Reliability of Lupus Anticoagulant and Anti-phosphatidylserine/prothrombin Autoantibodies in Antiphospholipid Syndrome: A Multicenter Study

Sciascia, Savino; Radin, Massimo; Cecchi, Irene; Rubini, Elena; Scotta, Anna; Rolla, Roberta; Montaruli, Barbara; Pergolini, Patrizia; Mengozzi, Giulio; Muccini, Emanuela; Baldovino, Simone; Ferro, Michela; Vaccarino, A; Mähler, Michael; Menegatti, Elisa; Roccatello, Dario

doi:10.3389/fimmu.2019.00376

Cited by 40 publications

(36 citation statements)

References 32 publications

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“…This approach is particularly important when it comes to the identification of a novel biomarker to diagnose seronegative APS patients. 24,56,57 A final comment goes to the potential clinical significance of our findings. Because of their different mechanism of prothrombin binding, type I and II Abs might have different origin and pathologic effects.…”

Section: Discussionmentioning

confidence: 90%

Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis

et al. 2019

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Anti-phosphatidylserine/prothrombin (aPS/PT) antibodies are often detected in patients with antiphospholipid syndrome (APS), but how aPS/PT engage prothrombin at the molecular level remains unknown. Here, the antigenic determinants of immunoglobulin G aPS/PT were investigated in 24 triple-positive APS patients at high risk of thrombosis by using prothrombin mutants biochemically trapped in closed and open conformations, and relevant fragments spanning the entire length of prothrombin. Two novel unexpected findings emerged from these studies. First, we discovered that some aPS/PT are unique among other anti-prothrombin antibodies insofar as they efficiently recognize prothrombin in solution after a conformational change requiring exposure of fragment-1 to the solvent. Second, we identified and characterized 2 previously unknown subpopulations of aPS/PT, namely type I and type II, which engage fragment-1 of prothrombin at different epitopes and with different mechanisms. Type I target a discontinuous density-dependent epitope, whereas type II engage the C-terminal portion of the Gla-domain, which remains available for binding even when prothrombin is bound to the phospholipids. Based on these findings, APS patients positive for aPS/PT were classified into 2 groups, group A and group B, according to their autoantibody profile. Group A contains mostly type I antibodies whereas group B contains both type I and type II antibodies. In conclusion, this study offers a first encouraging step toward unveiling the heterogeneity of anti-prothrombin antibodies in correlation with thrombosis, shedding new light on the mechanisms of antigen–autoantibody recognition in APS.

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Section: Discussionmentioning

confidence: 90%

Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis

et al. 2019

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“…Anti-phosphatidylserine/prothrombin antibodies (aPS/ PT) are now acknowledged as a highly effective potential marker for APS [10,11]. As a result of its remarkable diagnostic performance and high prevalence in the LA-positive patient group, as validated by multiple studies [12][13][14], aPS/PT has gained much attention and was included in both the APS-S (Otomo) and the Global APS Score (GAPSS), widely used systems for patient thrombotic risk assessment [15]. Additional biomarkers continue to be evaluated for their value to APS diagnosis and management.…”

Section: Introductionmentioning

confidence: 99%

“Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort

Liu

Wan

et al. 2020

Arthritis Res Ther

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Background: Despite expansion in the 2006 Sydney antiphospholipid syndrome (APS) classification criteria to include IgG/IgM anti-β2-glycoprotein (aβ2GPI) antibodies in addition to IgG/IgM anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LAC), some individuals with clinical features of APS remain seronegative (seronegative APS or SNAPS) and are at risk of recurrent thrombosis and pregnancy morbidities. Our aim was to assess the value of "non-criteria" aPL antibodies to detect these SNAPS patients.Methods: One hundred ninety-two APS patients, 90 SNAPS patients, 193 autoimmune disease controls, and 120 healthy controls were evaluated. Ten antiphospholipid antibodies (aPLs) were tested using commercial kits, including 5 non-criteria aPLs: anti-phosphatidylserine/prothrombin antibodies (aPS/PT) IgG/IgM, aCL IgA, aβ2GPI IgA, and anti-β2GPI Domain 1 (aβ2GPI-D1) IgG. Results: Up to 60.9% of the SNAPS and 93.5% of APS patients were detected by at least one non-criteria aPL. aPS/ PT IgG had the highest Youden index in classifying APS and SNAPS from controls. aPS/PT IgG and aβ2GPI Domain 1 IgG seem to be the most significant risk factors for thrombotic events and pregnancy morbidity, respectively. aPS/ PT IgG/IgM and aβ2GPI-D1 IgG were detected in some SNAPS patients, while IgA isotypes of aCL/aβ2GPI tended to appear together with other biomarkers. The combined analysis showed enhanced diagnostic performance with the inclusion of non-criteria aPLs. Conclusions: Recognition of SNAPS patients is critical for clinical management and prevention of potential thrombotic and obstetric adverse events. The non-criteria antiphospholipid antibodies help to identify a considerable portion (60.9%) of these patients who otherwise may remain untreated and at clinical risk.

