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1.
Sci Rep ; 14(1): 20529, 2024 09 04.
Article in English | MEDLINE | ID: mdl-39227704

ABSTRACT

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis and obstetric morbidity, with accurate laboratory examination of antiphospholipid antibodies (aPLs) being crucial for diagnosis. This study focused on anti-ß2 glycoprotein I (aß2GPI) antibodies and aimed to establish the first population-based cutoff values for aß2GPI IgA/IgM/IgG antibodies in non-pregnant women of reproductive age in Southwest China. The study cohort comprised 181 healthy women of reproductive age for study. Blood samples were collected on an early morning fast. Anti-ß2GPI antibodies including IgA, IgM and IgG were measured in serum using the HOB® BioCLIA kit. According to the Clinical and Laboratory Standards Institute (CLSI) guidelines, the study used non-parametric percentile methods to calculate the 95th, 97.5th, and 99th percentiles cutoff values for aß2GPI IgA/IgM/IgG antibodies, along with corresponding 90% confidence intervals (CI), while excluding outliers. A total of 168 independent samples were collected for verification, including 85 samples from healthy subjects and 83 samples from APS patients, in order to evaluate the analytical performance of the obtained cutoff values. The 99th percentile cutoff values were 3.36 RU/mL for aß2GPI IgA, 27.54 RU/mL for aß2GPI IgM and 1.81 RU/mL for aß2GPI IgG, which indicated that the levels of aß2GPI IgM antibodies were generally higher compared to those of IgA and IgG antibodies. Our established reference range was confirmed to be successful in validating the detected values of aß2GPI antibodies in all healthy controls. With the 99th percentile cutoff value, the sensitivity was 14.46% for aß2GPI IgA, 22.89% for aß2GPI IgG, and 9.64% for aß2GPI IgM in APS patients. This study established population-based cutoff values that are applicable to the local population for the accurate laboratory examination of aß2GPI antibodies in non-pregnant women of reproductive age. The study also recommends paying more attention to IgM positivity in women of reproductive age.


Subject(s)
Antiphospholipid Syndrome , Immunoglobulin G , Immunoglobulin M , beta 2-Glycoprotein I , Humans , Female , beta 2-Glycoprotein I/immunology , Adult , China , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/diagnosis , Immunoglobulin M/blood , Immunoglobulin G/blood , Immunoglobulin G/immunology , Immunoglobulin A/blood , Middle Aged , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Young Adult , Reference Values , Autoantibodies/blood , Autoantibodies/immunology , Adolescent
2.
Autoimmunity ; 57(1): 2391350, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39155523

ABSTRACT

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by recurrent arteriovenous thrombosis and pathological pregnancy, accompanied by persistent antiphospholipid antibodies, (aPL). The incidence of APS is increasing year by year, clinicians lack of understanding of this type of disease, easy to misdiagnose and miss the diagnosis. Therefore, it is extremely important to establish a suitable animal model to reduce the process of disease development as much as possible and improve clinicians' understanding and understanding. This review will summarize the animal models of APS from the aspects of modeling methods, modeling mechanism, evaluation indicators and advantages and disadvantages of methods, providing a reference for finding an animal model highly similar to human APS, helping researchers to further clarify the pathogenesis of APS and find potential therapeutic targets, so as to achieve early diagnosis, early intervention, and ultimately improve the prognosis of patients.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Disease Models, Animal , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/diagnosis , Animals , Humans , Antibodies, Antiphospholipid/immunology , Mice , Pregnancy
3.
J Reprod Immunol ; 165: 104316, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39173333

