A basic study to demonstrate that autoantibodies to factor XII in patients with recurrent pregnancy loss recognize EGF2 domain

2016 ◽  
Vol 118 ◽  
pp. 111 ◽  
Author(s):  
Yoshihiro Sato ◽  
Toshitaka Sugi
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Factor Xii ◽  
Basic Study

The antigenic binding sites of autoantibodies to factor XII in patients with recurrent pregnancy losses

2008 ◽  
Vol 99 (02) ◽  
pp. 316-323 ◽  
Author(s):  
Yoshimi Fujita ◽  
Hidehiko Matsubayashi ◽  
Shun-ichiro Izumi ◽  
Mikio Mikami ◽  
Akifumi Inomo ◽  
...  
Keyword(s):  
Binding Site ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Platelet Glycoprotein ◽  
Factor Xii ◽  
Binding Studies ◽  
Amino Terminal ◽  
Recurrent Pregnancy Losses ◽  
Direct Binding ◽  
Positive Recurrent

SummaryRecently, numerous studies have suggested an association between factor XII (FXII) deficiency and recurrent pregnancy losses, and between autoantibodies to FXII and recurrent pregnancy losses. Autoantibodies to FXII rather than FXII deficiency may be a risk factor for recurrent pregnancy losses. To know the pathogenesis of autoantibodies to FXII, epitope mapping study was done. Seventeen anti-FXII antibody positive recurrent pregnancy loss patients were chosen for this study. We used synthetic peptides in inhibition and direct binding studies to identify the antigenic binding site of autoantibodies to FXII. Among plasmas from 17 recurrent pregnancy loss patients who were positive for autoantibodies to FXII, 13 patients (76.5%) recognized amino acids 1–30, the amino-terminal heavy chain region that is known as factor XII binding site to platelet glycoprotein Ibα.

scholarly journals Factor XII (Hageman) Levels in Women with Recurrent Pregnancy Loss

2014 ◽  
Vol 2014 ◽  
pp. 1-3 ◽  
Author(s):  
A. Seval Ozgu-Erdinc ◽  
Cihan Togrul ◽  
Ayla Aktulay ◽  
Umran Buyukkagnici ◽  
Elif Gul Yapar Eyi ◽  
...  
Keyword(s):  
Observational Study ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Referral Hospital ◽  
Retrospective Observational Study ◽  
Factor Xii ◽  
Normal Range ◽  
Tertiary Referral ◽  
Tertiary Referral Hospital ◽  
Factor Xii Deficiency

Objective. To evaluate factor XII levels in women with recurrent pregnancy loss (RPL) in a tertiary referral hospital.Methods. Women who were referred to our hospital for two consecutive abortions or three abortions in between 2007 and 2013 were included in this retrospective observational study. Women were further grouped according to factor XII levels, as <60% and ≥60%.Results. Mean factor XII level was 109.1 ± 35.7% (range: 9–200). Ninety-three (7.4%) women had factor XII levels < 60%. Mean factor XII level was 44.8 ± 13.1, and levels ranged between 9 and 60 in this group. Only one woman had factor XII level < 10 %. Remaining 1164 (92.6%) women had factor XII levels ≥ 60%. Mean factor XII level was 114.3 ± 31.7, and levels ranged between 60.3 and 200 in this group, while 1015 (72.4%) women had factor XII levels within the normal range (60%–150% [100% = 30 μg/mL]).Conclusion. Decreased activity of F-XII was diagnosed in 7.4% of women with RPL. We concluded factor XII deficiency that might be a rare but significant factor for RPL, and should be evaluated in women who are investigated for recurrent pregnancy loss.

scholarly journals Anti-Factor XII Autoantibodies in Patients with Recurrent Pregnancy Loss Recognize the Second Epidermal Growth Factor–Like Domain

TH Open ◽  
2019 ◽  
Vol 03 (03) ◽  
pp. e263-e272
Author(s):  
Yoshihiro Sato ◽  
Toshitaka Sugi ◽  
Rie Sakai
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Factor Xii ◽  
Heparin Binding ◽  
Binding Studies ◽  
Epidermal Growth ◽  
Adverse Pregnancy ◽  
Egf Family

Background Factor XII (FXII) deficiency and autoantibodies that bind to FXII (anti-FXII) have been described in patients with adverse pregnancy outcomes, including recurrent pregnancy loss. It has been reported that FXII functions not only as a coagulation protein but also as a growth factor. Objectives We studied the association between anti-FXII and the epidermal growth factor (EGF) system in patients with recurrent pregnancy loss. Patients/Methods We used synthetic peptides that span the second EGF-like domain in the heavy chain of FXII (EGF2) in inhibition and direct binding studies to determine if anti-FXII antibodies recognize EGF2. Furthermore, we examined whether anti-FXII antibodies, which recognize EGF2, also recognize recombinant EGF and heparin-binding EGF-like growth factor (HB-EGF). Results Among 100 patients with recurrent pregnancy loss, the plasma of 23 patients (23.0%) recognized the synthetic peptide ASQ41, which covers EGF2. Among the 23 anti-ASQ41-positive patients, plasma samples from 13 patients (56.5%) recognized the 22-residue segment C-terminal half of ASQ41. Among the 23 anti-ASQ41-positive patients, the plasma of 17 patients (73.9%) recognized recombinant human EGF. Affinity-purified anti-FXII antibodies, which recognize ASQ41, also recognized recombinant EGF family proteins such as EGF and HB-EGF. Conclusions The autoantibodies in patients with recurrent pregnancy loss recognized the EGF2 domain in FXII and other proteins of the EGF family. Since proteins in the EGF family play an important role in normal pregnancy, autoantibody-associated disruption of the EGF system may cause pregnancy loss.

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