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Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements

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Abstract

The international classification criteria for definite antiphospholipid syndrome (APS) include three laboratory measurements: lupus anticoagulant (LA), IgG and IgM isotypes of anti-cardiolipin (aCL) and anti-β2glycoprotein I antibodies (anti-β2GPI). When persistently elevated, they are specific for APS; however, many patients that fulfil clinical criteria may exhibit negative serological results. These “seronegative” APS (SN-APS) are exposed to an increased thrombotic risk. The aims of our cross-sectional, retrospective study of consecutive autoimmune patients’ samples were to evaluate the association of non-criteria antiphospholipid antibodies (aPL) with thrombosis and obstetric events, to calculate the risk score for adverse events and to assess the specific contribution of single aPL positivity in SN-APS. LA, aCL, anti-β2GPI and anti-phosphatidylserine/prothrombin antibodies (aPS/PT) of IgG, IgM, and IgA isotypes were determined in sera of 323 patients with autoimmune disorders. Medical records of all patients were carefully analyzed. aCL, anti-β2GPI and aPS/PT of IgG and IgA isotypes were significantly associated with thrombosis while none of the IgM aPL showed such association. aPS/PT of all isotypes, aCL and anti-β2GPI of IgG and IgA isotype showed significant correlation to obstetric events. When considering results of aPS/PT ELISA, we could additionally identify 3% of thrombotic patients and 2% of obstetric patients. Thrombotic and obstetric risk scores were calculated showing significantly higher association to clinical events, as compared to evaluating individual risk factors. aPS/PT could represent an additional biomarker in SN-APS patients. IgA aPL are associated with thrombosis and obstetric complications. Risk scores accounting different aPL and conventional risk factors, better assesses risk for adverse event, as compared to evaluating individual factors alone.

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Authors and Affiliations

  1. Department of Rheumatology, Immunology Laboratory, University Medical Centre Ljubljana, SI-1000, Ljubljana, Slovenia

    Polona Žigon, Anuška Podovšovnik, Aleš Ambrožič, Matija Tomšič, Alojzija Hočevar, Nataša Gašperšič, Žiga Rotar, Sonja Praprotnik, Snežna Sodin Šemrl & Saša Čučnik

  2. Faculty of Medicine, University of Ljubljana, SI-1000, Ljubljana, Slovenia

    Matija Tomšič

  3. Faculty of Mathematics, Natural Sciences and Information Technologies, University of Primorska, SI-6000, Koper, Slovenia

    Snežna Sodin Šemrl

  4. Faculty of Pharmacy, Chair of Clinical Biochemistry, University of Ljubljana, SI-1000, Ljubljana, Slovenia

    Saša Čučnik

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  1. Polona Žigon
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  2. Anuška Podovšovnik
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  8. Sonja Praprotnik
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  9. Snežna Sodin Šemrl
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  10. Saša Čučnik
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Correspondence to Polona Žigon.

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The study was approved by the National Medical Ethics Committee, Ljubljana, Slovenia (#99/04/15), and all patients provided informed consent. We confirm that all experiments were performed in accordance with relevant guidelines and regulations.

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Rheumatology in Slovenia: Clinical practice and translational research

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Žigon, P., Podovšovnik, A., Ambrožič, A. et al. Added value of non-criteria antiphospholipid antibodies for antiphospholipid syndrome: lessons learned from year-long routine measurements. Clin Rheumatol 38, 371–378 (2019). https://doi.org/10.1007/s10067-018-4251-7

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