Recombinant anti-idiotypic antibodies inhibit human natural anti-glycoprotein (GP)IIb/IIIa autoantibodies
- Author(s)
- Escher, R; Vogel, M; Escher, G; Miescher, S; Stadler, BM; Berchtold, P;
- Details
- Publication Year 2002-02,Volume 18,Issue #1,Page 71-81
- Journal Title
- JOURNAL OF AUTOIMMUNITY
- Publication Type
- Journal Article
- Abstract
- Anti-idiotypic antibodies (anti-Id) have been described against idiotypes expressed on various autoantibodies. Since an immunoregulatory effect has been postulated for anti-Id, modulation of the anti-Id response in autoimmune disease may be of interest. In chronic immune thrombocytopenic purpura (AITP), autoantibodies directed mainly against platelet membrane glycoprotein (GP) IIb/IIIa cause platelet destruction by Fc-mediated phagocytosis or by complement lysis. We have previously reported on the generation of two recombinant anti-GPIIb/IIIa autoantibody fragments (PDG-X, PDG-B), that are specific for conformationally intact GPIIb/IIIa and inhibit binding of autoantibodies from patients with AITP. In the present study, we show that anti-GPIIb/IIIa specificities are not limited to a single individual by isolating five additional anti-GPIIb/IIIa autoantibody fragments from a second phagemid Fab library of an unrelated healthy donor. Using soluble Fab of PDG-X and PDG-B as antigens for panning Fab phagemid libraries from healthy human individuals, we isolated anti-Id phage clones specific for PDG-X or PDG-B. In addition they inhibited the binding of PDG-X or PDG-B to GPIIb/IIIa. Amino acid sequence comparison between these specific anti-Id and GPIIb/IIIa was performed. Generation of these anti-Id directed against pathologically relevant anti-GPIIb/IIIa autoantibodies may represent a new suitable and specific therapeutic option for the treatment of antibody-mediated AITP. (C) 2002 Elsevier Science Ltd.
- Publisher
- ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD
- Keywords
- IMMUNE THROMBOCYTOPENIC PURPURA; ANTIIDIOTYPIC ANTIBODY; SYSTEMIC VASCULITIS; CLONAL SELECTION; PHAGE DISPLAY; GENE USAGE; SEQUENCE; BINDING; REPERTOIRE; NETWORK
- Publisher's Version
- https://doi.org/10.1006/jaut.2001.0560
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2002-02-01 12:00:00