Role of antiphospholipid score and anti-β2-glycoprotein I Domain I autoantibodies in the diagnosis of antiphospholipid syndrome

Mondéjar, Rebeca; González-Rodríguez, Concepción; Miera, F. Javier Toyos-Sáenz de; Melguizo-Madrid, Enrique; Zohoury, Navid; Mähler, Michael; Losquiño, I. Romero; Fabiani, F.

doi:10.1016/j.cca.2014.01.047

Cited by 33 publications

(40 citation statements)

References 28 publications

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“…Two such systems that are based on testing a profile of antibodies and providing an algorithm for scoring the patient's antibody profile have been proposed; namely, the Global Anti-Phospholipid Syndrome Score (GAPSS) and the antiphospholipid score (aPL-S) 29,30 . A number of secondary studies have verified the usefulness of each of these respective approaches and the task force in 2014 suggested there is clinical utility in assessing multiple aPL positivity 31,32,33,34,35 . Notably, both the GAPSS and the aPL-S scoring systems require the specific measurement of aPS/PT antibodies (not antiprothrombin in solid phase-aPT) in addition to the criteria markers of LAC, aCL, and anti-β 2 -GPI antibodies.…”

Section: Rheumatologymentioning

confidence: 99%

Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies

Zohoury

Bertolaccini²,

Rodríguez-García³

et al. 2017

J Rheumatol

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Objective.Most clinicians use the 2006 Sydney classification criteria to evaluate patients suspected of having antiphospholipid syndrome (APS). Although sensitive and specific for APS, many patients fulfilling clinical criteria for the syndrome are persistently negative for the specific serological tests (“laboratory criteria”). These “seronegative APS” (SN-APS) patients can go undiagnosed and untreated until they experience serious clinical events. This study’s objective was to describe antibody profiles of SN-APS patients using non-criteria markers, assess the clinical utility of these markers separately and in combination, and suggest incorporation into guidelines for patients suspected of APS.Methods.We categorized 175 consecutive patients suspected of APS into 2 subgroups: 107 fulfilling Sydney APS classification for seropositive APS (SP-APS) and 68 with clinical manifestations suggestive of APS but having negative serology, on 2 occasions, for criteria markers (SN-APS). On study inclusion, samples were retested for criteria and 11 non-criteria markers, including antiphosphatidylserine/prothrombin antibodies.Results.Using 4 of 11 non-criteria tests, a cumulative 30.9% of SN-APS patients were detected. Combining results of all 11 non-criteria tests, 25 SN-APS (36.8%) and 89 SP-APS (83.2%) were positive for 1 or more non-criteria antibodies.Conclusion.Failure to diagnose APS can result in severe clinical consequences. Patients displaying clinical features of APS, but negative for conventional criteria markers, should undergo additional testing for non-criteria biomarkers. In our cohort, around one-third of SN-APS patients showed reactivity to 1 or more non-criteria markers. An update to the current classification criteria incorporating new serological markers should be considered to identify and stratify patients with APS for more effective treatment and management.

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Section: Rheumatologymentioning

confidence: 99%

Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies

Zohoury

Bertolaccini²,

Rodríguez-García³

et al. 2017

J Rheumatol

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“…[25][26][27][28][29][30][31] Subsequent studies documented that anti-DI autoantibodies, being much less frequent in control populations in which antibodies against the whole molecule can be detected, provide good specificity for APS or systemic autoimmune conditions. 32,33 The opposite seems to be true for IgG antibodies against DIV-V, which are more frequent in asymptomatic aPL carriers, in patients with leprosy, in children suffering from atopic dermatitis or born from mothers affected by systemic autoimmune disorders.…”

Section: Epitope Specificity Of Anti-b2gpi Antibodies: the New Aspectmentioning

confidence: 99%

“…32,33 Anti-DI antibodies have been associated with both arterial and venous thrombosis with a significant increase in the odds ratio for these events. [25][26][27][30][31][32] However, the fact that the antibodies are usually detectable in patients double or triple positive for the APS laboratory classification tests and their strong association with LA positivity raise the issue whether the predictive power is dependent on this antibody subpopulation itself or simply on their presence in patients with high risk aPL profiles. Anti-DI antibodies have also been described in obstetric APS patients (even in pure obstetric patients without vascular events), although with lower prevalence and in some reports with lower titres.…”