ABSTRACT

INTRODUCTION: The objective of this study was to investigate both antiphospholipid antibodies (aPLs) and non-criteria aPLs (NC-aPLs) in relation with pregnancy outcomes. METHODS: We retrospectively analyzed 1574 pregnant women with experienced at least one miscarriage who were tested for aPLs and NC-aPLs, and compared their clinical characteristics, immune biomarkers, and pregnancy outcomes. The χ2 test or Fisher's exact test compared pregnancy outcomes among patients negative for all aPLs, positive for NC­aPLs subtypes, and positive for criteria aPLs subtypes. RESULTS: Multivariate logistic regression analysis indicated that positive aPLs (OR = 2.216, 95 % CI 1.381-3.558), and positive NC-aPLs (OR = 1.619, 95 % CI 1.245-2.106) are linked to adverse outcomes. For fetal loss, positive aPLs (OR = 2.354, 95 % CI 1.448-3.829), NC-aPLs (OR = 1.443, 95 % CI 1.076-1.936) were significant. Premature delivery was associated with positive NC-aPLs (OR = 2.102, 95 % CI 1.452-3.043). In the NC-aPLs positive group, the rate of adverse outcomes was higher in the multiple-positive subgroup (77.8 %) compared to the double-positive (52.3 %) and single-positive (37.0 %) subgroups. The rates of fetal loss and premature delivery were also higher in the multiple-positive NC-aPLs subgroup compared to the single-positive subgroup (48.1 % vs. 22.6 % for fetal loss and 57.1 % vs. 16.5 % for premature delivery). DISCUSSION: Our findings suggest that both aPLs and NC-aPLs are associated with an increased incidence of adverse pregnancy outcomes, and patients presenting with multiple NC-aPLs positivity were found to have a higher incidence of adverse outcomes compared to their single-positive counterparts.


Subject(s)
Abortion, Spontaneous , Antibodies, Antiphospholipid , Pregnancy Outcome , Humans , Pregnancy , Female , Retrospective Studies , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Adult , Abortion, Spontaneous/immunology , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/blood , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/diagnosis , Biomarkers/blood , Premature Birth/immunology , Premature Birth/epidemiology
4.
Am J Reprod Immunol ; 92(2): e13914, 2024 Aug.
Article in English | MEDLINE | ID: mdl-39136233

ABSTRACT

INTRODUCTION: We aimed to investigate the association between perinatal outcomes and placental pathological features in pregnant women with ACTD, including systemic lupus erythematosus (SLE), antiphospholipid antibody syndrome (APS), and undifferentiated connective tissue disease (UCTD). MATERIALS AND METHODS: Placental tissue from SLE (n = 44), APS (n = 45), and UCTD (n = 45) were included, and contemporaneous deliveries of placenta were served as a control group (n = 46) between September 2015 and March 2021. The placental histopathology was evaluated using the Manual of Human Placental Pathology and classified according to the Amsterdam consensus framework. RESULTS: SLE pregnant women have a higher rate of cesarean section (61.40%), premature birth (24.56%), and SGA (26.32%) when compared to control group (p = 0.008, p = 0.005, and p = 0.000, respectively). The rate of vascular malperfusion, inflammatory-immune lesions, and other placental lesions in the SLE group was 47.73%, 56.82%, and 63.64%, which were higher than the control group (p = 0.000, p = 0.000, and p = 0.006, respectively). In the meantime, the incidence of inflammatory-immune lesions in the APS group (42.22%, p = 0.004) and vascular malperfusion in the UCTD group (37.78%, p = 0.007) were increased when compared to the control group. CONCLUSIONS: SLE appeared to confer increased risk for a wide range of adverse perinatal outcomes. We determined elevated placental histopathology risk for most women with ACTD, including vascular maldevelopment, vascular malperfusion, and inflammatory-immune lesions.


Subject(s)
Lupus Erythematosus, Systemic , Placenta , Pregnancy Complications , Pregnancy Outcome , Humans , Female , Pregnancy , Placenta/pathology , Placenta/immunology , Adult , Pregnancy Complications/immunology , Lupus Erythematosus, Systemic/pathology , Antiphospholipid Syndrome/pathology , Antiphospholipid Syndrome/immunology , Infant, Newborn , Connective Tissue Diseases/pathology , Connective Tissue Diseases/immunology , Premature Birth , Undifferentiated Connective Tissue Diseases/immunology , Undifferentiated Connective Tissue Diseases/pathology , Cesarean Section
5.
Med Clin (Barc) ; 163 Suppl 1: S4-S9, 2024 08.
Article in English, Spanish | MEDLINE | ID: mdl-39174152

