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

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.

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ASSOCIATED CONDITIONS AND SPECIFIC PREDICTS OF OBSTETRIC ANTIFOSPHOLIPID SYNDROME

Periódico Tchê Química ◽

10.52571/ptq.v16.n31.2019.682_periodico31_pgs_674_680.pdf ◽

2019 ◽

Vol 16 (31) ◽

pp. 674-680

Author(s):

A. N. RODRIGUES ◽

I. C. dos S. ANDRADE ◽

C. M. M. P. de LEON

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Fetal Death ◽

Systemic Disease ◽

Fetal Loss ◽

Recurrent Abortion ◽

Pathogenic Role ◽

Associated Conditions ◽

Obstetric Antiphospholipid Syndrome ◽

In Pregnancy

The antiphospholipid syndrome (APS), or Hughes's disease, an autoimmune systemic disease, is the most common thrombophilias acquired in the young adult. In obstetrics, it is characterized clinically and may be associated with other diseases. The objective of this study was to identify the specific laboratory predictors of high risk for fetal loss, as well as the main associated symptomatologies. This study was performed through data analysis of 1557 pregnant patients diagnosed with classic antiphospholipid syndrome. The condition most associated with patients with obstetric SAF in the present study was the presence of previous abortion, followed by early delivery, thrombosis, fetal death, recurrent abortion and pre-eclampsia. The laboratory predictors associated with obstetric antiphospholipid syndrome were lupus anticoagulant and anticardiolipin IgG / IgM. It is necessary to carry out a study to complement the profile of the patients of this syndrome in pregnancy, because the development of antiphospholipid antibodies appear to be frequent in critically ill patients, but more studies are necessary to clarify their pathogenic role and its implications in clinical practice.

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Thrombogenic Properties of Murine Anti-Cardiolipin Antibodies Induced by β2Glycoprotein 1 and Human Immunoglobulin G Antiphospholipid Antibodies

Circulation ◽

10.1161/01.cir.94.7.1746 ◽

1996 ◽

Vol 94 (7) ◽

pp. 1746-1751 ◽

Cited By ~ 88

Author(s):

Silvia S. Pierangeli ◽

Xiao Wei Liu ◽

G. Anderson ◽

J.H. Barker ◽

E.N. Harris

Keyword(s):

Immunoglobulin G ◽

Antiphospholipid Antibodies ◽

Human Immunoglobulin ◽

Human Immunoglobulin G ◽

Cardiolipin Antibodies

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Organ specific complement proteins inhibition can reduce the risk of antiphospholipid antibodies mediated fetal loss

Medical Hypotheses ◽

10.1016/j.mehy.2012.10.015 ◽

2013 ◽

Vol 80 (1) ◽

pp. 65-66

Author(s):

Annamalai Amarnath ◽

Govindaraju Archunan

Keyword(s):

Antiphospholipid Antibodies ◽

Fetal Loss ◽

Complement Proteins ◽

Organ Specific

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Randomized study of subcutaneous low molecular weight heparin plus aspirin versus intravenous immunoglobulin in the treatment of recurrent fetal loss associated with antiphospholipid antibodies

Arthritis & Rheumatism ◽

10.1002/art.10957 ◽

2003 ◽

Vol 48 (3) ◽

pp. 728-731 ◽

Cited By ~ 149

Author(s):

Giovanni Triolo ◽

Angelo Ferrante ◽

Francesco Ciccia ◽

Antonina Accardo-Palumbo ◽

Antonino Perino ◽

...

Keyword(s):

Molecular Weight ◽

Intravenous Immunoglobulin ◽

Antiphospholipid Antibodies ◽

Low Molecular Weight Heparin ◽

Randomized Study ◽

Fetal Loss ◽

Low Molecular Weight ◽

Recurrent Fetal Loss

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The association of antiphospholipid antibodies with intrauterine fetal death: A case–control study

Thrombosis Research ◽

10.1016/j.thromres.2011.11.029 ◽

2012 ◽

Vol 130 (1) ◽

pp. 32-37 ◽

Cited By ~ 16

Author(s):

Linda Björk Helgadottir ◽

Finn Egil Skjeldestad ◽

Anne Flem Jacobsen ◽

Per Morten Sandset ◽

Eva-Marie Jacobsen

Keyword(s):

Antiphospholipid Antibodies ◽

Fetal Death ◽

Case Control Study ◽

Case Control ◽

Intrauterine Fetal Death ◽

Control Study

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Childhood-Onset Systemic Lupus Erythematosus: Antiphospholipid Antibodies in 37 Patients and Their First-Degree Relatives

PEDIATRICS ◽

10.1542/peds.92.6.849 ◽

1993 ◽

Vol 92 (6) ◽

pp. 849-853

Author(s):

Charles Molta ◽

Olivier Meyer ◽

Christine Dosquet ◽

Marcela Montes de Oca ◽

Marie-Claude Babron ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Clinical Manifestations ◽

