Journalartikel

Jahr der Veröffentlichung: 2023

Seiten: 3561-3572

Zeitschrift: Blood Advances

Bandnummer: 7

Heftnummer: 14

ISSN: 2473-9529

eISSN: 2473-9537

Open Access Status: Gold

DOI Link: https://doi.org/10.1182/bloodadvances.2022009423

Verlag: American Society of Hematology (ASH Publications)

Abstract: 
Humoral antiplatelet factors, such as autoantibodies, are thought to primarily clear platelets by triggering macrophage phagocytosis in immune thrombocytopenia (ITP). However, there are few studies characterizing the capacity and mechanisms of humoral factor-triggered macrophage phagocytosis of platelets using specimens from patients with ITP. Here, we assessed sera from a cohort of 24 patients with ITP for the capacity to trigger macrophage phagocytosis of normal donor platelets and characterized the contribution of humoral factors to phagocytosis. Sera that produced a phagocytosis magnitude greater than a normal human serum mean + 2 standard deviations were considered phagocytosispositive. Overall, 42% (8/19) of MHC I alloantibody-negative ITP sera were phagocytosispositive. The indirect monoclonal antibody immobilization of platelet antigens assay was used to detect immunoglobulin G (IgG) autoantibodies to glycoproteins (GP)IIb/IIIa, GPIb/ IX, and GPIa/IIa. Autoantibody-positive sera triggered a higher mean magnitude of phagocytosis than autoantibody-negative sera. Phagocytosis correlated inversely with platelet counts among autoantibody-positive patients but not among autoantibodynegative patients. Select phagocytosis-positive sera were separated into IgG-purified and -depleted fractions via protein G and reassessed for phagocytosis. Phagocytosis was largely retained in the purified IgG fractions. In addition, we assessed serum concentrations of C-reactive protein, serum amyloid P, and pentraxin 3 as potential phagocytosis modulators. Pentraxin 3 concentrations correlated inversely with platelet counts among patients positive for autoantibodies. Taken together, sera from approximately half of the patients with ITP studied triggered macrophage phagocytosis of platelets beyond a normal level. An important role for antiplatelet autoantibodies in phagocytosis is supported; a role for pentraxins such as pentraxin 3 may be suggested.

Harvard-Zitierstil: Norris, P., Tawhidi, Z., Sachs, U., Cserti-Gazdewich, C., Lin, Y., Callum, J., et al. (2023) Serum from half of patients with immune thrombocytopenia trigger macrophage phagocytosis of platelets, Blood Advances, 7(14), pp. 3561-3572. https://doi.org/10.1182/bloodadvances.2022009423

APA-Zitierstil: Norris, P., Tawhidi, Z., Sachs, U., Cserti-Gazdewich, C., Lin, Y., Callum, J., Gonzalez, L., Shan, Y., Branch, D., & Lazarus, A. (2023). Serum from half of patients with immune thrombocytopenia trigger macrophage phagocytosis of platelets. Blood Advances. 7(14), 3561-3572. https://doi.org/10.1182/bloodadvances.2022009423