ABSTRACT

Antiphospholipid antibodies (aPL) are a family of autoantibodies targeting phospholipid-binding proteins and are associated with several clinical settings, and most notably define the antiphospholipid syndrome (APS). These antibodies can be identified using a variety of laboratory tests, which include both solid-phase immunological assays and functional clotting assays that detect lupus anticoagulants (LA). aPLs are linked to a range of adverse medical conditions, such as thrombosis and complications affecting the placenta and fetus, potentially leading to morbidity and mortality. The specific aPL identified, along with the pattern of reactivity, correlates with the severity of these conditions. Therefore, laboratory testing for aPL is crucial for evaluating the risk of complications and for fulfilling certain classification criteria for APS, which are also applied as diagnostic markers in medical practice. This review provides an overview of the available laboratory tests currently for measuring aPL and discusses their clinical implications.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Antibodies, Antiphospholipid/blood , Pregnancy , Female , Lupus Coagulation Inhibitor/blood , Biomarkers/blood
6.
Autoimmun Rev ; 23(6): 103585, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39094811

ABSTRACT

OBJECTIVES: This review aims to identify biological markers associated with the risk of recurrence of thrombotic and/or obstetric events in patients with antiphospholipid syndrome (APS). METHODS: A comprehensive review of literature was conducted to evaluate established and potential novel biological markers associated with thrombosis in APS. To this end, a PubMed literature search was conducted for the last twenty years using the following keywords or their combinations: thrombotic risk, recurrence of thrombosis, risk stratification, severity, predictive value. RESULTS: Previous studies showed that multiple aPL positivity correlates with an increased risk of thrombosis in APS. Moreover, the analysis of N-glycosylation of antiphospholipid antibodies (aPL) revealed that low levels of IgG sialylation, fucosylation or galactosylation increases the pro-inflammatory activity of aPL, predisposing to thrombosis. In addition, quantification of neutrophil extracellular traps (NETs) and antibodies directed against NETs (anti-NETs) in serum demonstrates promising prognostic utility in assessing APS severity. Oxidative stress plays a role in the pathogenicity of APS and paraoxonase 1 (PON1) activity emerges as a promising biomarker of thrombotic risk in APS. Furthermore, identification of novel antigenic targets involved in the pathophysiology of APS, such as lysobisphosphatidic acid (LBPA), had led to the discovery of unconventional aPL, antibodies directed against the LBPA (aLBPA), whose clinical value could make it possible to identify APS patients at high risk of thrombotic recurrence. CONCLUSION: The immunological profile of aPL, N-glycosylation of aPL, quantification of NETs and anti-NETs, analysis of biomarkers of oxidative stress and the discovery of aLBPA offer potential prognostic tools for risk stratification in APS patients.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Biomarkers , Recurrence , Thrombosis , Humans , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/blood , Biomarkers/blood , Thrombosis/etiology , Thrombosis/immunology , Thrombosis/blood , Antibodies, Antiphospholipid/immunology , Antibodies, Antiphospholipid/blood , Prognosis , Risk Factors
8.
Sci Rep ; 14(1): 15975, 2024 07 10.
Article in English | MEDLINE | ID: mdl-38987260

ABSTRACT

Psoriasis is a chronic inflammatory disease that sometimes necessitates therapeutic intervention with biologics. Autoantibody production during treatment with tumor necrosis factor (TNF) inhibitors is a recognized phenomenon, however, the production of autoantibodies associated with antiphospholipid syndrome (APS) has not been comprehensively evaluated in patients with psoriasis. This study was conducted to assess the prevalence of APS-associated autoantibodies in patients with psoriasis treated with different biologics and to investigate the potential associations between autoantibody production and clinical or serological parameters. Patients with psoriasis undergoing biologics treatments were enrolled in this study, and were categorized based on the type of biologics administered, TNF, interleukin (IL)-17, or IL-23 inhibitors. Clinical and serological data were collected and analyzed in conjunction with data on APS autoantibodies. TNF inhibitors were associated with a higher frequency of APS autoantibodies compared to IL-17 and IL-23 inhibitors. Notably, the presence of APS autoantibodies correlated with concurrent arthritis and higher disease severity at treatment initiation in patients treated with TNF inhibitors. Elevated Psoriasis Area and Severity Index scores and anti-nuclear antibody titers higher than × 320 were predictors of APS autoantibody production. Despite the higher autoantibody rates, clinical symptoms of APS were absent in these patients. This study provides the first comprehensive evidence of an increased frequency of APS autoantibodies associated with TNF inhibitor treatment in patients with psoriasis. The observed association between APS autoantibody positivity and TNF inhibitor treatment or clinical parameters suggests a potential immunomodulatory interplay between autoimmunity and inflammation in the pathogenesis of psoriasis.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Biological Products , Psoriasis , Humans , Psoriasis/drug therapy , Psoriasis/immunology , Female , Male , Middle Aged , Biological Products/therapeutic use , Biological Products/adverse effects , Adult , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/drug therapy , Interleukin-17/antagonists & inhibitors , Interleukin-17/immunology , Interleukin-23/immunology , Interleukin-23/antagonists & inhibitors , Tumor Necrosis Factor-alpha/antagonists & inhibitors , Tumor Necrosis Factor-alpha/immunology , Prevalence , Aged , Autoantibodies/blood , Autoantibodies/immunology , Severity of Illness Index , Tumor Necrosis Factor Inhibitors/therapeutic use , Tumor Necrosis Factor Inhibitors/adverse effects
9.
Clin Chim Acta ; 562: 119849, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38977171

