Malaria drug helps prevent complications in pregnant lupus patients
An anti-malaria drug combination might be useful in helping to prevent pregnancy complications in women with lupus and the related disorder antiphospholipid syndrome.
Circulating antibodies, called antiphospholipid antibodies, are normally produced by the body to recognize and attack bacteria and other microbes.
In those women with lupus and/or antiphospholipid syndrome, however, these antibodies recognize and attack the body’s own proteins, putting women at high risk for recurrent pregnancy loss and late gestational complications, such as preeclampsia.
Yale School of Medicine researchers have published their new study in the American Journal of Reproductive Immunology.
Patients with lupus or antiphospholipid syndrome are often treated with the anti-malarial drug hydroxychloroquine. While the drug can be safely continued during pregnancy, it was unknown whether it might be beneficial in preventing pregnancy complications in women with lupus and/or antiphospholipid syndrome.
In the study, senior author Vikki M. Abrahams, associate professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale, along with first author and Yale medical student Caroline Albert, measured possible detrimental effects of antiphospholipid antibodies on human placental trophoblast cell function.
“We found that hydroxychloroquine partially reversed some, but not all, of the detrimental effects of antiphospholipid antibodies on human placental cell function.
"So perhaps some form of combination therapy that includes hydroxychloroquine may be beneficial to pregnant patients with lupus and/or antiphospholipid syndrome.”
Vikki M. Abrahams, associate professor, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University
Women with antiphospholipid syndrome (APS) are at risk for pregnancy complications. Antiphospholipid antibodies (aPL) alter trophoblast function by triggering an inflammatory cytokine response; modulating angiogenic factor secretion; and inhibiting migration. While patients with APS are often treated with hydroxychloroquine (HCQ), its effect on trophoblast function is poorly understood.
Method of study
A human first trimester trophoblast cell line was treated with or without antihuman β2GPI mAbs in the presence or absence of HCQ. Supernatants were analyzed by ELISA. Cell migration was measured using a colormetric assay.
Antiphospholipid antibodies-induced trophoblast IL-8, IL-1 β, PlGF, and sEndoglin secretion were not altered by HCQ. aPL-induced inhibition of trophoblast migration was partially reversed by HCQ, even though HCQ significantly increased secretion of pro-migratory IL-6 to greater than baseline. aPL-induced upregulation of TIMP2 appears to inhibit trophoblast migration; the inability of HCQ to prevent aPL-induced TIMP2 may explain why migration was only partially restored.
Hydroxychloroquine reversed the aPL-inhibition of trophoblast IL-6 secretion and partially limited aPL-inhibition of cell migration. Thus, some form of combination therapy that includes HCQ may be beneficial to pregnant APS patients.
Other authors on the study include William J. Schlesinger, Chez A. Viall, Melissa J. Mulla, Jan J. Brosens, and Lawrence W. Chamley.
The study was funded by grants from the Lupus Foundation of America and the March of Dimes. Caroline Albert was supported by the 2012 Lupus Foundation of America Gina M. Finzi Memorial Student Summer Fellowship.
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