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Hoemberg, M; Stahl, D; Schlenke, P; Sibrowski, W; Pachmann, U; Cassens, U.
The isotype of autoantibodies influences the phagocytosis of antibody-coated platelets in autoimmune thrombocytopenic purpura.
Scand J Immunol. 2011; 74(5): 489-495. Doi: 10.1111/j.1365-3083.2011.02600.x [OPEN ACCESS]
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Co-authors Med Uni Graz
Schlenke Peter
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Abstract:
Autoimmune thrombocytopenic purpura (AITP) is an acquired autoimmune bleeding disorder, characterized by isolated thrombocytopenia because of destruction of auto-antibody-coated platelets by Fc-receptor-mediated phagocytosis. The destruction of autoantibody-sensitized platelets by FcγR-bearing phagocytic cells and the following antigen presentation are considered to play a key role for the pathophysiology of AITP. Although different isotypes of AITP-mediating autoantibodies, e.g. IgG, IgM and IgA, are frequently found in AITP patients, their role in the pathophysiology of AITP remains unclear. Using a flow cytometric monocyte-based phagocytosis assay, we investigated the impact of disease-associated autoantibody isotype in antibody-mediated phagocytosis of platelets. Platelets, labelled with 5-chloromethyl fluorescein diacetate (CMFDA), were incubated with AITP patients' serum characterized by pure IgG or IgM antiplatelet autoantibodies. Labelled platelets were incubated with monocytes. Phagocytosis was defined as the product of percentage of CMFDA-positive monocytes and mean fluorescence intensity of CMFDA. Adherence of platelets to monocytes was quantified by anti-CD61-PerCp in a CMFDA(+) CD14(+) gate. IgG-coated platelets showed a significantly higher phagocytic index than IgM-coated platelets (mean 796 ± 157 versus 539 ± 78, P < 0.01). There were no significant differences regarding platelet adherence to monocytes. The isotype of autoantibodies influences the quantity of in vitro phagocytosis of autologous platelets by monocytes. Therefore, the AITP-mediating autoantibody isotype should be considered more carefully in pathophysiologic models and furthermore in diagnostic, therapeutic and prognostic approaches in AITP.
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Adult -
Antigens, CD14 - biosynthesis
Autoantibodies - chemistry Autoantibodies - metabolism Autoantibodies - pharmacology
Blood Platelets - drug effects Blood Platelets - immunology Blood Platelets - metabolism Blood Platelets - pathology
Cell Separation -
Flow Cytometry -
Humans -
Immune Sera - metabolism Immune Sera - pharmacology
Immunoglobulin G - chemistry Immunoglobulin G - metabolism Immunoglobulin G - pharmacology
Immunoglobulin M - chemistry Immunoglobulin M - metabolism Immunoglobulin M - pharmacology
Integrin beta3 - biosynthesis
Monocytes - immunology Monocytes - metabolism Monocytes - pathology
Phagocytosis - drug effects
Platelet Adhesiveness - drug effects
Purpura, Thrombocytopenic, Idiopathic - blood Purpura, Thrombocytopenic, Idiopathic - diagnosis Purpura, Thrombocytopenic, Idiopathic - immunology
Receptors, IgG - immunology Receptors, IgG - metabolism
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