Author/Editor		George, Jacob; Blank, Miri; Gilburd, Boris; Hojnik, Maya; Shenkman, Boris; Tamarin, Ilia; Varon, David; Matsuura, Eiji; Koike, Takao; Shoenfeld, Yehuda
Title		Immunologic characterization and functional properties of murine antibodies raised against deleted mutants of human beta2-glycoprotein I
Type		članek
Source		Int Immunol
Vol. and No.		Letnik 9, št. 6
Publication year		1997
Volume		str. 913-21
Language		eng
Abstract		Beta2-Glycoprotein I (beta2GPI) is a 50 kDa molecule proposed as a principal target of "autoimmune" antiphospholipid antibodies (aPL). We have used deleted mutants (DM) representing different domains of beta2GPI (I-IV, IV-V and V) for immunization of naive mice and studied the characteristics of the respective murine IgG preparations in comparison with affinity-purfied IgG from two patients with primary antiphospholipid syndrome. Immunization with beta2GPI and with DM produced anti-beta2GPI antibodies, part of which reacted with negatively charged phospholipids (PL), whereas reactivity with cardiolipin was evident only in the IgG from mice immunized with beta2GPI. These results are consistent with the presumption that aPL are induced following the in vivo association of beta2GPI (used for immunization) with resident negatively charged PL. Accordingly, DM which either lack the PL binding site or aPL attachment locus did not elicit, upon immunization, antibodies reactive with PL. Further, murine anti beta2GPI IgG and human "autoimmune" aPL were similar, albeit not identical, in terms of DM requirement for PL binding and charge dependency. Murine antibodies and human aPL, regardless of their binding characteristics, were found to bind significantly to platelets upon their activation with thrombin and to promote platelet activation. The results of the current study emphasize the dissimilarities between human "autoimmune" aPL and murine anti-beta2GPI. Thus, anti-beta2GPI antibodies to different DM as well as human aPL are capable of binding and activating human platelets provided beta2GPI is present.
Descriptors		ANTIPHOSPHOLIPID SYNDROME ANTIBODIES, ANTIPHOSPHOLIPID GLYCOPROTEINS BLOOD PLATELETS IGG MICE BINDING SITES, ANTIBODY BINDING, COMPETITIVE MUTAGENESIS PLATELET ACTIVATION P-SELECTIN SEQUENCE DELETION THROMBIN