Autoantibodies to Factor XII and Kininogen‐Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation

Satō, Yoshihiro; Sugi, Toshitaka; Sakai, Rie

doi:10.1111/aji.12402

Cited by 3 publications

(5 citation statements)

References 45 publications

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“…13 14 This suggests that anti-FXII species that recognize IPP30 in patients with recurrent pregnancy loss may inhibit FXII binding to platelets, which leads to thrombosis and pregnancy loss. Results from our previous study 15 supported this hypothesis and demonstrated that exogenously added polyclonal antibodies against IPP30 markedly increased γ-thrombin-induced platelet aggregation in vitro. Furthermore, it was reported that, in a murine model, anti-FXII infusion (or infusion of anti-IPP30 antibodies) induced placental thrombosis and hemorrhage as well as increased placental apoptosis.…”

Section: Introductionsupporting

confidence: 60%

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

Satō¹,

Sugi²,

Sakai³

2019

TH Open

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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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Section: Introductionsupporting

confidence: 60%

“…17 18 19 We screened patients for aPE because our previous study suggested that 37.5% of patients with recurrent pregnancy loss who were positive for anti-FXII antibodies were also positive for aPE and that these autoantibodies may have similar structures and functions. 15…”

Section: Methodsmentioning

confidence: 99%

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

Satō¹,

Sugi²,

Sakai³

2019

TH Open

Self Cite

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“…Since half of the patients with an early miscarriage had antibodies to PE and An V, it was suggested that autoimmune mechanisms could be involved in the development of this pregnancy complication. Previously, it has been shown that the antibodies to PE and An V are possible risk factors for a recurrent miscarriage [ 41 , 42 ]. These results are consistent with a meta-analysis that showed a higher incidence of aPL in women with failed IVF/ICSI cycles than women with successful cycles [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

The Effect of COVID-19 Severity, Associated Serum Autoantibodies and Time Interval after the Disease on the Outcomes of Fresh Oocyte ART Cycles in Non-Vaccinated Patients

Dolgushina,

Menzhinskaya,

Ermakova

et al. 2023

JCM

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It is assumed that SARS-CoV-2- and COVID-19-associated autoimmune processes may affect the outcomes in assisted reproductive technology (ART) cycles. This observational prospective study included 240 infertile patients: 105 patients had no history of COVID-19 (group 1) and 135 patients had experienced COVID-19 (group 2) in a mild (n = 85) or moderate (n = 50) form less than 12 months prior to oocyte retrieval. Using ELISAs, the profiles of their serum autoantibodies were determined, including antiphospholipid antibodies and antibodies to nuclear and thyroid antigens. The parameters of oogenesis and embryogenesis, as well as the pregnancy and childbirth rates, did not differ between groups 1 and 2, and also between the subgroups with different severities of COVID-19. However, when oocyte retrieval was performed less than 180 days after COVID-19, a higher proportion of poor-quality blastocysts was obtained (p = 0.006). A high risk of early miscarriage was found in the patients with moderate COVID-19. In group 2, IgG antibodies to annexin V, phosphatidylethanolamine (PE), and TSHr were detected more often than in group 1 (p = 0.035; p = 0.028; and p = 0.033, respectively), and a weak inverse correlation was revealed between anti-PE IgG and the number of oocytes and zygotes obtained. The results of the study suggest a possible adverse effect of COVID-19 and its associated autoantibodies on the outcomes of fresh oocyte ART cycles and early pregnancy, which depends on the severity of COVID-19 and the time interval after the disease.

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“…reported that female mice homozygous for total factor XII deficiency had normal deliveries with normal litter sizes, suggesting that congenital factor XII deficiency is not associated with pregnancy loss. Some studies reported that antibodies against factor XII have a strong significant association with RPL . Therefore, autoantibodies against factor XII rather than factor XII deficiency may be a risk factor for thromboembolism and RPL.…”

Section: Discussionmentioning

confidence: 99%

“…Some studies reported that antibodies against factor XII have a strong significant association with RPL. 24,25 Therefore, autoantibodies against factor XII rather than factor XII deficiency may be a risk factor for thromboembolism and RPL.…”

Section: Discussionmentioning

confidence: 99%

Risk Factors and Outcomes of Recurrent Pregnancy Loss in Japan

Morita

Ono

Takeshita

et al. 2019

J of Obstet and Gynaecol

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Aim To clarify the risk factors and pregnancy outcomes for each risk factor of recurrent pregnancy loss (RPL) in Japan. Methods Using a prospective RPL database collected from 16 facilities in Japan, the prevalence of risk factors for RPL, their treatments and pregnancy outcomes were examined. Results Of 6663 patients registered in our database, 5708 patients had RPL. All examinations for risk factors were performed for 1340 patients (23.5%). The prevalences of positive antiphospholipid antibodies (aPL), malformation of the uterus, thyroid dysfunction, parental karyotype abnormality, factor XII deficiency, protein S deficiency and unknown risk factors were 8.7%, 7.9%, 9.5%, 3.7%, 7.6%, 4.3% and 65.1%, respectively. Although factor XII deficiency and protein S deficiency are not recognized as risk factors for RPL in general, low‐dose aspirin (LDA) or unfractionated heparin + LDA therapy improved live birth rates. In transiently aPL‐positive patients, the live birth rate with LDA therapy was similar to that with heparin + LDA. For unknown risk factors of RPL, the live birth rate in normal fetal karyotype in the none treatment group was similar to that in all other treatments group (81.3% vs 86.0%). Of 5708 RPL patients, pregnancy outcomes were known for 2261 patients and 1697 patients (75.1%) had at least one live birth. Conclusion The risk factors and pregnancy outcomes for each risk factor of RPL are useful for clinicians and patients. Factor XII deficiency and protein S deficiency may be risk factors of RPL.

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Autoantibodies to Factor XII and Kininogen‐Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation

Cited by 3 publications

References 45 publications

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

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

The Effect of COVID-19 Severity, Associated Serum Autoantibodies and Time Interval after the Disease on the Outcomes of Fresh Oocyte ART Cycles in Non-Vaccinated Patients

Risk Factors and Outcomes of Recurrent Pregnancy Loss in Japan

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