Recombinant human natural autoantibodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP
Escher,
Müller,
Vogel,
Miescher,
Stadler,
Berchtold,
Escher
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this authorMüller
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this authorVogel
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorMiescher
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorStadler
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorBerchtold
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this author Escher,
Müller,
Vogel,
Miescher,
Stadler,
Berchtold,
Escher
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this authorMüller
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this authorVogel
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorMiescher
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorStadler
Institute of Immunology and Allergology, University Hospital, Bern, Switzerland
Search for more papers by this authorBerchtold
Department of Medicine, University Hospital, Bern, Switzerland,
Search for more papers by this authorDr Peter Berchtold Department of Medicine, University Hospital, Inselspital, CH-3010 Bern, Switzerland.
Abstract
Autoimmune thrombocytopenic purpura (AITP) is caused by autoantibodies predominantly against platelet membrane glycoproteins (GP) IIb/IIIa and GPIb/IX. Naturally occurring autoantibodies have been described against a variety of autoantigens; it has been suggested that perturbation of their regulation may be associated with autoimmune diseases. Using a combinatorial Fab phagemid library from an individual immunized with human RhD+ red blood cells, we evaluated the presence of natural anti-GPIIb/IIIa autoantibodies as well as their relation to AITP-associated anti-GPIIb/IIIa autoantibodies. Selection on native GPIIb/IIIa and characterization of positive clones by inhibition studies against murine monoclonal anti-GPIIb/IIIa antibodies and by DNA analysis revealed the presence of two distinct recombinant anti-GPIIb/IIIa autoantibodies, which partially inhibited binding of affinity-purified platelet-associated autoantibodies from 8/12 AITP patients. Our results demonstrated that GPIIb/IIIa-specific Fab directed against conformational epitopes within the GPIIb/IIIa complex may be cloned from the genome of an individual immunized with RhD+ red blood cells, who was not affected by AITP. The partial inhibition of binding of platelet-associated autoantibodies from AITP patients to GPIIb/IIIa by the recombinant anti-GPIIb/IIIa phage clones suggests recognition of closely related antigenic epitopes. These phage clones may represent down-regulated, potentially pathological autoantibodies and could be used as new tools for investigation of AITP.
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