Antiphospholipid antibodies and their clinical significance

2021 ◽  
Author(s):  
Ф.А. Чельдиева ◽  
Т.М. Решетняк ◽  
А.М. Лила
Keyword(s):  
Clinical Significance ◽  
Antiphospholipid Antibodies ◽  
Solid Phase ◽  
Clinical Signs ◽  
Anticardiolipin Antibodies ◽  
Positive Test Result ◽  
Recurrent Thrombosis ◽  
Vascular Thrombosis ◽  
Iga Antibodies ◽  
Test Result

Обзор посвящён антифосфолипидным антителам (аФЛ) и их клинико-диагностической ценности. Рассматриваются вопросы стандартизации методов исследования аФЛ, в частности твердофазных тест-систем, одним из представителей которых является хемилюминесцентый анализ. Обсуждаются патогенетические аспекты антифосфолипидного синдрома (АФС) и описываются пути влияния аФЛ на различные компоненты гемостаза. Дается подробная характеристика β2-гликопротеина 1 (β2-ГП1) с описанием доменов. Подробно изучены клинические проявления и взаимосвязь «экстра»-критериальных аФЛ: IgA антител к кардиолипину (IgA-аКЛ), IgA антител к β2-ГП1 (IgA-аβ2-ГП1), антител к домену I β2-ГП1 (аβ2-ГП1-DI), антител к комплексу фосфатидилсерин–протромбин и аФЛ, не входящих в Сиднейские диагностические критерии АФС. Antiphospholipid syndrome (APS) is an acquired autoimmune thrombophilia in which patients have clinical signs of recurrent thrombosis and morbidity during pregnancy and constantly test positive for antibodies against phospholipid (aPL). At least one clinical (vascular thrombosis or pregnancy) and one laboratory (positive test result for anticoagulant lupus, anticardiolipin antibodies and/or anti-β2-glycoprotein 1 antibodies) must be performed in order for the patient to be classified as having APS. However, the clinical and laboratory APS spectra cover additional manifestations. Research interest is increasingly focused on developing new assays that may be more specifi c to APS than current aPL tests. This review focuses on extra criterion antiphospholipid antibodies — IgA antibodies to cardiolipin (IgA-aCL), IgA antibodies to β2-glycoprotein 1 (IgA-aβ2-GP1), antibodies to phosphatidylserine-prothrombin complex. A detailed description of aβ2-GP1 with a description of domains is given. The questions of standardization of aPL research methods, in particular, solid-phase test systems, one of which is chemiluminescent analysis, are examined.

scholarly journals Antiphospholipid Antibodies in Women Undergoing In Vitro Fertilization Treatment: Clinical Value of IgA Anti-β2glycoprotein I Antibodies Determination

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Odile Paulmyer-Lacroix ◽  
Laura Despierres ◽  
Blandine Courbiere ◽  
Nathalie Bardin
Keyword(s):  
In Vitro Fertilization ◽  
Antiphospholipid Antibodies ◽  
Therapeutic Strategy ◽  
Embryo Implantation ◽  
Anticardiolipin Antibodies ◽  
Clinical Value ◽  
Vitro Fertilization ◽  
Total Prevalence ◽  
Iga Antibodies

Implantation failure could be related to antiphospholipid antibodies (aPL). We retrospectively analyzed the usefulness of aPL determination in women undergoing IVF. Conventional aPL of the antiphospholipid syndrome, lupus anticoagulant (LA), anticardiolipin antibodies (aCL), anti-β2glycoprotein I (aβ2GPI) antibodies, and IgG and IgM isotypes as well as IgA isotype were analyzed in women presenting with at least two implantation failures after in vitro fertilization (IVF). In a population of 40 IVF patients, a total prevalence of 20% (8/40) of aPL was found, significantly different from that of the control population (100 healthy blood donors,P<0.0005). Among the panels of aPL tested, aβ2GPI IgA antibodies were the most prevalent (62.5% 5/8), significantly higher in IVF patients (12.5%, 5/40) than in controls (1%, 1/100) (P=0.01). No difference according to the numbers of IVF attempts and success of embryo implantation was found between aPL positive and negative IVF patients. In contrast, no accomplished pregnancy with full-term live birth was observed in aPL positive IVF patients. Altogether our data led us to propose aPL assessment, in particular aβ2GPI IgA antibodies, in support of IVF treated women. In a perspective way, an early aPL detection could be the basis for defining novel therapeutic strategy.

