On the Mechanism of Thrombocytopenic Purpura in Sexually Active Homosexual Men

Walsh, Christina; Nardi, Michael A.; Karpatkin, Simon

doi:10.1056/nejm198409063111004

Cited by 291 publications

(94 citation statements)

References 10 publications

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“…7S anti-platelet IgG was detectable in the PEG-ICs of patients but not in their sera. The absence of anti-platelet IgG in the sera of HIV-1-ITP homosexual patients has been reported by our group (2). The finding of anti-platelet IgG in their PEG-ICs was therefore unexpected.…”

Section: Methodssupporting

confidence: 57%

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Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

Karpatkin

Nardi

Hymes

1995

Proc. Natl. Acad. Sci. U.S.A.

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Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which sequesters serum anti-platelet IgG containing anti-GPIIIa. Anti-platelet IgG contributes to binding of immune complexes to platelets and correlates with thrombocytopenia.

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Section: Methodssupporting

confidence: 57%

“…The disease is different with respect to the markedly elevated IgG, IgM, and C3C4 on their platelets (2,6) and the presence of PEG-precipitable serum immune complexes containing IgG, IgM, and C3C4 (7). Our laboratory has provided evidence for the deposition of immune complexes from their sera onto their platelets (7,8).…”

mentioning

confidence: 99%

Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

Karpatkin

Nardi

Hymes

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…Individuals at risk for the acquired immunodeficiency syndrome (AIDS):' sexually active homosexuals (1)(2)(3), narcotic addicts (4), and multiply transfused hemophiliacs (5,6) develop a new syndrome of idiopathic thrombocytopenic purpura (ITP), which is clinically indistinguishable from classic autoimmune thrombocytopenic purpura (ATP) (7). However, immunologic studies Received for publication 20 November 1985 and in revised form 7 February 1986.…”

Section: Introductionmentioning

confidence: 99%

Anti-F(ab')2 antibodies in thrombocytopenic patients at risk for acquired immunodeficiency syndrome.

Yu¹,

Lennette²,

Karpatkin³

1986

J. Clin. Invest.

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“…Given their occurrence in association with the high antibody and cellular immune responses to HIV Env induced by this DNA primeprotein boost vaccine, along with the recognition that HIV infected individuals display a varied autoimmune antibody repertoire to self-antigens [30][31][32][33][34][35], a potential relationship to HIV Env warrants consideration in the design and analysis of this and other vaccine trials. Representative photographs of skin reactions observed after one protein vaccination in subjects primed with DNA vaccines.…”

mentioning

confidence: 99%

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

Kennedy

Green

et al. 2008

Vaccine

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This report describes the safety observations following administration of a polyvalent DNA primeprotein boost HIV-1 vaccine formulated with adjuvant QS21. Local injection site reactionswere the most common (65% of subjects), and included type IV delayed-type hypersensitivity (DTH) reactions at prior DNA inoculation sites in 12 of 28 (43%) subjects following protein vaccination. Systemic reactions revealed two cases of vasculitis temporally related to inoculation with recombinant Env protein + QS21 adjuvant. Questions remain regarding the cause of the vasculitis, but the unique DTH observation may have contributed to the high level of immune responses previously reported for this vaccine. Keywords HIV; vaccine; adverse event; vasculitisOver the past two decades, various HIV vaccines have been tested for safety and several for efficacy in humans. However, the majority have not reproduced, in humans, the high immunogenicity seen in preclinical testing. Recently, we reported that a novel multi-gene, polyvalent DNA prime-recombinant protein boost HIV vaccine formulation, DP6-001, elicited strong and balanced humoral and cell-mediated immunity in healthy, HIV-1-negative adult subjects [1]. Preclinical testing of DP6-001 demonstrated no significant adverse reactions in either rabbits or non-human primates despite the induction of robust immunity [2,3]. Previously tested HIV DNA vaccines have demonstrated excellent human safety profiles [4][5][6][7][8][9]. Recombinant protein-based HIV vaccines formulated with QS21 adjuvant have reported local reactions, but have shown limited systemic adverse events in humans [10][11][12][13][14][15]. The current report summarizes the phase 1 clinical safety and tolerability data, highlighting local and *Address correspondence to: Jeff Kennedy, M.D., Division of Molecular Medicine, Wadsworth Center, Biggs Laboratory, ESP, C606, NYS Department of Health, P.O. Box 509, Albany, New York 12201-0509, P: 518-473-8421, F: 518-473-2900, E: jsk07@health.state.ny.us. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. The clinical trial was an open-label, 3-arm design requiring each subject to receive two vaccine components; three sequential inoculations using a DNA plasmid vaccine administered either intradermally (ID) or intramuscularly (IM) followed by two sequential inoculations using a protein vaccine as shown in Table 1. Healthy HIV-negative adults (aged 18-50) were enrolled under informed consent as previously described [1]. This study involved 2 dose levels of DNA vaccines (1.2mg (Groups A and B); 7.2mg (Group C)) expressing five gp120 Env ant...

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On the Mechanism of Thrombocytopenic Purpura in Sexually Active Homosexual Men

Cited by 291 publications

References 10 publications

Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

Anti-F(ab')2 antibodies in thrombocytopenic patients at risk for acquired immunodeficiency syndrome.

The safety and tolerability of an HIV-1 DNA prime–protein boost vaccine (DP6-001) in healthy adult volunteers

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