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“…Furthermore, although several studies have suggested that testing for "extra criteria" aPL specificities may help to identify patients at higher risk for developing clinical manifestations of the syndrome, their role in LO-PC needs further investigation. 9,10 In particular, IgA isotypes, phosphatidylserine-prothrombin antibodies (aPS/PT) and β2GPI-Domain 1 (β2GPI-D1) have been proposed to be particularly relevant in the antiphospholipid syndrome setting, but their relevance in the specific context of pregnancy needs to be confirmed. [11][12][13] Our study aimed to investigate the prevalence of aPL antibodies, both "criteria" and "extra criteria," in a cohort of women who experienced LO-PC with low risk for chromosomal abnormalities.…”

Section: Introductionmentioning

confidence: 99%

The prevalence of antiphospholipid antibodies in women with late pregnancy complications and low‐risk for chromosomal abnormalities

Foddai

Radin

Cecchi

et al. 2020

Journal of Thrombosis and Haemostasis

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Background: Antiphospholipid antibodies (aPL) are known to increase the risk of obstetrical complications. However, aPL significance and prevalence in women with late-onset pregnancy complications (LO-PC) need further clarification. Objectives: To investigate the prevalence of aPL in a cohort of women who experienced LO-PC and to compare it with a cohort of uneventful pregnancies. Methods: One hundred pregnant women who experienced LO-PC, had a low risk for chromosomal abnormalities, and absence of fetal abnormalities were recruited from August 2018 to August 2019. One hundred women with uneventful pregnancy were included as controls. aPL testing was performed on serum samples derived from prenatal screening test and included both criteria and "extra criteria" aPL. Results: Patients with LO-PC had significantly higher aPL prevalence when compared with controls (31/100 [31%] vs 10/100 [10%]; P < .001). More in detail, up to 26% of women with LO-PC were positive for one aPL, with an overall prevalence significantly higher than controls (26% vs 9%; P < .05). Among single aPL positivity, patients had significantly higher rate of positivity and titers of anticardiolipin IgG (10% vs 2%; mean ± standard deviation 11 ± 13 vs 4 ± 9.6 chemoluminescent unit; P < .05) and phosphatidylserine-prothrombin antibodies (aPS/PT) IgM (15% vs 6%; mean ± standard deviation 10.2 ± 21.7 vs 3.7 ± 13.7 U; P < .05). Testing for aPS/PT (IgM/IgG) alone allowed the identification of 17 patients negative for criteria aPL. aPL-positive patients had a significantly higher risk of preterm birth (34-36 + 6 weeks; 10% vs 8%; P < .012). Conclusions: We report a high prevalence of aPL in our cohort. Testing for both criteria and "extra criteria" aPL in women with previous LO-PC could improve the diagnostic accuracy identifying women at higher risk for recurrent pregnancy complications.

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Reliability of Lupus Anticoagulant and Anti-phosphatidylserine/prothrombin Autoantibodies in Antiphospholipid Syndrome: A Multicenter Study

Cited by 40 publications

References 32 publications

Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis

Discovery and characterization of 2 novel subpopulations of aPS/PT antibodies in patients at high risk of thrombosis

“Non-criteria” antiphospholipid antibodies add value to antiphospholipid syndrome diagnoses in a large Chinese cohort

The prevalence of antiphospholipid antibodies in women with late pregnancy complications and low‐risk for chromosomal abnormalities

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