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Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up

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Abstract

Among patients with venous thromboembolism (VTE), the persistent detection of antiphospholipid (aPL) antibodies (Ab) represents an independent high risk factor for recurrence. However, oral anticoagulation vitamin K antagonist therapy, frequently used in these patients, is problematic in assessing and/or confirming a diagnosis of primary aPL syndrome (pAPS), suggesting use of alternative strategies. For this reason, and by analogy with other autoimmune diseases, a flow cytometer approach testing peripheral T cell subsets (CD3, CD4, and CD8), B cell subsets (B1, transitional, naive, and memory), and NK cells can be proposed. As an example and to validate the concept, pAPS patients selected from the monocentric VTE case–control EDITH’s cohort were selected during their follow-up. As suspected and in contrast to non-APS VTE patients, other autoimmune diseases, and controls, pAPS VTE patients displayed specific lymphocyte disturbances. Quantitative and qualitative modifications were related to total CD4+ T cell reduction, a lower CD4/CD8 ratio, and disturbance in B cell homeostasis with increased proportions of B1 cells, transitional B cells (CD24++CD38++), and naive B cells (IgD+CD27−), while memory B cells (IgD+CD27+ and IgD−CD27+) were reduced. Interestingly, the absolute number of CD4+ T cells positively correlated with IgG anti-cardiolipin Ab levels. Altogether, disturbances of T and B cell homeostasis characterized pAPS VTE patients during their follow-up. This suggests a means of profiling that could be used in addition to existing criteria to characterize them.

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Acknowledgments

We are grateful to Simone Forest and Geneviève Michel for their help in typing the paper and to Dr. Wesley H. Brooks (Tampa, USA) for editorial assistance.

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    Authors and Affiliations

    1. Laboratory of Immunology and Immunotherapy, Hôpital Morvan, University Hospital of Brest, Brest, France

      Laurent Simonin, Julie Lemerle, Boutahar Bendaoud, Sophie Hillion & Yves Renaudineau

    2. INSERM ESPRI, ERI29/EA2216, LabEx IGO “Immunotherapy Graft Oncology”, Réseau épigénétique et réseau canaux ioniques du Cancéropole Grand Ouest, European University of Brittany, Brest, France

      Laurent Simonin, Divi Cornec, Boutahar Bendaoud, Sophie Hillion, Jacques-Olivier Pers & Yves Renaudineau

    3. Department of Internal Medicine and Chest Diseases, European University of Brittany, EA3878 (G.E.T.B.O, Hôpital Cavale Blanche, University Hospital of Brest, Brest, France

      Laurent Simonin, Elisabeth Pasquier, Christophe Leroyer & Francis Couturaud

    4. Unit of Rheumatology, Hôpital Cavale Blanche, University Hospital of Brest, Brest, France

      Divi Cornec

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    1. Laurent Simonin
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    Francis Couturaud and Yves Renaudineau contributed equally to this work.

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    Simonin, L., Pasquier, E., Leroyer, C. et al. Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up. Clinic Rev Allerg Immunol 53, 14–27 (2017). https://doi.org/10.1007/s12016-016-8568-1

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