ABSTRACT

BACKGROUND: Diagnosing Antiphospholipid Syndrome (APS) relies heavily on laboratory findings, particularly the detection of specific antibodies like lupus anticoagulant (LA), IgG and/or IgM anti-cardiolipin (aCL), and IgG and/or IgM anti-ß2 glycoprotein 1 (aB2GP1). Although ELISA is widely used in the US for this purpose, standardization between different assay methodologies remains challenging, leading to significant variability across laboratories. Particle-based multi-analyte technology (PMAT) offers a streamlined one-step detection for all six antiphospholipid (aPL) autoantibodies, covering aCL and aB2GP1 of IgA, IgG, and IgM isotypes. METHODS: In this study involving 224 subjects, including 34 clinically diagnosed with APS, alongside 160 non-APS patients and 30 healthy donors, PMAT's performance was evaluated against commercial ELISA in detecting aPL antibodies. RESULTS: At the manufacturer's suggested cutoff, PMAT exhibited sensitivity comparable to ELISA, albeit with a low to moderate decrease in specificity for certain antibodies. With anti-CL IgM alone, PMAT displayed a 17.7% decrease in sensitivity, accompanied by a corresponding 31.1% increase in specificity compared to ELISA. However, applying a stricter cutoff (88-90% specificity), IgA and IgM antibodies yielded 5.9-17.6% higher sensitivities with PMAT, and IgG antibodies displayed similar sensitivity. CONCLUSIONS: In this study cohort, PMAT demonstrated higher or comparable sensitivity to that of commercial ELISA for all six aPL antibodies at a specificity cutoff near 90%. Notably, PMAT demonstrated superior sensitivity and specificity overall in detecting IgA aCL and aB2GP1 antibodies. This study highlights the potential of automated PMAT for detecting aPL antibodies in APS evaluation.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Enzyme-Linked Immunosorbent Assay , Humans , Enzyme-Linked Immunosorbent Assay/methods , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antibodies, Antiphospholipid/analysis , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Female , Male , Adult
10.
Placenta ; 154: 122-128, 2024 09 02.
Article in English | MEDLINE | ID: mdl-38959700

