scholarly journals Anti-Phosphatidylserine/Prothrombin Antibodies in Healthy Women with Unexplained Recurrent Pregnancy Loss

2021 ◽  
Vol 10 (10) ◽  
pp. 2094
Author(s):  
Daniel E. Pleguezuelo ◽  
Oscar Cabrera-Marante ◽  
Magdalena Abad ◽  
Edgard Alfonso Rodriguez-Frias ◽  
Laura Naranjo ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Fetal Death ◽  
Fetal Loss ◽  
Healthy Women ◽  
Glycoprotein I ◽  
Early Miscarriage ◽  
Beta 2

Recurrent pregnancy loss (RPL) affects up to 6% of couples. Although chromosomal aberrations of the embryos are considered the leading cause, 50% of cases remain unexplained. Antiphospholipid Syndrome is a known cause in a few cases. Antiphospholipid antibodies (aPL) anticardiolipin, anti-Beta-2-Glycoprotein-I and Lupus Anticoagulant (criteria aPL) are recommended studies in RPL workup. We tested healthy women with unexplained RPL for criteria aPL and anti-Phosphatidylserine/Prothrombin antibodies (aPS/PT). Patients were classified into three groups according to the number and pregnancy week of RPL: Extra-Criteria (EC), with 2 miscarriages, Early Miscarriage (EM), with ≥3 before pregnancy at week 10 and Fetal Loss (FL), with ≥1 fetal death from pregnancy at week 10. Circulating criteria aPL were absent in 98.1% of EM, 90.9% of FL and 96.6% of EC groups. In contrast, aPS/PT were positive in 15.4% of EM, 15.1% of FL, 16.6% of EC patients and 2.9% in controls. aPS/PT posed a risk for RPL, with an odds ratio of 5.96 (95% confidence interval (CI): 1.85–19.13. p = 0.002) for EM, 7.28 (95% CI: 2.07–25.56. p = 0.002) for FL and 6.56. (95% CI: 1.77–24.29. p = 0.004) for EC. A successful live birth was achieved in all pregnant patients positive for aPS/PT who received treatment with heparin, aspirin and/or hydroxychloroquine.

scholarly journals The role of anti-phospholipid antibodies in autoimmune reproductive failure

Reproduction ◽  
2016 ◽  
Vol 151 (5) ◽  
pp. R79-R90 ◽  
Author(s):  
Priyadarshini Pantham ◽  
Vikki M Abrahams ◽  
Lawrence W Chamley
Keyword(s):  
Animal Models ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Plasma Binding ◽  
Present Evidence ◽  
Glycoprotein I ◽  
Cardiolipin Antibodies ◽  
Beta 2 ◽  
In Pregnancy

AbstractAnti-phospholipid antibodies (aPL) are autoantibodies that are associated with thrombosis and a range of pregnancy complications including recurrent pregnancy loss and pre-eclampsia. The three clinically relevant, well-characterized aPL are anti-cardiolipin antibodies, lupus anticoagulant and anti-beta-2-glycoprotein I (β2GPI) antibodies. aPL do not bind directly to phospholipids but instead bind to a plasma-binding ‘cofactor’. The most extensively studied cofactor is β2GPI, whose role in pregnancy is not fully elucidated. Although the pathogenicity of aPL in recurrent pregnancy loss is well established in humans and animal models, the association of aPL with infertility does not appear to be causative. aPL may exert their detrimental effects during pregnancy by directly binding trophoblast cells of the placenta, altering trophoblast signalling, proliferation, invasion and secretion of hormones and cytokines, and by increasing apoptosis. Heparin is commonly used to treat pregnant women with aPL; however, as thrombotic events do not occur in the placentae of all women with aPL, it may exert a protective effect by preventing the binding of aPL to β2GPI or by acting through non-thrombotic pathways. The aim of this review is to present evidence summarizing the current understanding of this field.

Immunoglobulin G fractions from patients with antiphospholipid antibodies cause fetal death in BALB/c mice: A model for autoimmune fetal loss

1990 ◽  
Vol 163 (1) ◽  
pp. 210-216 ◽  
Author(s):  
D. Ware Branch ◽  
Donald J. Dudley ◽  
Murray D. Mitchell ◽  
Kathryn A. Creighton ◽  
Thomas M. Abbott ◽  
...  
Keyword(s):  
Immunoglobulin G ◽  
Antiphospholipid Antibodies ◽  
Fetal Death ◽  
Fetal Loss

scholarly journals Molecular Mechanisms of “Antiphospholipid Antibodies” and Their Paradoxical Role in the Pathogenesis of “Seronegative APS”

2020 ◽  
Vol 21 (21) ◽  
pp. 8411
Author(s):  
Roberta Misasi ◽  
Agostina Longo ◽  
Serena Recalchi ◽  
Daniela Caissutti ◽  
Gloria Riitano ◽  
...  
Keyword(s):  
Antiphospholipid Antibodies ◽  
Molecular Mechanisms ◽  
Strong Association ◽  
Fetal Loss ◽  
Signal Transduction Pathway ◽  
Therapeutic Strategies ◽  
Transduction Pathway ◽  
Laboratory Methods ◽  
Pregnancy Morbidity ◽  
Glycoprotein I

