High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura - Institut Pasteur Access content directly
Journal Articles The Journal of clinical investigation Year : 2022

High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura

Aurélien Sokal

Abstract

The major therapeutic goal for immune thrombocytopenia (ITP) is to restore normal platelet counts using drugs to promote platelet production or by interfering with mechanisms responsible for platelet destruction. 80% of patients possess anti-integrin αIIbβ3 (GPIIbIIIa) IgG autoantibodies causing platelet opsonization and phagocytosis. The spleen is considered the primary site of autoantibody production by autoreactive B cells and platelet destruction. The immediate failure in ~50% of patients to recover a normal platelet count after anti-CD20 Rituximab-mediated B cell depletion and splenectomy suggest that autoreactive, rituximab-resistant, IgG-secreting B cells (IgG-SC) reside in other anatomical compartments. We analyzed >3,300 single IgG-SC from spleen, bone marrow and/or blood of 27 patients with ITP revealing high inter-individual variability in affinity for GPIIbIIIa with variations over 3 logs. IgG-SC dissemination and range of affinities were however similar per patient. Longitudinal analysis of autoreactive IgG-SC upon treatment with anti-CD38 mAb daratumumab demonstrated variable outcomes, from complete remission to failure with persistence of high-affinity anti-GPIIbIIIa IgG-SC in the bone marrow. This study demonstrates the existence and dissemination of high-affinity autoreactive plasma cells in multiple anatomical compartments of patients with ITP that may cause the failure of current therapies.

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Immunology
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pasteur-03669881 , version 1 (17-05-2022)

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Pablo Canales-Herrerias, Etienne Crickx, Matteo Broketa, Aurélien Sokal, Guilhem Chenon, et al.. High-affinity autoreactive plasma cells disseminate through multiple organs in patients with immune thrombocytopenic purpura. The Journal of clinical investigation, 2022, ⟨10.1172/JCI153580⟩. ⟨pasteur-03669881⟩
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