Autoantibody-mediated platelet phagocytosis in SIV-infected macaques

Dittmer, Ulf; Coulibaly, Cheick; Sauermann, Ulrike; Stahl–Hennig∥, Christiane; Petry, Harald; Hunsmann, Gerhard; Fj, Kaup

doi:10.1097/00002030-199410000-00026

Cited by 7 publications

(3 citation statements)

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“…As is also commonly observed in HIV-infection [31],[32], many SIV-infected macaques exhibited thrombocytopenia during their disease course [33],[34]. As shown in Figure 7A, a progressive decline was observed throughout the course of infection in ND macaques and the platelet count at the time of death was significantly lower in ND than MD macaques (Figure 7B).…”

Section: Resultssupporting

confidence: 69%

“…Primary clinical manifestations which have been observed in HIV-infection include thrombocytopenia, anemia, systemic vasculitis, Reiter's syndrome, polyarthritis, Sjogren's syndrome and antiphospholipid syndrome (APS) [32] . Autoantibodies and autoimmune diseases have also been demonstrated in SIV-infected macaques [33] , [34] , [39] . In the present study, we observed an association of anti-platelet and antiphospholipid antibodies with clinical autoimmune disease, specifically thrombocytopenia and APS in macaques.…”

Section: Discussionmentioning

confidence: 99%

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Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

et al. 2009

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The progressive decline of CD4+ T cells is a hallmark of disease progression in human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infection. Whereas the acute phase of the infection is dominated by virus-mediated depletion of memory CD4+ T cells, chronic infection is often associated with a progressive decline of total CD4+ T cells, including the naïve subset. The mechanism of this second phase of CD4+ T cell loss is unclear and may include immune activation–induced cell death, immune-mediated destruction, and regenerative or homeostatic failure. We studied patterns of CD4+ T cell subset depletion in blood and tissues in a group of 20 rhesus macaques inoculated with derivatives of the pathogenic SIVsmE543-3 or SIVmac239. Phenotypic analysis of CD4+ T cells demonstrated two patterns of CD4+ T cell depletion, primarily affecting either naïve or memory CD4+ T cells. Progressive decline of total CD4+ T cells was observed only in macaques with naïve CD4+ T cell depletion (ND), though the depletion of memory CD4+ T cells was profound in macaques with memory CD4+ T cell depletion (MD). ND macaques exhibited lower viral load and higher SIV-specific antibody responses and greater B cell activation than MD macaques. Depletion of naïve CD4+ T cells was associated with plasma antibodies autoreactive with CD4+ T cells, increasing numbers of IgG-coated CD4+ T cells, and increased incidence of autoreactive antibodies to platelets (GPIIIa), dsDNA, and phospholipid (aPL). Consistent with a biological role of these antibodies, these latter antibodies were accompanied by clinical features associated with autoimmune disorders, thrombocytopenia, and catastrophic thrombotic events. More importantly for AIDS pathogenesis, the level of autoreactive antibodies significantly correlated with the extent of naïve CD4+ T cell depletion. These results suggest an important role of autoreactive antibodies in the CD4+ T cell decline observed during progression to AIDS.

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Section: Resultssupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

et al. 2009

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“…In our study cohort, 80 % of the macaques with endocarditis also showed TCP. HIV-and SIV-associated TCP develops through multiple mechanisms, including autoantibodies, decreased platelet production in the bone marrow and/or increased platelet destruction in the spleen and in the periphery (e.g., blood or lymph nodes) (Dittmer et al, 1994;Metcalf Pate and Mankowski, 2011). Notably, to our knowledge, an association between endocarditis and SIV-associated TCP has not been described before.…”

Section: Endocarditis Thrombocytopenia and Cd4 / Cd8 Ratiomentioning

confidence: 86%

Revisiting a quarter of a century of simian immunodeficiency virus (SIV)-associated cardiovascular diseases at the German Primate Center

et al. 2017

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Abstract. Human immunodeficiency virus (HIV) comorbidities have become clinically more important due to antiretroviral therapy. Although therapy increases life expectancy, it does not completely suppress immune activation and its associated complications. The simian immunodeficiency virus (SIV)-infected rhesus macaque (Macaca mulatta) represents a valuable model for the investigation of SIV-associated diseases. Although cardiovascular (CV) changes are common in HIV-infected patients, there are only a few reports on the incidence of CV findings in SIV-infected animals. In addition, potential associations between pathohistological findings and hematological parameters are still unclear.We therefore conducted a retrospective analysis of 195 SIV-infected rhesus macaques that were euthanized with AIDS-related symptoms at the German Primate Center, Goettingen, over a 25-year period. Pathological findings were correlated with hematological data.The main findings included myocarditis (12.8 %), endocarditis (9.7 %), and arteriopathy (10.3 %) in various organs. Thrombocytopenia occurred more frequently in macaques with endocarditis or arteriopathy than in macaques without CV disease (80 % in animals with endocarditis, 60 % in animals with arteriopathy, p < 0.0001 and p = 0.0016, respectively).Further investigations of the interaction between coagulation markers, proinflammatory cytokines, and biomarkers associated with endothelial dysfunction (e.g., D-dimers) and histological data (vascular wall structure) may unravel the mechanisms underlying HIV/SIV-associated CV comorbidities.

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Social Networks of Substance-Using Populations: Key Issues and Promising New Approaches for HIV

West

2019

Curr HIV/AIDS Rep

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Purpose of Review-This paper presents recent literature on substance using networks and HIV, highlighting renewed and emerging themes in the field. The goal is to draw attention to research that holds considerable promise for advancing our understanding of the role of networks in shaping behaviors, while also providing critical information for the development of interventions, programs, and policies to reduce HIV and other drug-related harms. Recent Findings-Recent research advances our understanding of networks and HIV, including among understudied populations, and provides new insight into how risk environments shape the networks and health of substance-using populations. In particular, the integration of network approaches with molecular epidemiology, research on space and place, and intervention methods provides exciting new avenues of investigation. Summary-Continued advances in network research are critical to supporting the health and rights of substance-using populations and ensuring the development of high-impact HIV programs and policies.

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Autoantibody-mediated platelet phagocytosis in SIV-infected macaques

Cited by 7 publications

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Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

Association of Progressive CD4+ T Cell Decline in SIV Infection with the Induction of Autoreactive Antibodies

Revisiting a quarter of a century of simian immunodeficiency virus (SIV)-associated cardiovascular diseases at the German Primate Center

Social Networks of Substance-Using Populations: Key Issues and Promising New Approaches for HIV

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