ABSTRACT

INTRODUCTION: Antiphospholipid syndrome (APS) is a cause of pregnancy morbidity. We aim to determine the frequency of criteria and non-criteria anti-phospholipid (aPL) autoantibodies in patients admitted for unexplained fetal death (UFD), pre-eclampsia (PE) and/or fetal growth restriction (FGR). METHODS: All consecutive patients with UFD, PE and/or FGR followed in the department of Obstetrics, Bichat Hospital, University of Paris, Paris, between January 2019 and December 2021 were screened. Patients with available serum stored from the index pregnancy were included. Patients with previously known APS or twin pregnancy were excluded. Testing for aPL autoantibodies included anti-cardiolipin (aCL), anti-ß2GPI (aß2GPI), anti-phosphatidylethanolamine (aPE), anti-phosphatidylserine/prothrombin (aPS/PT) IgG/IgM and anti-annexin V IgG. When available, placenta specimens were analyzed by a pathologist blinded to the aPL status. All clinical characteristics, pregnancy features, and comorbidities were extracted from electronic medical records. RESULTS: Overall 167 (32 (28.8-35.7) years) patients with UFD (n = 28; 16.8 %), PE (n = 60; 35.9 %) and/or FGR (n = 105; 62.9 %) were screened for aPL autoantibodies. Moderate titers of aPL autoantibodies were detected in 33 (n = 33/167, 19.8 %) patients. aPL autoantibodies were non-criteria aPE IgG/IgM in most cases (n = 28/33, 84.8 %). aPS/PT IgG/IgM were found in 11 (n = 11/33, 33.3 %) cases and aCL or aß2GP1 IgG/IgM in 4 (n = 4/33, 12.1 %). Multivariable logistic regression showed that aPL autoantibodies were mostly associated with UFD (OR 4.37 [1.72-11.20], p = 0.002), PE ≤ 34th week of gestation (3.22 [0.86-11.90], p = 0.070) and chronic deciduitis (8.03 [0.89-67.2], p = 0.060) DISCUSSION: The frequency of aPL autoantibodies, mostly aPE, is high in patients with late pregnancy morbidity and may qualify obstetrical APS.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Humans , Female , Pregnancy , Adult , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Cross-Sectional Studies , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/blood , Fetal Growth Retardation/immunology , Fetal Growth Retardation/blood , Fetal Death , Pre-Eclampsia/immunology , Pre-Eclampsia/blood , Pregnancy Complications/immunology , Pregnancy Complications/blood
11.
J Reprod Immunol ; 165: 104297, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39029322

ABSTRACT

Recurrent pregnancy loss (RPL) affects 1-2 % of all couples trying to conceive and is a challenging heterogeneous condition. This study aimed to evaluate the prevalence and impact of various risk factors in patients suffering from RPL. We performed a prospective cohort study including patients at the tertiary RPL Unit in the Capital Region of Denmark between 1st January 2000 and 1st January 2023. The main outcome of the study was the first pregnancy after referral and whether the pregnancy was ongoing at least to the 22nd gestational week. A total of 2555 patients were included in the study, out of whom 1892 patients achieved a pregnancy after referral to the RPL Unit. This resulted in 1103 live births (58.3 %) and 718 pregnancy losses (37.9 %). Maternal age, BMI, smoking status and the number of prior pregnancy losses were negatively correlated with the likelihood of achieving pregnancy. Furthermore, maternal age, prior pregnancy losses, antiphospholipid syndrome (APS) and uterine malformations were associated with reduced birth rates. Patients with secondary RPL had a higher birth rate compared to those with primary RPL, and patients with APS treated with low-molecular-weight heparin (LMWH) demonstrated a significantly increased birth rate compared to untreated APS patients. These findings suggest that certain risk factors significantly impact the likelihood of achieving pregnancy and live birth following RPL, which can be used in patient guidance.


Subject(s)
Abortion, Habitual , Live Birth , Humans , Female , Pregnancy , Abortion, Habitual/epidemiology , Abortion, Habitual/immunology , Adult , Prospective Studies , Risk Factors , Live Birth/epidemiology , Antiphospholipid Syndrome/epidemiology , Antiphospholipid Syndrome/immunology , Maternal Age , Denmark/epidemiology , Pregnancy Outcome/epidemiology , Heparin, Low-Molecular-Weight/therapeutic use , Birth Rate , Cohort Studies
12.
Int J Rheum Dis ; 27(7): e15253, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38967004

ABSTRACT

Antiphospholipid Syndrome (APS), characterized by hypercoagulability and pregnancy morbidity, poses a significant clinical challenge when involving organ systems, such as the endocrine system. APS can directly and indirectly influence the anterior and posterior lobes of the pituitary gland. The thyroid gland exhibits involvement, especially in patients with positive anticardiolipin antibodies, yet the clinical significance of the relationship with APS remains elusive. The pancreas, often overlooked, manifests in diverse ways, from pancreatitis to implications in diabetes. Adrenal insufficiency emerges as a common endocrine manifestation of APS, with adrenal hemorrhage or infarction being a presenting manifestation. Adrenal gland involvement has also been reported in the context of catastrophic APS. Pregnancy complications and infertility might be effects of APS on the female ovaries, while testicular torsion and decreased sperm concentration and total sperm count have been reported as rare effects of APS on male testes.


