Gene Changes Key to Successful Pregnancy in Lupus
Gene Changes Key to Successful Pregnancy in Lupus

April 29, 2019

Pregnant women with lupus are more likely to suffer complications than those who don’t. Lupus Research Alliance Scientific Advisory Board members
Dr. Virginia Pascual, Professor at Weill Cornell Medicine; and Dr. Jane Salmon, Collette Kean Research Professor  at Hospital for Special Surgery, and their colleagues asked if testing the blood, of pregnant women with lupus, using advanced technologies could identify, early in pregnancy, lupus patients at high risk for complications.  Their new paper in the Journal of Experimental Medicine shows that during uncomplicated pregnancy in both healthy and lupus women some genes that incite the immune system become less active. These changes may make the immune system less aggressive and reduce the odds that it will attack the fetus. However, women with lupus who had pregnancy complications, including preeclampsia, did not show the desirable decrease in these immune signatures.

Doctors came up with the term “lupus” because they thought the disease’s skin inflammation looked liked a wolf’s bite.  The study “supports the idea that in some cases, pregnancy can ‘tame the wolf.’” Drs. Timothy Niewold and Shilpi Mehta-Lee wrote in a commentary on the paper. They note that the findings may enable doctors to identify patients with lupus who are susceptible to pregnancy complications and need careful monitoring

To the immune system, a fetus developing in the womb resembles a foreign invader. Normally during pregnancy, the mother’s immune system develops what researchers call tolerance and avoids attacking the fetus. But when patients with lupus become pregnant, their immune system may be less likely to develop tolerance to the fetus, leading to complications such as preeclampsia, premature birth, and even death of the fetus.

In the new study, Dr. Pascual and colleagues compared 92 pregnant women with lupus to 43 pregnant women who didn’t have the disease. The researchers obtained blood samples from the women during and shortly after their pregnancies. To detect the earliest changes associated with pregnancy onset, the scientists also analyzed blood from patients undergoing assisted reproductive technology. The researchers evaluated the patients’ immune system by measuring the activity of different genes that help determine how strongly it responds to potential threats. For a subset of these study participants, the investigators also examined the types of cells that are producing the specific immune responses.

Early in pregnancy, the activity of key genes decreased in women who didn’t have lupus, probably increasing their tolerance to the developing baby. The researchers saw similar changes in women with lupus who had successful pregnancies. However, the immune system of women with lupus who went on to develop complications was not turned down. Their immune system might be more likely to attack the fetus or prevent its proper development. This inability to turn down the immune activity appears to be a risk factor for adverse pregnancy outcomes in lupus.

Testing for these changes in gene activity might pinpoint patients with lupus who are more likely to develop pregnancy complications and who needs careful monitoring and specific therapeutic intervention to improve the outcome.

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