Antiphosphatidylinositol Antibody in Deep Venous Thrombosis Patients

2003 ◽  
Vol 16 (1) ◽  
pp. 61-66 ◽  
Author(s):  
P. Panarelli ◽  
M.P. Viola-Magni ◽  
E. Albi
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Solid Phase ◽  
Protein Complexes ◽  
Anticardiolipin Antibodies ◽  
Anionic Phospholipids ◽  
Positive Antibody

Antiphospholipid antibodies are a heterogeneous group of immunoglobulins with specificity for a number of phospholipids, phospholipid-binding proteins and phospholipid-protein complexes. The association between antiphospholipid antibodies and a variety of pathologic disorders, such as arterial and venous thrombosis and recurrent pregnancy loss is recognized as Antiphospholipid Syndrome. The immunoassay currently used to detect antiphospholipid antibodies is the anticardiolipin test. Anticardiolipin antibodies are believed to be polyspecific antibodies that cross-react with all the anionic phospholipids. Therefore, testing only for anticardiolipin antibodies does not always permit detection of all antiphospholipid antibodies, specially when only IgG are evaluated. In a selected population of 74 idiopathic and secondary deep venous thrombosis patients, IgG anticardiolipin, antiphosphatidylinositol and antiphosphatidylserine antibodies were detected by solid-phase immunoassays. Our results show that by testing for each antiphospholipid family, many patients, not evidenced by the standard anticardiolipin assay, were found to be antiphospholipid-positive. The anticardiolipin positive patients have always low, moderate or high levels of antiphospholipid antibodies, suggesting that the antiphospholipid positivity is predictive of anticardiolipin positivity. It should be noted that the patients with only antiphosphatidylinositol positive antibody have a story of nervous system pathology. The meaning of these results is at present under discussion.

scholarly journals Laboratory methods to detect antiphospholipid antibodies

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 321-328 ◽  
Author(s):  
Steven A. Krilis ◽  
Bill Giannakopoulos
Keyword(s):  
Clinical Significance ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Evidence Based ◽  
Diagnostic Utility ◽  
Laboratory Methods ◽  
Detailed Review ◽  
Glycoprotein I ◽  
Beta 2

Abstract This chapter reviews several important themes pertaining to the antiphospholipid syndrome (APS), including a description of the clinical features, a discussion of the main autoantigen, beta 2-glycoprotein I (β2GPI), and insights into the characteristics of the pathogenic anti-β2GPI autoantibodies. Evidence-based considerations for when to test for APS are explored, along with the clinical significance of patients testing positive on multiple APS assays, so-called triple positivity. A detailed review of recently published laboratory guidelines for the detection of lupus anticoagulant and the solid-phase anticardiolipin and anti-β2GPI ELISAs is undertaken. Finally, a brief review of nonclassification criteria laboratory assays with potential future diagnostic utility is presented.

Standardization of Antiphospholipid Antibody Testing—Historical Perspectives and Ongoing Initiatives

2014 ◽  
Vol 40 (02) ◽  
pp. 172-177 ◽  
Author(s):  
Rohan Willis ◽  
Gabriella Lakos ◽  
E. Harris
Keyword(s):  
Clinical Significance ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Task Force ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antibody Testing ◽  
Historical Perspectives ◽  
The Past ◽  
Glycoprotein I

The measurement of antiphospholipid antibodies (aPL) has been an important aspect of antiphospholipid syndrome (APS) characterization since the disease was first described in the 1980s. Despite significant efforts geared toward the standardization of immunoassays that measure anticardiolipin antibodies and anti-β2-glycoprotein I spanning three decades, there are still reports of significant interassay and interlaboratory variation in the results of these assays. At the recent 13th International Congress on Antiphospholipid Antibodies (APLA 2010, April 13–16, 2010, Galveston, TX), a task force composed of internationally recognized experts in the field of APS was formed to address these issues. In this review, we discuss approaches that have been used in the past to achieve harmonization among aPL immunoassays as well as the ongoing efforts of the APLA task force. Our review also highlights the importance of cutoff determination in aPL assays and the clinical significance of positive aPL results of varying magnitudes.

scholarly journals Recent advances in understanding antiphospholipid syndrome

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2908 ◽  
Author(s):  
Maria Laura Bertolaccini ◽  
Giovanni Sanna
Keyword(s):  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Anticardiolipin Antibodies ◽  
Coagulation Cascade ◽  
Systemic Autoimmune Disease ◽  
Vascular Thrombosis ◽  
Clinical Criteria ◽  
Pregnancy Morbidity ◽  
Glycoprotein I ◽  
Hughes Syndrome