Subject(s)
Antiphospholipid Syndrome , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Female , Male , Pregnancy , Risk Factors , Prognosis , Pregnancy Complications/etiology , Pregnancy Complications/diagnosis , Endocrine System Diseases/diagnosis , Endocrine System Diseases/etiology , Pancreatic Diseases/etiology , Pancreatic Diseases/diagnosis
13.
Georgian Med News ; (349): 36-40, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38963198

ABSTRACT

Antiphospholipid syndrome (APS) is an acquired multisystem autoimmune disease characterized clinically by vascular thrombotic events, or pregnancy complications or nonthrombotic manifestations in the presence of persistently elevated antiphospholipid antibodies (aPL). We highlighted our case, which fulfills both the old APS classification criteria (1999,2006) _and the newest one (2023). The latest demonstrates very high specificity (99%) for APS diagnosis, compared to the older revised Sapporo criteria (86%). According to the new recommendation, the criteria are classified into 6 clinical and 2 laboratory domains, patient must accumulate at least 3 points from each clinical and laboratory domains. Our patient was diagnosed with antiphospholipid syndrome in 2018, as she had transient ischemic attack (TIA) without any changes on magnetic resonance tomography (MRI), and laboratory tests revealed triple positive antiphospholipid antibodies (12 points). Additional diagnostic tests were performed_thrombocytopenia, aortic valve thickening was noteworthy (4 points). Thus, TIA which had similar strength to stroke as the manifestation of arterial thrombosis by old guidelines, it is rejected according to the new recommendation, so the patient lost minimum 2 points; On the other hand, the current criteria added nonthrombotic events as weighted clinical domains, which gave the points to our patient. In conclusion we fully and highly specifically confirmed APS diagnosis as ACR/EULAR suggests.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Ischemic Attack, Transient , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/diagnostic imaging , Antiphospholipid Syndrome/blood , Antiphospholipid Syndrome/immunology , Female , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Ischemic Attack, Transient/diagnostic imaging , Ischemic Attack, Transient/diagnosis , Magnetic Resonance Imaging , Middle Aged , Adult
16.
Front Immunol ; 15: 1361519, 2024.
Article in English | MEDLINE | ID: mdl-39044818

ABSTRACT

Antiphospholipid syndrome (APS) is an autoimmune disease with arteriovenous thrombosis and recurrent miscarriages as the main clinical manifestations. Due to the complexity of its mechanisms and the diversity of its manifestations, its diagnosis and treatment remain challenging issues. Antiphospholipid antibodies (aPL) not only serve as crucial "biomarkers" in diagnosing APS but also act as the "culprits" of the disease. Endothelial cells (ECs), as one of the core target cells of aPL, bridge the gap between the molecular level of these antibodies and the tissue and organ level of pathological changes. A more in-depth exploration of the relationship between ECs and the pathogenesis of APS holds the potential for significant advancements in the precise diagnosis, classification, and therapy of APS. Many researchers have highlighted the vital involvement of ECs in APS and the underlying mechanisms governing their functionality. Through extensive in vitro and in vivo experiments, they have identified multiple aPL receptors on the EC membrane and various intracellular pathways. This article furnishes a comprehensive overview and summary of these receptors and signaling pathways, offering prospective targets for APS therapy.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Endothelial Cells , Antiphospholipid Syndrome/immunology , Humans , Antibodies, Antiphospholipid/immunology , Endothelial Cells/immunology , Endothelial Cells/metabolism , Animals , Signal Transduction , Biomarkers
17.
PeerJ ; 12: e17617, 2024.
Article in English | MEDLINE | ID: mdl-38948200

ABSTRACT

Antiphospholipid syndrome (APS) is a systemic autoimmune syndrome characterized by arterial or venous thrombosis, pregnancy complications and thrombocytopenia. The aim of this study is to investigate the association between APS and atrial fibrillation (AF) among patients in Peking University People's Hospital. A single center retrospective study was conducted. Cases were hospitalized patients diagnosed with AF by a cardiologist while the control group patients did not exhibit cardiac diseases. The results of the study revealed that in multivariable logistic regression, APS, anticardiolipin antibody (aCL) positivity and anti-beta-2-glycoprotein antibody (anti-ß2GPI) positivity are independent risk factors of AF. APS, aCL positivity and anti-ß 2GPI positivity are statistically different between AF patients and non-AF patients. Forthcoming studies are needed to clarify the potential link between APS and AF.


