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 ho mologies of up to 220 amino acids. High scoring homologies were found in Herpes Simplex, Varicella Zoster, Epstein-Barr virus, Adenovirus an d Cytomegalovirus, ah of which cause lifelong latent infections. Furth er high scoring sequences were found in Measles, Mumps and Rubella, wh ich are sporadically associated with acute autoimmune thrombocytopenic purpura (AITP), Lower scoring homologies were found in Parvovirus, co xsackie B and Human Immunodeficiency Virus. There were frequent homolo gies to known autoantibody-binding epitopes in the cysteine-rich and i ntracytoplasmic regions of GP IIb/IIIa, but also with the RGD-binding and calcium-binding regions, arid with the nascent GP signal peptide w hich is not expressed in the functional glycoprotein. Peptides represe nting the 48 highest scoring viral sequences were synthesised in vitro , and 7 of these viral peptides were shown to inhibit the serum autoan tibodies of adults with chronic AITP. The pattern and degree of autoan tibody inhibition varied from patient to patient, was concentration de pendent and distinct for each peptide. This suggests that polyclonal G P IIb/IIIa autoantibodies are directed to different GP epitopes and ar e 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 antige nic stimulus from lifelong latent viral infections.