The Isotype of Autoantibodies Influences the Phagocytosis of Antibody‐Coated Platelets in Autoimmune Thrombocytopenic Purpura

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.

Diagnostic and Predictive Contribution of Autoantibodies Screening in a Large Series of Patients With Primary Immunodeficiencies

“…Such responses are likely to be triggered by infections, and molecular mimicry may play a central role in the development of self-directed anti-platelet immunity ( 17 , 18 ). Furthermore, a pathophysiological role of IgM anti-platelet antibodies in ITP has been demonstrated ( 16 , 19 ). Unlike IgM anti-erythrocyte autoantibody that promotes anemia through a massive agglutination of RBCs in spleen and liver, PA-IgM induces thrombocytopenia through uptake of opsonized platelets ( 19 , 20 ).…”

“…Furthermore, a pathophysiological role of IgM anti-platelet antibodies in ITP has been demonstrated ( 16 , 19 ). Unlike IgM anti-erythrocyte autoantibody that promotes anemia through a massive agglutination of RBCs in spleen and liver, PA-IgM induces thrombocytopenia through uptake of opsonized platelets ( 19 , 20 ). In the mouse, it has been reported that IgM autoantibody-mediated thrombocytopenia was macrophage dependent and the Fcα/μR was required for macrophage uptake of opsonized thrombocytes ( 21 ).…”

The Role of T cell Immunoglobulin and Mucin Domain‐3 in Immune Thrombocytopenia

“…However, the pathogenic mechanisms of ITP have not been clearly elucidated. The disease is classically characterized by autoantibodies opsonizing platelets and inducing premature destruction within the spleen . The underlying stimulator of autoimmunity is not known, but T cell dysregulation is considered to be responsible for the stimulus.…”

Trombocitopenia inmune. Guía de diagnóstico y tratamiento

“…Los avances que se han realizado e n l o s ú l t i m o s a ñ o s e n l a investigación de los mecanismos fisiopatogénicos involucrados han llevado a una comprensión mucho mejor de la enfermedad. [2][3][4][5][6][7][8][9][10] En la actualidad, es válido considerar la PTI como un síndrome, en el cual hay distintos mecanismos causales en los diversos individuos, que d e t e r m i n a n l a h e t e r o g e n e i d a d de sus manifestaciones clínicas y l a s d i f e r e n t e s r e s p u e s t a s a l o s tratamientos disponibles, y que ocurre dentro de contextos genéticos determinados. Las alteraciones d e l s i s t e m a i n m u n o l ó g i c o s o n múltiples.…”