Subject(s)
Antiphospholipid Syndrome , Atrial Fibrillation , Humans , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/immunology , Retrospective Studies , Female , Atrial Fibrillation/epidemiology , Atrial Fibrillation/etiology , Male , Middle Aged , Case-Control Studies , Risk Factors , Antibodies, Anticardiolipin/blood , Adult , Aged , beta 2-Glycoprotein I/immunology , China/epidemiology
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 605-611, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38948271

ABSTRACT

Objective: To determine the humoral immunity in advanced maternal-age women with recurrent spontaneous abortion (RSA). Methods: A retrospective study was performed between January 2022 and October 2023 in the Department of Reproductive Immunity of Shanghai First Maternity and Infant Hospital. Women with RSA were recruited and multiple autoantibodies were tested. Multivariate logistic regression was performed to compare the associations between different age groups (20 to 34 years old in the low maternal-age group and 35 to 45 years in the advanced maternal-age group) and multiple autoantibodies, while controlling for three confounding factors, including body mass index (BMI), previous history of live birth, and the number of spontaneous abortions. Then, we investigated the differences in the humoral immunity of advanced maternal-age RSA women and low maternal-age RSA women. Result: A total of 4009 women with RSA were covered in the study. Among them, 1158 women were in the advanced maternal-age group and 2851 women were in the low maternal-age group. The prevalence of antiphospholipid syndrome, systemic lupus erythematosus, Sjogren's syndrome, rheumatoid arthritis, and undifferentiated connective tissue disease was 15.6% and 14.1%, 0.0% and 0.1%, 0.9% and 0.9%, 0.3% and 0.0%, and 23.7% and 22.6% in the advanced maternal-age group and low maternal-age group, respectively, showing no statistical difference between the two groups. The positive rates of antiphospholipid antibodies (aPLs), antinuclear antibody (ANA), extractable nuclear antigen (ENA) antibody, anti-double stranded DNA (dsDNA) antibody, anti single-stranded DNA (ssDAN) antibody, antibodies against alpha-fodrin (AAA), and thyroid autoimmunity (TAI) were 19.1% and 19.5%, 6.6% and 6.6%, 9.2% and 10.5%, 2.0% and 2.0%, 2.2% and 1.2%, 5.1% and 4.9%, and 17.8% and 16.8%, respectively. No differences were observed between the two groups. 1.6% of the women in the advanced maternal-age group tested positive for lupus anticoagulant (LA), while 2.7% of the women in the low maternal-age group were LA positive, with the differences being statistically significant (odds ratio=0.36, 95% confidence interval: 0.17-0.78). In the 4008 RSA patients, the cumulative cases tested positive for the three antibodies of the aPLs spectrum were 778, of which 520 cases were positive for anti-ß2 glycoprotein Ⅰ antibodies (ß2GPⅠ Ab)-IgG/IgM, 58 were positive for aCL-IgG/IgM, 73 were positive for LA, 105 were positive for both ß2GPⅠ Ab-IgG/IgM and aCL-IgG/IgM, 17 were positive for both ß2GPⅠ Ab-IgG/IgM and LA, 2 were positive for both aCL-IgG/IgM and LA, and 3 were positive for all three antibodies. Conclusion: Our study did not find a difference in humoral immunity between RSA women of advanced maternal age and those of low maternal age.


Subject(s)
Abortion, Habitual , Autoantibodies , Immunity, Humoral , Maternal Age , Humans , Female , Adult , Abortion, Habitual/immunology , Retrospective Studies , Pregnancy , Autoantibodies/blood , Autoantibodies/immunology , Middle Aged , Antiphospholipid Syndrome/immunology , China , Lupus Erythematosus, Systemic/immunology , Sjogren's Syndrome/immunology , Young Adult , Antibodies, Antinuclear/blood , Antibodies, Antinuclear/immunology , Arthritis, Rheumatoid/immunology , Undifferentiated Connective Tissue Diseases/immunology , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Logistic Models
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 513-520, 2024 May 20.
Article in Chinese | MEDLINE | ID: mdl-38948301

