HUMAN BALB RADIATION CHIMERA ENGRAFTED WITH SPLENOCYTES FROM PATIENTSWITH IDIOPATHIC THROMBOCYTOPENIC PURPURA PRODUCE HUMAN PLATELET ANTIBODIES/

We have previously shown that lethally irradiated normal strains of mi ce, radioprotected with severe combined immunodeficient (SCID) bone ma rrow, 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. I n the present study, we adoptively transferred splenocytes from patien ts with chronic immune thrombocytopenic purpura (ITP) into lethally ir radiated BALB/c mice, radioprotected with SCID bone marrow. High titre s of total human immunoglobulin appeared as early as 2 weeks post-tran splant and declined after 6 weeks, while human anti-human platelet ant ibodies were detected 2-8 weeks after the transfer of splenocytes. The immunoglobulin G (IgG) fraction contained antibodies against glycopro tein (GP) IIb/IIIa (CD41) or GPIb/IX (CD42). The human platelet antibo dies showed a low level of cross-reactivity with mouse platelets, and thrombocytopenia in the animals was not observed. Splenocytes from ind ividual ITP patients differed in their capacity to produce either huma n platelet antibodies or total human immunoglobulin. Furthermore, anti bodies 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 the rapeutics in ITP.