Hydroxychloroquine protects against placental injury in obstetric antiphospholipid syndrome

Obstetric antiphospholipid syndrome (OAPS) is mediated by antiphospholipid antibodies (aPLs, anti-β2 glycoprotein I antibody is the main causative antibody), and placental diseases such as recurrent miscarriage, pre-eclampsia, and fetal growth restriction are the main clinical features
of placental pathological pregnancy.
It is a disease
that seriously threatens the health of pregnant women.
Originally used as an antimalarial agent, hydroxychloroquine (HCQ) now shows benefit in refractory OAPS where conventional treatment has failed, promising protective clinical benefits
for both mother and fetus.

HCQ has been shown to reduce aPLs titers in plasma
in primary or secondary antiphospholipid syndromes.
Prenatal exposure to HCQ in anti-SSA/SSB seropositive patients reduces the risk of
fetal cardiac manifestations in neonatal lupus.

However, its efficacy and mechanism of action are unclear
.
Therefore, the investigators systematically evaluated the effects of anti-β2GP1 antibodies on trophoblast cell function and investigated the effects of
HCQ in vivo and in vitro.
To determine whether HCQ can reverse adverse effects of antibodies on multiple trophoblast functions and whether HCQ plays a key role
in the pathogenesis of adverse pregnancy and fetal outcomes.

OAPS placental pattern diagram for HCQ-treated:

Therapeutic effects of HCQ in APS animal models:

After collecting clinical data to determine the therapeutic effect, human trophoblast cells in the first trimester of pregnancy were prepared and treated
with aPL.
After HCQ addition, the proliferation, invasion, migration and tubule formation of trophoblast cells were observed to determine the therapeutic mechanism
of HCQ on trophoblast cells.
By establishing a mouse model of obstetric APS similar to the clinical situation, the therapeutic effect
of HCQ on pathological pregnancy can be tested.
The normal function of trophoblast cells is affected
by aPL.
Antibodies reduce the ability of trophoblast cells to invade and migrate and may impair tubule formation, which is closely related to
placental insufficiency.
HCQ can partially reverse these side effects
.
In an OAPS mouse model, the researchers found that HCQ prevented fetal death and reduced the incidence
of pathological pregnancies.

Thus, HCQ can improve pregnancy outcomes and reverse aPL inhibition
of trophoblast disease.
In OAPS, the use of
HCQ needs to be carefully considered.
The mechanism of HCQ can provide new ideas and treatment options
for placental diseases caused by immune dysfunction.

HCQ reduces fetal absorption and placental abnormalities in OAPS:

References:

Liu J, Zhang L, Tian Y, Wan S, Hu M, Song S, Zhang M, Zhou Q, Xia Y, Wang X.
Protection by hydroxychloroquine prevents placental injury in obstetric antiphospholipid syndrome.
J Cell Mol Med.
2022 Aug; 26(15):4357-4370.
doi: 10.
1111/jcmm.
17459.
Epub 2022 Jun 29.
PMID: 35770338; PMCID: PMC9344817.