Section: Epitope Specificity Of Anti-b2gpi Antibodies: the New Aspectmentioning

confidence: 99%

Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools

Meroni

2016

Lupus

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Beta-2 glycoprotein I (b2GPI) is the main antigenic target for anti-phospholipid antibodies (aPL), the serological markers of anti-phospholipid syndrome (APS). Conformational changes of the molecule seem to be essential for exposing the cryptic epitope for aPL binding and to trigger pathogenic pathways. There is increasing evidence that a conformational epitope located in the Domain I (DI) of the molecule is the main epitope targeted by human autoantibodies. The pathogenic role of the DI epitope has been recently supported by in vivo models and by immuno-histopathological findings in APS patients. Antibodies targeting b2GPI-DI are more frequently detected in patients with full-blown APS compared to asymptomatic aPL carriers or patients with infectious diseases who have antibodies directed against the whole molecule. Anti-DI antibodies are positively correlated with medium to high titres of aPL, with the presence of lupus anticoagulant and thrombotic and pregnancy manifestations, enabling identification of patients at higher risk of clinical events. However, some APS patients develop antibodies reacting against b2GPI epitopes other than DI, suggesting that other anti-b2GPI antibody subsets may be clinically relevant. Although preliminary results suggest that anti-DI antibodies can be detected by different assays in a comparable manner, further prospective studies are needed to support their use in the clinical setting and their predictive value. Lupus (2016) 25, 905-910.

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“…The principle and protocol of the QUANTA Flash assay system has been previously described. [12][13][14] The relative light units (RLUs) are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which in turn is proportional to the amount of anti-b 2 GPI-D1 antibodies bound to the antigen on the beads. Samples above the analytical measuring range were diluted by auto-rerun feature to determine the exact concentration of antib 2 GPI-D1 antibodies.…”

Section: Autoantibody Assaysmentioning

confidence: 99%

Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome

Mähler

Albesa

Zohoury

et al. 2016

Lupus

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Introduction: Antibodies to the domain 1 of beta 2 glycoprotein I (b 2 GPI-D1) have been suggested as a risk marker for thrombosis in patients with the antiphospholipid syndrome (APS). This cross-sectional study aimed to analyze the clinical utility of a novel chemiluminescence assay for the detection of anti-b 2 GPI-D1 antibodies. Patients and methods: Sera collected from patients with primary or secondary APS (n ¼ 106; 72 with and 34 without history of thrombosis) and controls (n ¼ 272) were tested for anti-b 2 GPI-D1 IgG by chemiluminescence assay (QUANTA Flash) and by two anti-b 2 GPI IgG assays (QUANTA Lite and QUANTA Flash b 2 GPI IgG). Results: Anti-b 2 GPI-D1 IgG titers were significantly higher in patients with thrombosis (P ¼ 0.0032) than those without. At the cut-off of 20 units, which yielded a 99.5% specificity, 24 of 72 (34.9%) patients with thrombosis and four of 34 (11.8%) without thrombosis were anti-b 2 GPI-D1 IgG positive (odds ratio, OR ¼ 4.0). By further optimizing the cut-off specifically for correlation with thrombosis, 20.8% of the patients with thrombosis and 2.9% of the patients without thrombosis were positive (OR ¼ 8.7). The ORs were significantly lower for antibodies to the full-length b 2 GPI by either the chemiluminescence assay or ELISA. Using the anti-b 2 GPI chemiluminescence assay, the OR was 2.3 (recommended cut-off of 20 CU) or 4.1 (optimal cut-off 164.6 CU). Using the anti-b 2 GPI ELISA, the OR was 2.7 (recommended cut-off of 20 units) or 3.7 (optimal cut-off 7.6 units). Conclusion: These data indicate that anti-b 2 GPI-D1 IgG are present more frequently and in higher titers in APS patients with thrombotic complications than in those without.The novel b 2 GPI-D1 chemiluminescence assay appears to be superior to full-length b 2 GPI assays for the risk assessment of thrombotic events in APS patients. Lupus (2016) 25, 911-916.

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Role of antiphospholipid score and anti-β2-glycoprotein I Domain I autoantibodies in the diagnosis of antiphospholipid syndrome

Cited by 33 publications

References 28 publications

Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies

Closing the Serological Gap in the Antiphospholipid Syndrome: The Value of “Non-criteria” Antiphospholipid Antibodies

Anti-beta-2 glycoprotein I epitope specificity: from experimental models to diagnostic tools

Autoantibodies to domain 1 of beta 2 glycoprotein I determined using a novel chemiluminescence immunoassay demonstrate association with thrombosis in patients with antiphospholipid syndrome

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