CD19 ⁺ CD5 ⁺ Cells as Indicators of Preeclampsia

Abstract

Abstract-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 ϩ CD5 ϩ B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures. Here, we aimed to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia and to study their regulation, as well as their possible use as markers for the disease. The frequency of CD19 ϩ CD5 ϩ cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry. 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 Ϸ95% of CD19 ϩ CD5 ϩ cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture. Most importantly, isolated CD19 ϩ CD5 ϩ cells produce autoantibodies against angiotensin type 1 receptor II, and CD19 ϩ CD5 ϩ cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present. Our results identify a B-cell population able to produce pregnancy-pathological autoantibodies as possible markers for preeclampsia, which opens vast diagnostic and therapeutic applications. P reeclampsia (PE) is a devastating human pregnancyassociated disorder characterized by the onset of hypertension, proteinuria, and edema after the 20th week of pregnancy. It represents one of the most frequent medical complications of pregnancy, affecting Ϸ5% to 8% of all pregnant women. 1 Limited progress has been achieved in identifying the causes, being the induction of delivery the only available treatment for the clinical symptoms. 2 Recently, the idea that PE may represent an autoimmune disease has emerged. 3 This is based on the fact that many autoantibodies were identified in PE patients and suspected to account for the symptoms of the disease. [4][5][6] Much attention was focused on autoantibodies against angiotensin type 1 receptor II (AT 1 -AAs), because they have been detected in the serum of PE patients. 7 These autoantibodies are able to bind to and to activate the AT 1 angiotensin receptor, leading to the release of antiangiogenic factors from the placenta, which are reportedly involved in the origin of the disease. [8][9][10] In spite of the efforts put on identifying autoantibodies related to PE, no attention has been so far focused on the cell population responsible for their production. This is a very important piece of information, because it may provide a novel tar...

Choriodecidual leukocytes display a unique gene expression signature in spontaneous labor at term

“…B cells can also be recruited by the chorioamniotic membranes [14] and constitute a portion of the choriodecidual leukocytes [16,57,58]. The role of B cells during pregnancy and its complications have been widely studied by Jensen and collaborators [59][60][61][62][63][64][65][66][67][68]. Taken together, these data provide further evidence that the adaptive limb of immunity is involved in the process of labor.…”

Endocrine Factors Modulating Immune Responses in Pregnancy

“…Even during pregnancy, B1a B cells producing natural antibodies are proposed to have detrimental effects on pregnancy outcome. We recently showed that the number of B1a B cells significantly decrease in the third trimester of normal pregnant women while remain elevated in pre-eclamptic patients (122). As patients suffering from pre-eclampsia have augmented serum hCG levels compared to normal pregnant women, we assumed that hCG may be responsible for the increased B1a B cell number.…”

“…As patients suffering from pre-eclampsia have augmented serum hCG levels compared to normal pregnant women, we assumed that hCG may be responsible for the increased B1a B cell number. This assumption is further underlined by the fact that almost all B1a B cells express the LH/CG receptor and expand in vitro upon hCG stimulation (122). It was however shown that hCG inhibited antibody formation of murine B cells (123, 124).…”

Adaptive Immune Responses During Pregnancy

“…hCG, reported to be elevated in PE patients, was identified as one factor modulating the AT1-AA production by B1aB cells. 111 The application of an antibody that reduces the B-cell population could restore blood pressure and endothelin production in a rat model for PE. 112 …”