Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Sep;69(9):1710-1721.
doi: 10.1002/art.40136. Epub 2017 Jul 18.

Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and Pregnancy: Pathogenesis to Translation

Vikki M Abrahams  1 , Lawrence W Chamley  2 , Jane E Salmon  3
Affiliations
Review

Emerging Treatment Models in Rheumatology: Antiphospholipid Syndrome and Pregnancy: Pathogenesis to Translation

Vikki M Abrahams et al. Arthritis Rheumatol. 2017 Sep.
No abstract available

PubMed Disclaimer

Conflict of interest statement

CONFLICT(S) OF INTEREST/DISCLOSURE(S):

Investigator-initiated grant to JES from UCB

Figures

Figure 1
Figure 1. Variations of normal and pathologic remodelling of the spiral arteries
(A) A non-pregnant uterus showing the tightly coiled spiral arteries with musculo-elastic walls that connect, via capillary beds, to the decidual veins, (B) A pregnant uterus in the first trimester where extravillous trophoblasts (EVT; in green) have invaded from the placenta into the spiral arteries and started to remodel the vessels removing the musculo-elastic walls. At this early stage, the invasive trophoblasts form loosely cohesive plugs (TB plugs) that occlude maternal red blood cells but permit the passage of plasma allowing aPL to access the syncytiotrophoblast (STB) and invading cytotrophoblasts. (C) A pregnant uterus at mid-gestation, in a normal pregnancy, with the spiral arteries (there are 30–50 affected arteries) remodelled by invading trophoblasts to 1/3rd of the depth of the myometrium. (D) A uterus at mid-gestation with only partially remodelled spiral arteries that remain tonically active, reducing blood flow to the placenta which leads to preeclampsia (PE) and/or small for gestational age (SGA) fetuses/newborns. (E) A uterus at mid-gestation with very limited remodelling of the spiral arteries with severely reduced volume and increased velocity of blood flow to the placenta, leading to severe placental damage, PE, SGA, and/or stillbirth.
Figure 2
Figure 2
Haematoxylin and eosin stained photomicrograph of the maternofetal interface/implantation site of a first trimester pregnancy showing a spiral artery (outlined by the dotted lines) that is plugged by trophoblasts (green arrows) that have invaded the artery from the placenta (black arrows). The wall of the artery has been removed by the invading trophoblasts. Villi that make up the body of the placenta and float in the maternal blood are completely covered by the syncytiotrophoblast (blue arrows).
Figure 3
Figure 3. Effect of antiphospholipid antibodies on trophoblast cells
Antiphospholipid antibodies (aPL) recognizing beta2 glycoprotein I (β2GPI) expressed by the trophoblast: (A) promotes an anti-angiogenic profile and through apolipoprotein E receptor 2 (ApoER2) reduces cell proliferation and migration; (B) triggers secretion of inflammatory cytokines and chemokines by activating toll-like receptor (TLR) and inflammasome pathways; (C) activates complement on the cell surface leading to neutrophil (PMN) and monocyte activation with release of reactive oxygen species (ROS), TNF-α, anti-angiogenic factors (sFlt1) and tissue factor (TF); and (D) become internalized via low density lipoprotein receptor (LDLR) family members and in turn promote mitochondrial disruption and the deportation of “dangerous” syncytial nuclear aggregates and other microvesicles/exosomes.
See this image and copyright information in PMC

References

    1. Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, PG DEG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS) J Thromb Haemost. 2006;4:295–306. - PubMed
    1. Lockshin MD, Kim M, Laskin CA, Guerra M, Branch DW, Merrill J, Petri M, Porter TF, Sammaritano L, Stephenson MD, Buyon J, Salmon JE. Prediction of adverse pregnancy outcome by the presence of lupus anticoagulant, but not anticardiolipin antibody, in patients with antiphospholipid antibodies. Arthritis Rheum. 2012;64:2311–8. - PMC - PubMed
    1. Saccone G, Berghella V, Maruotti GM, Ghi T, Rizzo G, Simonazzi G, Rizzo N, Facchinetti F, Dall’Asta A, Visentin S, Sarno L, Xodo S, Bernabini D, Monari F, Roman A, Eke AC, Hoxha A, Ruffatti A, Schuit E, Martinelli P group Pw. Antiphospholipid antibody profile based obstetric outcomes of primary antiphospholipid syndrome. The PREGNANTS study. Am J Obstet Gynecol. 2017 - PubMed
    1. Pengo V, Banzato A, Denas G, Jose SP, Bison E, Hoxha A, Ruffatti A. Correct laboratory approach to APS diagnosis and monitoring. Autoimmun Rev. 2013;12:832–4. - PubMed
    1. Cervera R, Piette JC, Font J, Khamashta MA, Shoenfeld Y, Camps MT, Jacobsen S, Lakos G, Tincani A, Kontopoulou-Griva I, Galeazzi M, Meroni PL, Derksen RH, de Groot PG, Gromnica-Ihle E, Baleva M, Mosca M, Bombardieri S, Houssiau F, Gris JC, Quere I, Hachulla E, Vasconcelos C, Roch B, Fernandez-Nebro A, Boffa MC, Hughes GR, Ingelmo M Euro-Phospholipid Project G. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46:1019–27. - PubMed

Publication types

MeSH terms