“But there was more to know. When I tell a woman that she has lupus, one of her first questions is, ‘Doctor, will I be able to have children?’ For many years, we thought that pregnancy caused lupus to flare and should be avoided. This recommendation, however, was not based on strong data, and we knew that some women with lupus had uncomplicated pregnancies, while others had miscarriages or preeclampsia.
“To understand the mechanism of pregnancy failure in lupus, we developed a model of the disease in mice. It was a new area for me, and, perhaps because I approached it without a bias, I could test and prove a hypothesis that challenged long-held dogma. We showed that inflammation, particularly complement activation (and not thrombosis), was a key mediator of poor pregnancy outcome in APL-treated mice. We also found that drugs that block complement could prevent fetal death, growth restriction and preeclampsia in mice.
“But, of course, the ultimate goal of the mice experiments was to help patients. The first step in applying our findings to lupus patients was to identify those destined for poor pregnancy outcome. Lupus is not a common disease. Pregnant lupus patients are less common, and those willing to participate in studies, even harder to come by. Moreover, we had to convince the NIH that a large, multicenter study, expensive study was likely to yield markers that predicted outcome. Here, I was fortunate that foundations (Alliance for Lupus Research) and individual donors—most generously Kit and Arnie Snider who funded the MKCLC at HSS—supported preliminary studies that made possible a compelling proposal, one that was awarded federal funding. I must thank Susana Serrate-Sztein of NIAMS, a dedicated and visionary steward of the public trust, for believing in us and helping us gain permission to submit what some could have been construed as an audacious proposal to NIAMS.
“The PROMISSE study has exceeded my expectations for success in enrolling patients and generating important new information. Over 11 years of funding, $14 million all told, we studied 755 pregnant patients monthly. They were recruited at eight centers in the U.S. and Canada, and from them, we collected nearly a quarter-million samples. Ours is the largest prospective study of lupus pregnancies.
“PROMISSE taught us that pregnancy in lupus patients with quiescent disease is safe. This reassuring finding will enable physicians to counsel patients about how to time pregnancy. PROMISSE also allowed us to identify biomarkers that, early in pregnancy, predict life-threatening complications for mother and fetus.