Antiphospholipid syndrome (APS), also known as Hughes Syndrome, is a systemic autoimmune disease characterized by thrombosis and/or pregnancy morbidity in the presence of persistently positive antiphospholipid antibodies. A patient with APS must meet at least one of two clinical criteria (vascular thrombosis or complications of pregnancy) and at least one of two laboratory criteria including the persistent presence of lupus anticoagulant (LA), anticardiolipin antibodies (aCL), and/or anti-b2 glycoprotein I (anti-b2GPI) antibodies of IgG or IgM isotype at medium to high titres in patient’s plasma. However, several other autoantibodies targeting other coagulation cascade proteins (i.e. prothrombin) or their complex with phospholipids (i.e. phosphatidylserine/prothrombin complex), or to some domains of β2GPI, have been proposed to be also relevant to APS. In fact, the value of testing for new aPL specificities in the identification of APS in thrombosis and/or pregnancy morbidity patients is currently being investigated.

scholarly journals COVID-19 and Antiphospholipid Antibodies: Time for a Reality Check?

2021 ◽  
Author(s):  
Emmanuel J. Favaloro ◽  
Brandon Michael Henry ◽  
Giuseppe Lippi
Keyword(s):  
Antiphospholipid Antibodies ◽  
Solid Phase ◽  
High Titer ◽  
Severe Form ◽  
Anticardiolipin Antibodies ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Glycoprotein I ◽  
Autoimmune Conditions ◽  
Antiprothrombin Antibodies

AbstractAntiphospholipid antibodies (aPL) comprise a panel of autoantibodies that reflect a potential prothrombotic risk in several autoimmune conditions, most notably antiphospholipid (antibody) syndrome (APS). aPL can be divided into those that form part of the laboratory criteria for APS, namely, lupus anticoagulant (LA), as well as anticardiolipin antibodies (aCL) and anti-β2-glycoprotein I antibodies (aβ2GPI) of the immunoglobulin G and M classes, and those that form a group considered as “noncriteria antibodies.” The noncriteria antibodies include, for example, antiphosphatidylserine antibodies (aPS), antiprothrombin antibodies (aPT), and antiphosphatidylserine/prothrombin complex antibodies (aPS/PT). COVID-19 (coronavirus disease 2019) represents a prothrombotic disorder, and there have been several reports of various aPL being present in COVID-19 patients. There have also been similarities drawn between some of the pathophysiological features of COVID-19 and APS, in particular, the most severe form, catastrophic APS (CAPS). In this review, we critically appraise the literature on aPL and COVID-19. This is a companion piece to a separate review focused on LA. In the current review, we primarily concentrate on the so-called solid phase identifiable aPL, such as aCL and aβ2GPI, but also reflect on noncriteria aPL. We conclude that aPL positivity may be a feature of COVID-19, at least in some patients, but in general, identified “solid-phase” aPL are of low titer and not able to be well-linked to the thrombotic aspects of COVID-19. Also, most publications did not assess for aPL persistence, and where persistence was checked, the findings appeared to represent transient aPL. Importantly, high-titer aPL or multiple aPL positivity (including double, triple) were in the minority of COVID-19 presentations, and thus discount any widespread presence of APS, including the most severe form CAPS, in COVID-19 patients.

Prevalence and Clinical Significance of Elevated Antiphospholipid Antibodies in Adults with Immune Thrombocytopenic Purpura.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1083-1083 ◽  
Author(s):  
Carole Pierrot-Deseilligny ◽  
Mehdi Khellaf ◽  
Michele Gouault ◽  
Liliane Intrator ◽  
Marc Michel ◽  
...  
Keyword(s):  
Platelet Count ◽  
Clinical Significance ◽  
Immune Thrombocytopenic Purpura ◽  
Antiphospholipid Antibodies ◽  
Previous History ◽  
Anticardiolipin Antibodies ◽  
Hazard Ratio ◽  
Primary Antiphospholipid Syndrome ◽  
Newly Diagnosed ◽  
Thrombocytopenic Purpura