Fetal Loss ◽

Childhood Onset ◽

Systemic Lupus ◽

First Degree Relatives ◽

Antiphosphatidylethanolamine Antibodies ◽

Onset Systemic Lupus Erythematosus

Objective. Antiphospholipid antibodies (aPL) are noted with increased frequency in patients with systemic lupus erythematosus (SLE). The main manifestations found to be associated with aPL are arterial and venous thrombotic events, thrombocytopenia, and recurrent pregnancy loss This study is an attempt to define the incidence of aPL in patients with childhood-onset SLE and in their relatives and to correlate their presence with clinical manifestations, and especially, to evaluate the risk of thrombosis in aPL-positive subjects. Methodology. We studied 37 unrelated patients and 107 of their first-degree relatives. VDRL, IgG and IgM anticardiolipin, and IgG antiphosphatidylethanolamine antibodies were studied in all probands during periods of clinical remission and in first-degree relatives at the time of interview. Lupus anticoagulant had only been studied in probands during an SLE flare-up. Results. Thirty-eight percent of probands and 19% of relatives were positive for at least one aPL, with little over-lap between the different aPL studied. -No aPL-negative proband developed thrombosis. Two of the aPL-positive probands had thrombotic events before testing, and a third one showed thrombosis after testing. Only two probands had high levels of IgG aCL and showed thrombosis. The occurrence of aPL positivity in relatives was not always related to its presence in probands. None of the aPL-positive relatives had hadthrombosis, but recurrent fetal loss was noted in one aPL-positive mother with SLE. Although there was a high frequency of SLE, SLE-like disease, auto-immune disorders or positive serological findings for lupus in first-degree relatives, many of these relativew did not test positive for aPL. Conclusion. The high levels of IgG aCL may be considered a risk factor for thrombosis. Findings in relatives suggest a multifactorial origin for autoimmune disease and antibody production.

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IgA Anticardiolipin Antibodies – Relation with other Antiphospholipid Antibodies and Clinical Significance

Thrombosis and Haemostasis ◽

10.1055/s-0037-1614978 ◽

1998 ◽

Vol 79 (02) ◽

pp. 282-285 ◽

Cited By ~ 49

Author(s):

Josep Ordi-Ros ◽

Francesc Monegal-Ferran ◽

Nuria Martinez ◽

Fina Cortes-Hernandez ◽

Miquel Vilardell-Tarres ◽

...

Keyword(s):

Lupus Erythematosus ◽

Antiphospholipid Antibodies ◽

Fetal Loss ◽

Cross Sectional Study ◽

Anticardiolipin Antibodies ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Serum Samples ◽

Cross Sectional ◽

Vein Thrombosis

SummaryObjective: To evaluate the usefulness of IgA antiphospholipid antibodies as markers of thrombosis and/or antiphospholipid antibody syndrome. Patients and Methods: A cross-sectional study design in a tertiary, university-based, autoimmune reference hospital. Seven-hundred ninety-five patients classified into five different groups – autoimmune diseases (255), deep vein thrombosis (153), transitory ischemic attacks (108), obstetric complications (196), infectious diseases (83) and controls (81) – were tested for IgA, IgG and IgM aPL, and lupus anticoagulant. Plasma and serum samples were drawn for detection of aPL using an internationally standardized ELISA method and LA was carried out using coagulometric assays. Results: True IgA aPL were found only in two patients with systemic lupus erythematosus; these patients were also positive to IgG aPL. Conclusion: The incidence of true positivity to IgA anticardiolipin antibodies is extremely low. Their determination was not helpful in diagnosing the antiphospholipid syndrome or in explaining thrombotic events or aPL related manifestations – fetal loss – in the groups studied.

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The Influence of Antiphospholipid Antibodies on the Pregnancy Outcome of Patients With Recurrent Spontaneous Abortion

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602960100700405 ◽

2001 ◽

Vol 7 (4) ◽

pp. 281-285 ◽

Cited By ~ 9

Author(s):

L. Heilmann ◽

G.-F. v. Tempelhoff ◽

S. Kuse

Keyword(s):

Pregnant Women ◽

Intravenous Immunoglobulin ◽

Spontaneous Abortion ◽

Antiphospholipid Antibodies ◽

Lupus Anticoagulant ◽

Standard Therapy ◽

Loss Rate ◽

Fetal Loss ◽

Negative Group ◽

History Of

Several therapeutic regimens have been proposed for women with recurrent spontaneous abortion (RSA) and antiphospholipid antibodies (APA). Conflicting results have been reported about women with history of RSA, positive APA, and failure of standard therapy. To evaluate the use of intravenous immunoglobulin in RSA patients with APA and history of treatment failure, we initiated a study with standard therapy (aspirin and low-molecular- weight heparin) and intravenous immunoglobulin. We used an enzyme-linked immunosorbent assay (ELISA)test to screen IgG and IgM anticardiolipin antibodies, and a diluted Russel viper venom time assay for the lupus anticoagulant activity. Altogether. 66 pregnant women with positive APAs at the first visit could be included. Patients with hereditable thrainbaghilic factors were excluded. After confirmation of the pregnancy, women received a basis immunization of 0.3 g/kg immunoglobulin in a 4-week cycle until the 28th to 32nd week of gestation. All patients received 100 mg/d aspirin and 3,000 anti-Xa U/d certoparin. Among the 66 pregnant women, 17 were persistently autoantibody positive (25.8%), of whom 11 (16.7%) were ACA positive alone, 2 (3%) were lupus anticoagulant positive, and 4 (6.4%) had both antibody types. A total of 49 patients had positive APAs at the initial test, but were negative for ACA and lupus anticoagulant at the second test administered approximately 5 weeks after the start of therapy. We described this group in our following observation as "antibody negative." Sixteen of the 17 autoantibody-positive patients (94.1 %) were delivered of live infants compared with 40 patients (81.6%) in the antibody-negative group (odds ratio [OR]: 1.2; 95% CI: 0.98 to 1.4). The overall miscarriage rate was 12.1% and the fetal loss rate was 15.2%. Four patients (25%) in the antibody-positive group developed symptoms of preeclampsia and fetal growth retardation compared with four patients (9.8%) in the antibody-negative group. In conclusion. we see a reduction of the fetal loss rate in patients with RSA and positive APA (5.8%) compared with APAnegative (18.4%) women with the same therapy (OR: 0.3; 95% CI: 0.04 to 2.3).

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