for the article. All authors wrote the article and reviewed and/or edited the article before submission. P.L.M., M.O.B., C.G., C.B.C. and F.T. provided substantial contributions to discussions of the content.

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Correspondence to Pier Luigi Meroni.

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Glossary

Pregnancy morbidity

One or more unexplained deaths of a morphologically normal fetus at or beyond the tenth week of gestation; one or more premature births of a morphologically normal neonate before the thirty-fourth week of gestation because of eclampsia, severe pre-eclampsia or placental insufficiency; or three or more unexplained consecutive spontaneous abortions (miscarriages) before the tenth week of gestation.

Placentation

The formation, type and structure or arrangement of the placenta.

Trophoblasts

Cells that form the outer layer of a blastocyst, which provide the embryo with nutrients and later develop into a large part of the placenta; these cells proliferate and differentiate into two cell layers: cytotrophoblasts and syncytiotrophoblasts.

Syncytiotrophoblasts

Epithelial cells that make up a continuous, thick layer that covers the embryonic placental villi and are in direct contact with maternal blood; this layer secretes human chorionic gonadotropin hormone in order to maintain progesterone secretion and sustain a pregnancy.

Extravillous trophoblasts

Cells that are a result of differentiation of cytotrophoblasts at the tip of placental villi; extravillous trophoblasts invade the uterine spiral arteries, initially forming plugs that partially or fully occlude the lumens of spiral arteries, and later transform the spiral arteries into large-bore, non-vasoactive vessels that maximize maternal blood supply to the placenta.

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Meroni, P.L., Borghi, M.O., Grossi, C. et al. Obstetric and vascular antiphospholipid syndrome: same antibodies but different diseases?. Nat Rev Rheumatol 14, 433–440 (2018). https://doi.org/10.1038/s41584-018-0032-6

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