Significance of Anti-Phosphatidylethanolamine Antibodies in the Pathogenesis of Recurrent Pregnancy Loss

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ORIGINAL ARTICLE

Significance of Anti-Phosphatidylethanolamine Antibodies in the Pathogenesis of Recurrent Pregnancy Loss Mirei Yonezawa 1 & Yoshimitsu Kuwabara 1 Toshiyuki Takeshita 1

&

Shuichi Ono 1

&

Nozomi Ouchi 1 & Tomoko Ichikawa 1 &

Received: 26 November 2019 / Accepted: 24 April 2020 # Society for Reproductive Investigation 2020

Abstract Anti-phosphatidylethanolamine antibody (aPE), an anti-phospholipid autoantibody (aPL), has been proposed as a factor in recurrent pregnancy loss (RPL). However, conflicting views exist on the pathogenicity of RPL, and aPE has not yet been included in the classification criteria for antiphospholipid syndrome (APS). Here, we aimed to determine the clinical importance of examining aPE. aPE (IgG, IgM) was measured in 1705 patients with a history of RPL and re-examined after a 12-week interval in patients who tested positive. Persistent positive patients were administered low-dose aspirin during the subsequent pregnancy and clinical outcomes depending on the presence, type, and persistence of aPE were evaluated. Among the patients positive for aPE IgG and aPE IgM in the first examination (n = 117; 6.87%, and n = 235; 13.6%, respectively), 31.5% and 37.6% were negative upon re-examination, respectively. Moreover, among the cases with known pregnancy outcome, the miscarriage rate in the cumulative positive aPE group was 32.6% (29/89), which did not differ significantly from that of the aPE negative group (27.7%; 80/209; P = 0.178). Alternatively, the miscarriage rate in the persistently positive group was 40.7% (22/54), which was significantly higher than that in the transient positive group, 20.0% (7/35) (P = 0.041). Particularly, this difference become more significant when focusing on aPE IgM, 46.9% (15/32) in the persistent, compared with 16.7% (4/24) in the transient positive group (P = 0.024). aPE IgM is suggested to serve as a pathogenic aPL together with anti-cardiolipin antibodies and lupus anticoagulants, particularly if these factors persist over an extended period of time. Keywords Anti-phosphatidylethanolamine . Recurrent pregnancy loss . Antiphospholipid syndrome . Persistent positive

Introduction Antiphospholipid syndrome (APS) is characterized by arterial or venous thrombosis and/or an adverse pregnancy outcome in the presence of persistent laboratory evidence of antiphospholipid antibodies (aPLs). In addition to conventional aPLs such as lupus anticoagulant (LA), anti-cardiolipin (aCL) antibody, and anti-β2 glycoprotein I–dependent anticardiolipin (aβ2GPI) antibody, it has been reported that certain other aPLs are associated with thrombosis and adverse pregnancy outcome, including anti-phosphatidylethanolamine (aPE) antibodies.

* Yoshimitsu Kuwabara [email protected] 1

Department of Obstetrics and Gynecology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan

aPE antibodies have been reported to cause thrombotic events and pregnancy complications, including pregnancy loss [1, 2]. Sanmarco and colleagues reported that aPE antibody was ob