Preeclampsia, an autoimmune disease

Preeclampsia throws into turmoil 5% to 8% of pregnancies worldwide with potentially terrible consequences. Clinicians who participate in the management of pregnancy should appreciate the evidence revealing that preeclampsia is driven by autoimmunity. The authors of a paper recently published in the Journal of Reporductive Immunology note:

"A basic precondition for the development of preeclampsia is the presence of placental trophoblast cells in the maternal blood circulation. On the other hand, while trophoblast cells are present in the blood of all pregnant women, preeclampsia occurs in only 2–5% of them. Evidently, other factors play a crucial role."

They compared immunological factors including anti-cardiolipin autoantibodies, trophoblast-induced cell-mediated immunity, C3 and C4 complement components, and serum immunoglobulins IgA, IgG, IgM among three groups of women: those with uncomplicated pregnancy, gestational hypertension, or preeclampsia. What did they find?

"In the preeclampsia group, there was a significantly higher number of women positive for anti-cardiolipin autoantibodies, trophoblast-induced cell-mediated immunity was elevated, serum IgG was elevated and C4 complement component was reduced."

In other words the subjects' immune systems were sharply aroused to attack tissue elements specific to pregnancy. The authors summarize their findings:

"We conclude that both elevated autoimmune reactivity and the higher immune reactivity to trophoblast may contribute to the onset of preeclampsia."

The authors of a paper published in Biology of Reproduction discuss the autoimmune instigation of hypertension in preeclampsia:

"Pre-eclampsia is a syndrome characterized by inadequate placentation, which is due to deficient trophoblastic invasion of the uterine spiral arteries. This deficiency can lead to placental hypoxia, secretion of proinflammatory cytokines, and release of angiogenic and antiangiogenic factors. Hypoxic conditions in the placenta can promote oxidative stress and the production of angiogenic factors that are antagonized by soluble receptors, which are also elevated in this syndrome. In addition to these factors, the development of hypertension in women with pre-eclampsia may be associated with the renin-angiotensin system and endothelial dysfunction."

They specifically note the presence of antibodies attacking receptors involved in the regulation of blood pressure:

"The presence of antiangiotensin II type 1 receptor autoantibodies is relevant in pre-eclampsia because it has been related to the secretion of antiangiogenic factors through cytokine pathways, indicating that autoimmune mechanisms may participate in the pathophysiology of this syndrome."

In a fine study published in the journal Hypertension the authors define how a specific B cell subpopulation is a key participant in preeclampsia. They state:

"Preeclampsia is a devastating pregnancy-associated disorder affecting 5% to 8% of pregnant women worldwide. It emerges as an autoimmune-driven disease, and, among others, the autoantibodies against angiotensin type 1 receptor II have been proposed to account for preeclampsia symptoms. Despite much attention focused on describing autoantibodies associated with preeclampsia, there is no clue concerning the cell population producing them. CD19+CD5+ B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures."

They set out to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia. They found that...

"The frequency of CD19+CD5+ cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry."

Interestingly, there was a hormonal component:

"This seems to be driven by the high human chorionic gonadotropin levels present in the serum and placenta supernatant of preeclamptic patients versus normal pregnant women. Not only ≈95% of CD19+CD5+ cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture."

Regarding the link with hypertension in preeclampsia compared to normal pregnancies:

"Most importantly, isolated CD19+CD5+ cells produce autoantibodies against angiotensin type 1 receptor II, and CD19+CD5+ cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present."

The authors conclude:

"In summary, CD19+CD5+ cells emerge as a novel PE marker and their levels correlate with the disease, as well as with the levels of AT1-AA. Their frequency seems to be regulated by increased hCG levels secreted by the placenta during PE and present in the serum. Our data enormously contribute to the understanding of the complex mechanisms leading to the onset of PE. Of importance, our work first identifies the cellular component related to the production of autoantibodies during pregnancy. The detection and quantification of CD19+CD5+ cells in maternal blood may serve as a noninvasive diagnostic tool, which opens vast new therapeutic opportunities."

Practitioners should not fail to screen for subclinical autoimmunity in patients who wish to become, or already are, pregnant. When autoimmune phenomena are detected the underlying contributing causes can be detected and ameliorated.