Platelet Membrane Glycoprotein IIb/IIIa has Sequence Homologies with Human Virus Proteins and Synthetic Viral Peptides Inhibit Anti-GPIIb/IIIa Antibodies in Autoimmune Thrombocytopenic Purpura

Human platelet GP IIb/IIIa and common human viruses showed sequence homologies of up to 220 amino acids. High scoring homologies were found in Herpes Simplex, Varicella Zoster, Epstein-Barr virus, Adenovirus and Cytomegalovirus, all of which cause lifelong latent infections. Further high scoring sequences were found in Measles, Mumps and Rubella, which are sporadically associated with acute autoimmune thrombocytopenic purpura (AITP). Lower scoring homologies were found in Parvovirus, coxsackie B and Human Immunodeficiency Virus. There were frequent homologies to known autoantibody-binding epitopes in the cysteine-rich and intracytoplasmic regions of GP IIb/IIIa, but also with the RGD-binding and calcium-binding regions, and with the nascent GP signal peptide which is not expressed in the functional glycoprotein. Peptides representing the 48 highest scoring viral sequences were synthesised in vitro, and 7 of these viral peptides were shown to inhibit the serum autoantibodies of adults with chronic AITP. The pattern and degree of autoantibody inhibition varied from patient to patient, was concentration dependent and distinct for each peptide. This suggests that polyclonal GP IIb/IIIa autoantibodies are directed to different GP epitopes and are cross reactive in different patients to different viral proteins in different viruses. The results suggest that human viruses have a role in the aetiology of AITP via molecular mimicry of platelet GP IIb/IIIa, and that chronic auto immunity may be related to a persistent antigenic stimulus from lifelong latent viral infections.