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Recombinant human natural autoantibodies against GPIIb/IIIa inhibit binding of autoantibodies from patients with AITP
- Source :
- British Journal of Haematology. 102:820-828
- Publication Year :
- 1998
- Publisher :
- Wiley, 1998.
-
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.
- Subjects :
- congenital, hereditary, and neonatal diseases and abnormalities
Phage display
Autoantibody
Hematology
Biology
Molecular biology
Epitope
law.invention
Antigen
law
hemic and lymphatic diseases
Immunology
Monoclonal
Recombinant DNA
biology.protein
Platelet
Antibody
circulatory and respiratory physiology
Subjects
Details
- ISSN :
- 00071048
- Volume :
- 102
- Database :
- OpenAIRE
- Journal :
- British Journal of Haematology
- Accession number :
- edsair.doi...........cab8cbdd74b91b8ae4652a9c08de0435