Abstract Background: The clinical and pathogenic significances of the presence of antiphospholipid antibodies (APA) [anticardiolipin antibodies (aCL) and lupus-like anticoagulant (LA)] in patients with immune thrombocytopenic purpura (ITP) remain controversial. Objective: To determine the prevalence and clinical significance of positive APA in a large monocentric cohort of adults with newly diagnosed ITP. Methods: aCL (IgG and IgM) and LA were searched at time of diagnosis in 260 adults with ITP and a platelet count < 50×109/L over a 15 years period. Thirty-five patients with definite systemic lupus, 5 with primary antiphospholipid syndrome and 4 with HIV infection were excluded and the analysis was performed on 216 patients. Results: APA (aCL and LA) were detected at ITP diagnosis in 55 patients (25%) including: IgG-aCL in 43 patients (20%) with a level between 15-39 UI/L in 31 and ≥40UI/l in 12; IgM-aCL in 11 patients (5%); and LA in 16 patients (7%). LA was associated with IgG-aCL in 14 patients, IgM-aCL in 1 patient, and was isolated in 1 patient. Positive test for LA was correlated with the presence of highly positive IgG-aCL (≥40UI/L) (p=0.001). Age, gender, initial platelet count, acute or chronic outcome of ITP were not associated with the presence of APA (aCL and LA), aCL and LA status except for age which was lower in LA positive group (mean age 22 years vs 42 years in LA negative group, p=0.002). After a median follow-up of 31 months (range: 1 to 185 months), 15/216 (7%) patients experienced a thrombosis (arterial = 3, deep venous thrombosis and/or pulmonary embolism = 12); 5 of whom (33%) had positive aCL (with a level ≥ 40 UI/L in 4). In 4 of these 5 patients, aCL were associated with positive LA. In multivariate analysis, thrombosis events were associated with age [Hazard ratio = 1.5 (IC95% : 1.1–2.0], presence of LA [Hazard ratio = 6.5 (IC95% : 1.7–25.5] or presence of IgG-aCL at high level (≥40UI/L) [Hazard ratio = 6.1 (IC95% : 1.6–23.7]. In contrast, there was no association of thrombosis events with sex, platelet count at diagnosis, acute or chronic evolution (≥ 6 months), antinuclear antibodies or treatments used. Conclusions: Prevalence of APA (25%) in adults with newly diagnosed ITP is lower in our cohort than previously observed in other studies. Though the incidence of thrombosis is significantly increased in patients with LA and/or highly positive aCL, this risk seems too low to recommend a systematic testing in patients with ITP and no previous history of thrombosis.

Clinical significance of different antiphospholipid antibodies in the WAPS (warfarin in the antiphospholipid syndrome) study

Blood ◽  
2007 ◽  
Vol 110 (4) ◽  
pp. 1178-1183 ◽  
Author(s):  
Monica Galli ◽  
Giovanna Borrelli ◽  
Eva Marie Jacobsen ◽  
Rosa Maria Marfisi ◽  
Guido Finazzi ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Significance ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
Protein S ◽  
Anticardiolipin Antibodies ◽  
Antibody Detection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igm Antibodies ◽  
Glycoprotein I

Abstract To assess the clinical significance of lupus anticoagulants (LAs) and antiphospholipid antibodies (aPLs) toward thrombosis and abortions, we measured them in 112 patients whose samples were available at enrollment in the warfarin in the antiphospholipid syndrome (WAPS) study. Enzyme-linked immunosorbent assay (ELISA) and coagulation test values in the highest and lowest tertiles were compared. When considered separately, IgG antibodies to β2-glycoprotein I (aβ2GPI) and prothrombin (aPT) were associated with anamnestic arterial and venous thrombosis, respectively, and those to annexin AV (aAnAV) with abortions. IgM antibodies to protein S and the lupus ratio of the dilute prothrombin time were associated with prospective thrombosis. No other association for IgM antibodies was seen. LA-positive patients who carried aβ2GPI antibodies were at risk of anamnestic arterial and total thrombosis and aPT antibodies to that of anamnestic venous and total thrombosis. LA-positive patients who carried IgG aβ2GPI and aAnAV antibodies were at risk for both anamnestic abortion and prospective thrombosis. Overall, these data support the inclusion of aβ2GPI antibodies in and suggest the removal of anticardiolipin antibodies from the laboratory criteria of the antiphospholipid syndrome. They also suggest that the measurement of aPT and aAnAV antibodies is useful in some selected situations and that there is little role for IgM antibody detection.