Antiphospholipid Syndrome (APS) is an autoimmune disease characterized by arterial and/or venous thrombosis and/or pregnancy morbidity, associated with circulating antiphospholipid antibodies (aPL). In some cases, patients with a clinical profile indicative of APS (thrombosis, recurrent miscarriages or fetal loss), who are persistently negative for conventional laboratory diagnostic criteria, are classified as “seronegative” APS patients (SN-APS). Several findings suggest that aPL, which target phospholipids and/or phospholipid binding proteins, mainly β-glycoprotein I (β-GPI), may contribute to thrombotic diathesis by interfering with hemostasis. Despite the strong association between aPL and thrombosis, the exact pathogenic mechanisms underlying thrombotic events and pregnancy morbidity in APS have not yet been fully elucidated and multiple mechanisms may be involved. Furthermore, in many SN-APS patients, it is possible to demonstrate the presence of unconventional aPL (“non-criteria” aPL) or to detect aPL with alternative laboratory methods. These findings allowed the scientists to study the pathogenic mechanism of SN-APS. This review is focused on the evidence showing that these antibodies may play a functional role in the signal transduction pathway(s) leading to thrombosis and pregnancy morbidity in SN-APS. A better comprehension of the molecular mechanisms triggered by aPL may drive development of potential therapeutic strategies in APS patients.

scholarly journals Association between Platelet-Specific Collagen Receptor Glycoprotein 6 Gene Variants, Selected Biomarkers, and Recurrent Pregnancy Loss in Korean Women

Genes ◽  
2020 ◽  
Vol 11 (8) ◽  
pp. 862
Author(s):  
Hui Jeong An ◽  
Eun Hee Ahn ◽  
Jung Oh Kim ◽  
Chang Soo Ryu ◽  
Han Sung Park ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Confidence Interval ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Adjusted Odds Ratio ◽  
Recurrent Pregnancy Loss ◽  
Korean Women ◽  
Chain Reaction ◽  
Genotype Frequencies ◽  
Polymerase Chain

This paper investigates whether glycoprotein 6 (GP6) gene polymorphisms are a risk factor for recurrent pregnancy loss (RPL) in Korean women. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism and real-time polymerase chain reaction amplification. We identified five polymorphisms in the GP6 gene: rs1654410 T>C, rs1671153 T>G, rs1654419 G>A, rs12610286 A>G, and rs1654431 G>A. GP6 rs1654410 CC was associated with decreased RPL risk (adjusted odds ratio = 0.292, 95% confidence interval = 0.105–0.815, p = 0.019), and recessive genotypes were also significantly associated with decreased RPL risk (adjusted odds ratio = 0.348, 95% confidence interval = 0.128−0.944, p = 0.038). GP6 rs1654419 GA was associated with decreased RPL risk (adjusted odds ratio = 0.607, 95% confidence interval = 0.375-0.982, p = 0.042), and dominant genotypes were significantly associated with decreased RPL risk (adjusted odds ratio = 0.563, 95% confidence interval = 0.358−0.885, p = 0.013). Altogether, the genotype frequencies of GP6 rs1654410 T>C and GP6 rs1654419 G>A were significantly different between RPL patients and control participants. Therefore, although GP6 polymorphisms may be useful as biomarkers of RPL, additional studies with heterogeneous cohorts are required to better understand the influence of GP6 and assess its performance as a biomarker.

scholarly journals Association Study between the Polymorphisms of Matrix Metalloproteinase (MMP) Genes and Idiopathic Recurrent Pregnancy Loss

Genes ◽  
2019 ◽  
Vol 10 (5) ◽  
pp. 347 ◽  
Author(s):  
Han Sung Park ◽  
Ki Han Ko ◽  
Jung Oh Kim ◽  
Hui Jeong An ◽  
Young Ran Kim ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Odds Ratio ◽  
Pregnancy Loss ◽  
Adjusted Odds Ratio ◽  
Recurrent Pregnancy Loss ◽  
Proteolytic Enzymes ◽  
Nucleotide Polymorphisms ◽  
Genotype Combination ◽  
History Of ◽  
Consecutive Pregnancy

Recurrent pregnancy loss (RPL) refers to two or more consecutive pregnancy losses. It is estimated that fewer than 5% of women experience RPL. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that play important roles in providing a safe and conducive environment for the stable development of the fetus. In this case-control study, we evaluated the associations between RPL and single nucleotide polymorphisms (SNPs) in MMP-8 and MMP-27. We recruited 375 Korean women with a history of RPL and 240 ethnically-matched healthy parous controls, and we performed genotyping for the MMP-8 rs2509013 C>T, MMP-8 rs11225395 G>A, and MMP-27 rs3809017 T>C polymorphisms. All SNPs were genotyped via the polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) assay. In the genotype frequency analyses, the TT genotype of the MMP-8 rs2509013 C>T (age-adjusted odds ratio, 0.415; 95% confidence interval, 0.257–0.671; P = 0.0003) and TC genotype of MMP-27 rs3809017 T>C (age-adjusted odds ratio, 0.681; 95% confidence interval, 0.483–0.961; P = 0.029) were associated with decreased RPL susceptibility. Moreover, these trends were maintained in the haplotype and genotype combination analyses. Interestingly, amongst the RPL patients, higher levels of homocysteine (P = 0.042) and uric acid (P = 0.046) were associated with MMP-27 rs3809017 T>C. In conclusion, the two polymorphisms of MMP-8 and MMP-27 were significantly associated with RPL risk, both individually and in combination. Therefore, these two polymorphisms are potential biomarkers for RPL susceptibility.

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