ABSTRACT

Obstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with various pathological pregnancies, such as recurrent miscarriage, stillbirth, severe pre-eclampsia and severe placental insufficiency. The persistent presence of antiphospholipid antibodies (aPLs) is the most important laboratory characteristic of OAPS. OAPS severely affects the reproductive health of women of childbearing age in China. Reports indicate that approximately 9.6% stillbirths, 11.5% severe pre-eclampsia, and 54% recurrent miscarriages are associated with OAPS or aPLs. However, the pathogenesis of OAPS remains unclear. Previously, thrombosis at the maternal-fetal interface (MFI) was considered the main mechanism of OAPS-related pathological pregnancies. Consequently, the use of low molecular weight heparin and aspirin throughout pregnancy was recommended to improve outcomes in OAPS patient. In recent years, many studies have found that thrombosis in MFI is uncommon, but various inflammatory factors are significantly increased in the MFI of OAPS patients. Based on these findings, some clinicians have started using anti-inflammatory treatments for OAPS, which have preliminarily improved the pregnancy outcomes. Nevertheless, there is no consensus on these second-line treatments of OAPS. Another troubling issue is the clinical diagnosis of OAPS. Similar to other autoimmune diseases, there are only classification criteria for OAPS, and clinical diagnosis of OAPS depends on the clinicians' experience. The present classification criteria of OAPS were established for clinical and basic research purposes, not for patient clinical management. In clinical practice, many patients with both positive aPLs and pathological pregnancy histories do not meet the strict OAPS criteria. This has led to widespread issues of incorrect diagnosis and treatment. Timely and accurate diagnosis of OAPS is crucial for effective treatment. In this article, we reviewed the epidemiological research progress on OAPS and summarized its classification principles, including: 1) the persistent presence of aPLs in circulation; 2) manifestations of OAPS, excluding other possible causes. For the first point, accurate assessment of aPLs is crucial; for the latter, previous studies regarded only placenta-related pregnancy complications as characteristic manifestations of OAPS. However, recent studies have indicated that adverse pregnancy outcomes related to trophoblast damage, such as recurrent miscarriage and stillbirth, also need to be considered in OAPS. We also discussed several key issues in the diagnosis and treatment of OAPS. First, we addressed the definition of non-standard OAPS and offered our opinion on defining non-standard OAPS within the framework of the 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) APS criteria. Then, we discussed the advantages and disadvantages of different aPL testing methods, emphasizing that harmonizing results across platforms and establishing specific reference values are keys to resolving controversies in aPL testing results. We also introduced the application of non-criteria aPLs, especially anti-phosphatidylserine/prothrombin antibody (aPS/PT) and anti-ß2 glycoprotein Ⅰ domain Ⅰ antibody (aß2GPⅠDⅠ). Additionally, we discussed aPL-based OAPS risk classification strategies. Finally, we proposed potential treatment methods for refractory OAPS. The goal is to provide a reference for the clinical management of OAPS.


Subject(s)
Antiphospholipid Syndrome , Pregnancy Complications , Humans , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/therapy , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/complications , Pregnancy , Female , Pregnancy Complications/diagnosis , Pregnancy Complications/therapy , Abortion, Habitual/etiology , Abortion, Habitual/immunology , Abortion, Habitual/diagnosis , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Heparin, Low-Molecular-Weight/therapeutic use , Aspirin/therapeutic use , Pre-Eclampsia/diagnosis , Pre-Eclampsia/therapy , Pre-Eclampsia/etiology
20.
Ceska Gynekol ; 89(3): 237-244, 2024.
Article in English | MEDLINE | ID: mdl-38969520

ABSTRACT

AIM AND METHODOLOGY: To provide a comprehensive review on new findings and current recommendations regarding antiphospholipid antibodies with particular emphasis on clinical impact on gestation. CONCLUSION: Antiphospholipid antibodies are an important risk factor for the development of a series of pregnancy-related complications. Early diagnosis and appropriate therapy can reduce the incidence of pregnancy loss and pregnancy-related complications.


Subject(s)
Antibodies, Antiphospholipid , Antiphospholipid Syndrome , Pregnancy Complications , Humans , Pregnancy , Female , Antibodies, Antiphospholipid/blood , Antibodies, Antiphospholipid/immunology , Antiphospholipid Syndrome/immunology , Antiphospholipid Syndrome/diagnosis , Antiphospholipid Syndrome/complications , Pregnancy Complications/immunology
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