Human/BALB radiation chimera engrafted with splenocytes from patients with idiopathic thrombocytopenic purpura produce human platelet antibodies

Abstract

SUMMARYWe have previously shown that lethally irradiated normal strains of mice, radioprotected with severe combined immunodeficient (SCID) bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC ). The human/mouse radiation chimera can mount marked humoral and cellular responses to recall antigens, as well as primary responses. In the present study, we adoptively transferred splenocytes from patients with chronic immune thrombocytopenic purpura (ITP) into lethally irradiated BALB/c mice, radioprotected with SCID bone marrow. High titres of total human immunoglobulin appeared as early as 2 weeks post-transplant and declined after 6 weeks, while human anti-human platelet antibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycoprotein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibodies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from individual ITP patients differed in their capacity to produce either human platelet antibodies or total human immunoglobulin. Furthermore, antibodies produced in the murine system were not always identical to the original antibodies present in the serum of the patients. The study of the serological aspects of autoantibodies against human platelets in an animal model might be useful for the investigation of potential therapeutics in ITP.

A Role of Autoantibody–Mediated Platelet Destruction in Thrombocytopenia in Patients With Cirrhosis

“…To further verify the pathogenic role of anti-GPIIb-IIIa antibodies, it is necessary to test whether thrombocytopenia can be induced by injecting anti-GPIIb-IIIa antibodies derived from patients with LC into animals, although anti-GPIIb-IIIa antibodies from patients with ITP have been shown to have a low level of cross-reactivity with mouse platelets. 40 The anti-GPIIb-IIIa antibody response was detected in patients with LC independent of the etiology, indicating that platelet-specific autoantibody production is asso-ciated with a pathogenic process shared by diverse etiologies of LC. Our previous studies on patients with ITP showed that the spleen is a primary site for both anti-platelet antibody production and platelet destruction.…”

Recognition of highly restricted regions in the β-propeller domain of αIIb by platelet-associated anti-αIIbβ3 autoantibodies in primary immune thrombocytopenia

“…However, one report suggested that anti-human platelet Abs produced from splenocytes obtained from patients with ITP exhibited low crossreactivity with mouse platelets. 24 Another report showed that an anti-human ␣IIb antibody generated in mice exhibited significantly diminished binding to ITP platelets compared with normal platelets. 25 Those results suggested that the reactivity of PA anti-␣IIb␤3 Abs may be affected by subtle conformational differences between human and mouse ␣IIb␤3.…”

A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy

“…Thus, an animal model is important to study the pathogenesis of FNAITP and to monitor potential therapeutic effects. While several models of other immune thrombocytopenia have been reported, [17][18][19] no previous animal model of FNAITP exists.…”