Antiphospholipid Antibodies: Prevalence, Clinical Significance and Correlation to Cytokine Levels in Acute Myeloid Leukemia and Non-Hodgkin’s Lymphoma

1993 ◽  
Vol 70 (04) ◽  
pp. 568-572 ◽  
Author(s):  
Roberto Stasi ◽  
Elisa Stipa ◽  
Mario Masi ◽  
Felicia Oliva ◽  
Alessandro Sciarra ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Significance ◽  
Antiphospholipid Antibodies ◽  
Myeloid Leukemia ◽  
Hodgkin’S Lymphoma ◽  
Hodgkin's Lymphoma ◽  
Tnf Alpha ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Acute Myeloid

SummaryThis study was designed to explore the prevalence and clinical significance of elevated antiphospholipid antibodies (APA) titres in patients affected by acute myeloid leukemia (AML) and highgrade non-Hodgkin’s lymphoma (NHL). We also analyzed possible correlations with circulating levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and the soluble form of the receptor for interleukin-2 (sIL-2r). Nineteen patients with de novo AML and 14 patients with newly-diagnosed NHL were investigated. Tests for APA included the measurement of anticardiolipin antibodies (ACA) with a solid-phase immunoassay, and the detection of the lupus-like anticoagulant (LA) activity. Five patients with AML (26.3%) and 5 patients with NHL (35.7%) presented elevated APA at diagnosis, as compared to 3 of 174 persons of the control group (p <0.0001). APA titres became normal in all patients responding to treatment, whereas nonresponders retained elevated levels. In addition, 6 patients (4 with AML and 2 with NHL), who had normal APA at diagnosis and were either refractory to treatment or in relapse, subsequently developed LA and/or ACA positivity. At presentation, the mean levels of IgG- and IgM-ACA in patients were not significantly different from Controls, and concordance between ACA and LA results reached just 30%. With regard to the clinical course, we were not able to detect any statistically significant difference between patients with normal and elevated APA. Pretreatment concentrations of IL-6 and TNF-alpha in AML, and sIL-2r in NHL were found significantly elevated compared to Controls (p = 0.003, p = 0.009 and p = 0.024 respectively). In addition, the levels of these cytokines correlated with IgG-ACA at the different times of laboratory investigations. These results demonstrate that APA may have a role as markers of disease activity and progression in some haematological malignancies.

The clinical relevance of isolated lupus anticoagulant positivity in patients with thrombotic antiphospholipid syndrome

2020 ◽  
Author(s):  
Dong-mei Yin ◽  
Philip de Groot ◽  
Marisa Ninivaggi ◽  
Katrien M.J. Devreese ◽  
Bas de Laat
Keyword(s):  
Antiphospholipid Syndrome ◽  
Clinical Relevance ◽  
Antiphospholipid Antibodies ◽  
Odds Ratio ◽  
Lupus Anticoagulant ◽  
Solid Phase ◽  
Control Group ◽  
Domain I ◽  
Normal Controls ◽  
Better Than

Background: Patients positive for three types of antiphospholipid antibodies (aPLs) (triple positivity) have been identified at a high risk for thrombotic events. However, the clinical significance of isolated lupus anticoagulant (LAC) positivity is debated. Objectives: To investigate the clinical relevance of isolated LAC. Patients/Methods 456 patients were enrolled in this study; 66 antiphospholipid syndrome patients and 390 control patients. The control group existed of autoimmune patients (n=91), patients with thrombosis but without aPLs (n=127) and normal controls (n=172). The criteria LAC, anti-cardiolipin (anti-CL) and anti-beta2glycoprotein I (anti-β2GPI) IgG and IgM and the non-criteria IgA anti-CL and anti-β2GPI, anti-domain I (anti-DI) of β2GPI IgG and anti-phosphatidylserine/prothrombin (anti-PS/PT) IgG and IgM were detected according to the ISTH guidelines for solid phase assays. Results: 70 patients were positive for LAC, of which 44 were negative for both anti-β2GPI and anti-CL. We found that isolated LAC proved to be strongly associated with vascular thrombosis (Odds ratio (OR) (95% CI) 7.3 (3.3-16.1)), even better than triple positive samples (OR 4.3 (1.6-12.2)). The titers of the anti-PS/PT IgG and IgM were significantly higher in triple positivity samples compared to samples with isolated LAC positivity. The majority of single LAC positives were anti-PS/PT negative. We observed that LAC positivity was weaker in isolated LAC positive patients compared to LAC activity in triple positive patients. Conclusions: Isolated LAC was highly associated with thrombosis. The presence of anti-PS/PT could not explain LAC positivity in isolated LAC. Isolated LAC showed a weaker LAC activity compared to triple positive patients.

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