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Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?

  • Diagnosis of Autoimmunity
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Abstract

Among the diagnostic assays for anti-phospholipid syndrome (APS), lupus anticoagulant (LA) is the strongest predictor of thrombosis; however, it presents several limitations as interference with anticoagulant therapy and poor inter-laboratory agreement. Two-thirds of LA activity is apparently due to antibodies against prothrombin (PT), usually detectable by ELISA. Binding of PT to phosphatidylserine (PS) has been shown to enhance solid-phase anti-PT assay sensitivity. To determine the prevalence of antibodies against PS/PT (aPS/PT) in APS, we tested the semiquantitative QUANTA Lite® aPS/PT ELISA in a cohort of 80 APS patients. The prevalence of aPS/PT was 81.3 %, rising to 87.6 % when considering LA-positive subjects only. We observed a strong correlation between aPS/PT and LA (p = 0.006). To note, APS patients with thrombotic manifestations displayed significantly higher IgG aPS/PT titers compared to 20 aPL asymptomatic carriers (p = 0.012). To rule out a possible cross-reactivity of anti-β2 glycoprotein I antibodies (aβ2GPI) with PS/PT complex, we tested two monoclonal aβ2GPI antibodies and an affinity-purified (AP) polyclonal aβ2GPI IgG obtained from the serum of a patient reacting against both β2GPI and PS/PT. The two monoclonal antibodies did not show any reactivity against PS/PT complex, similarly the AP IgGs did not react toward PS/PT antigen while preserved their aβ2GPI activity. Our findings suggest that aPS/PT are a definite antibody population in APS. Moreover, the good correlation between aPS/PT ELISA and LA may support its use as a surrogate test for LA, particularly useful to overcome the technical limitations of the functional assay.

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Conflict of interest

Susan Encabo, Zakera Shums, and Gary L. Norman are employees of INOVA Diagnostics, Inc.

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Authors and Affiliations

  1. Immunology Research Laboratory, IRCCS Istituto Auxologico Italiano, Via Zucchi 18, 20095, Cusano Milanino, Milan, Italy

    Francesca Pregnolato, Cecilia B. Chighizola, Maria Orietta Borghi & Pier Luigi Meroni

  2. Department of Clinical Sciences and Community Health, University of Milan, Via Festa del Perdono 7, 20122, Milan, Italy

    Cecilia B. Chighizola, Armando Tripodi, Veena Chantarangkul, Maria Orietta Borghi & Pier Luigi Meroni

  3. INOVA Diagnostics, Inc., 9900 Old Grove Road, San Diego, CA, 92131, USA

    Susan Encabo, Zakera Shums & Gary L. Norman

  4. Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, IRCCS Cà Granda Maggiore Hospital Foundation, Via Francesco Sforza, 35, 20122, Milan, Italy

    Armando Tripodi & Veena Chantarangkul

  5. Immunology and Allergology Unit, Ospedale Umberto I, Via Magellano 1, 10128, Turin, Italy

    Tiziana Bertero

  6. Haemostasis Unit, Department of Medicine, Azienda Ospedaliera Provincia di Lecco, Via dell’Eremo 9/11, 23900, Lecco, Italy

    Valeria De Micheli

  7. Division of Rheumatology, Istituto Ortopedico Gaetano Pini, Piazza A. Cardinal Ferrari 1, 20122, Milan, Italy

    Pier Luigi Meroni

Authors
  1. Francesca Pregnolato
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  2. Cecilia B. Chighizola
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  3. Susan Encabo
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  4. Zakera Shums
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  5. Gary L. Norman
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  8. Tiziana Bertero
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  9. Valeria De Micheli
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  10. Maria Orietta Borghi
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  11. Pier Luigi Meroni
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Correspondence to Pier Luigi Meroni.

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Pregnolato, F., Chighizola, C.B., Encabo, S. et al. Anti-phosphatidylserine/prothrombin antibodies: an additional diagnostic marker for APS?. Immunol Res 56, 432–438 (2013). https://doi.org/10.1007/s12026-013-8421-z

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  • DOI: https://doi.org/10.1007/s12026-013-8421-z

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