Role of molecular mimicry to HIV-1 peptides in HIV-1-related immunologic thrombocytopenia.
ABSTRACT Patients with early HIV-1 infection develop an autoimmune thrombocytopenia in which antibody is directed against an immunodominant epitope of the beta3 (glycoprotein IIIa [GPIIIa]) integrin, GPIIIa49-66. This antibody induces thrombocytopenia by a novel complement-independent mechanism in which platelets are fragmented by antibody-induced generation of H2O2 derived from the interaction of platelet nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and 12-lipoxygenase. To examine whether sharing of epitope between host and parasite may be responsible for this immunodominant epitope, we screened for antibody-reactive peptides capable of inhibiting platelet lysis and oxidation in vitro, using a filamentous phage display 7-mer peptide library. Fourteen of these phage-peptide clones were identified. Five shared close sequence similarity with GPIIIa49-66, as expected. Ten were molecular mimics with close sequence similarity to HIV-1 proteins nef, gag, env, and pol. Seven were synthesized as 10-mers from their known HIV-1 sequence and found to inhibit anti-GPIIIa49-66-induced platelet oxidation/fragmentation in vitro. Three rabbit antibodies raised against these peptides induced platelet oxidation/fragmentation in vitro and thrombocytopenia in vivo when passively transferred into mice. One of the peptides shared a known epitope region with HIV-1 protein nef and was derived from a variant region of the protein. These data provide strong support for molecular mimicry in HIV-1-immunologic thrombocytopenia within polymorphic regions of HIV-1 proteins. A known epitope of nef is particularly incriminated.
SourceAvailable from: Ruth Aralí Martínez-VegaBiomédica: revista del Instituto Nacional de Salud 04/2011; 31(1):35. DOI:10.7705/biomedica.v31i1.334 · 0.62 Impact Factor
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ABSTRACT: Severe thrombocytopenia (platelets <50x10/L) is relatively frequent during HIV infection and is associated with bleeding risk and disease progression. We investigated the changes in the incidence of severe thrombocytopenia and its predisposing conditions in a cohort of HIV-positive subjects.JAIDS Journal of Acquired Immune Deficiency Syndromes 09/2014; DOI:10.1097/QAI.0000000000000347 · 4.39 Impact Factor
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ABSTRACT: We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda. This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS) Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) technique. We reviewed 15,030 client records. The median age was 35.0 (range 18-78; interquartile range [IQR] 28-42) years, and there were 63.2% (n=9,500) females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%-18.0%). The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%-18.4%) among antiretroviral therapy (ART)-naïve clients (n=2,675) and was 13.0% (95% CI: 0.3%-21.9%) for clients who were on ART (n=6). The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05). Two of the 40 participants (5.0%) had antiplatelet antibodies. This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of thrombocytopenia burden in a high-HIV study population (Southwest Uganda); therefore, there is need to monitor platelet counts and initiate platelet transfusion in our blood banking practices, to avert possible risks of bleeding.Hematology Research and Reviews 01/2015; 6:109-13. DOI:10.2147/JBM.S80857