Recombinant anti-idiotypic antibodies inhibit human natural anti-glycoprotein (GP)IIb/IIIa autoantibodies.
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 antiId 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.
Escher
R
R
Central Hematology Laboratory, University Hospital, Bern, Switzerland. escher@wehi.edu.au
Vogel
M
M
Escher
G
G
Miescher
S
S
Stadler
B M
BM
Berchtold
P
P
D000595:Amino Acid Sequence; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism* / Q000627:therapeutic use; D000915:Antibody Affinity / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology; D001323:Autoantibodies / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000276:immunology; D001667:Binding, Competitive / Q000276:immunology; D003001:Cloning, Molecular; D018604:Epitope Mapping / Q000379:methods; D006801:Humans; D007128:Immunoglobulin Fragments / Q000627:therapeutic use; D007167:Immunotherapy; D008969:Molecular Sequence Data; D019151:Peptide Library; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000276:immunology / Q000628:therapy; D011994:Recombinant Proteins / Q000378:metabolism* / Q000627:therapeutic use
D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D007128:Immunoglobulin Fragments; D019151:Peptide Library; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011994:Recombinant Proteins