Blood July 15; 106(2): 572–576. Role of molecular mimicry to HIV-1 peptides in HIV-1–related immunologic thrombocytopenia Zongdong Li, Michael A. Nardi, and Simon Karpatkin (…) Patients with early HIV-1 infection commonly develop an immunologic thrombocytopenia (HIV-1-ITP) 1 with shortened platelet survival. 2 Early onset HIV-1-ITP is clinically indistinguishable from classic autoimmune idiopathic thrombocytopenia (AITP) and responsive to the same therapeutic agents used to treat AITP. 1,3-6 However, HIV-1-ITP is different from AITP with respect to markedly elevated platelet-associated IgG, IgM, C 3, and C 4 and the presence of serum circulating immune complexes (CICs) composed of the same. 3,4 These CICs also contain specific high-affinity IgG1 antibody (Ab) against the platelet glycoprotein IIIa (GPIIIa) integrin, 7 its anti-idiotype blocking Ab, 8 and platelet fragments. 9 Unlike classic AITP in which multiple Abs have been described with different specificities for platelet GPIIb, GPIIIa, and GPIb, 6 patients with HIV-1-ITP have an IgG1 Ab against an immunodominant epitope, GPIIIa49-66 (CAPESIEFPVSEAREVLED). This Ab induces thrombocytopenia in mice (mouse GPIIIa has 83% sequence similarity with human GPIIIa and macrophages with Fc receptors capable of clearing human IgG1) and correlates inversely with platelet count in HIV-1-ITP patients (r =–0.71). 7, Morris L, Distenfeld A, Amorosi E, Karpatkin S. Autoimmune thrombocytopenic purpura in homosexual men. Ann Intern Med. 1982;96: []. 2. Najean Y, Rain JD. The mechanism of thrombocytopenia in patients with HIV infection. J Lab Clin Med. 1994;123: []. 3. Walsh C, Nardi M, Karpatkin S. On the mechanism of thrombocytopenic purpura in sexually-active homosexual men. N Engl J Med. 1984;311: []. 4. Savona S, Nardi M, Karpatkin S. Thrombocytopenic purpura in narcotics addicts. Ann Intern Med. 1985;102: []. 5. Ratnoff O, Menitove J, Aster R, Lederman M. Coincident classic hemophilia and “idiopathic” thrombocytopenic purpura in patients under treatment with concentrates of anti-hemophilic factor (factor VIII). N Engl J Med. 1983;308: []. 6. Karpatkin S. Autoimmune (idiopathic) thrombocytopenic purpura. Lancet. 1997;349: []. 7. Karpatkin S, Nardi M, Hymes K. Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor-immune complexes of human immunodeficiency virus 1 thrombocytopenic patients. Proc Natl Acad Sci U S A. 1995;92: []. 8. Nardi M, Karpatkin S. Antiidiotype antibody against platelet anti-GPIIIa contributes to the regulation of thrombocytopenia in HIV-1-ITP patients. J Exp Med. 2000;191: []. 9. Nardi M, Tomlinson S, Greco M, Karpatkin S. Complement-independent, peroxide induced antibody lysis of platelets in HIV-1-related immune thrombocytopenia. Cell. 2001;106: []. 10. Nardi MA, Liu LX, Karpatkin S. GPIIIa-(49-66) is a major pathophysiologically relevant antigenic determinant for anti-platelet GPIIIa of HIV-1-related immunologic thrombocytopenia. Proc Natl Acad Sci U S A. 1997;94: [].