Serological Markers for Inflammatory Bowel Disease in AIDS Patients with Evidence of Microbial Translocation

Kamat, Anupa; Ancuța, Petronela; Blumberg, Richard S.; Gabuzda, Dana

doi:10.1371/journal.pone.0015533

Cited by 32 publications

(21 citation statements)

References 87 publications

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“…41,42 It has been proposed that the intestinal barrier defect in HIV infection may resemble that of IBD. 43 However, our data suggest that although LPS levels were higher in IBD patients than in HIV-1-infected subjects, the consequences are different. IBD patients had lower levels of MD2, sCD14 and I-FABP, suggesting less immune activation and ongoing gut damage.…”

Section: Discussionmentioning

confidence: 55%

Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: Possible implication for TLR4-signalling and chronic immune activation

et al. 2012

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Progressive HIV infection is characterized by profound enterocyte damage, microbial translocation and chronic immune activation. We aimed to test whether High Mobility Group Box protein 1(HMGB1), a marker of cell death, alone, or in combination with LPS, might contribute to HIV-associated immune activation and progression. Altogether, 29 untreated HIV-infected individuals, 25 inflammatory bowel disease (IBD) patients and 30 controls were included. HIV-infected patients had lower plasma LPS levels than IBD patients, but higher levels of soluble CD14 and Myeloid Differentiation (MD) 2, which interacts with TLR4 to initiate LPS-signalling. Furthermore, plasma levels of HMGB1 and MD2 were correlated directly within the HIV-infected cohort (r = 0.89, P < 0.001) and the IBD-cohort (r = 0.85, P < 0.001), implying HMGB1 signalling through the MD2/TLR4-pathway. HMGB1 and LPS, although not inter-correlated, were both moderately (r = 0.4) correlated with CD38 density on CD8+ T cells in HIV progressors. The highest levels of CD38 density and MD2 were found in progressors with plasma levels of both LPS and HMGB1 above the fiftieth percentile. Our results could imply that, in some patients, immune activation is triggered by microbial translocation, in some by cell death and in some by HMGB1 in complex with bacterial products through activation of the MD2/TLR4-pathway.

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Section: Discussionmentioning

confidence: 55%

Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: Possible implication for TLR4-signalling and chronic immune activation

et al. 2012

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“…Also, Kamat et al [39] reported recently the presence of a subgroup of anti-flagellin antibodies (anti-CBir1) in 4/26 HIV-1-infected patients with CD4+ T-cells counts <300 cells/ul and high LPS levels. The CBir1 flagellin has been identified as an immune dominant flagellin in Crohn's disease and linked to Clostridia species.…”

Section: Discussionmentioning

confidence: 99%

Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection

Nowak

Abdurahman

Lindkvist

et al. 2012

International Journal of Microbiology

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Objective. We hypothesized that HMGB1 in complex with bacterial components, such as flagellin, CpG-ODN, and LPS, promotes HIV-1 replication. Furthermore, we studied the levels of antiflagellin antibodies during HIV-1-infection. Methods. Chronically HIV-1-infected U1 cells were stimulated with necrotic extract/recombinant HMGB1 in complex with TLR ligands or alone. HIV-1 replication was estimated by p24 antigen in culture supernatants 48–72 hours after stimulation. The presence of systemic anti-flagellin IgG was determined in 51 HIV-1-infected patients and 19 controls by immunoblotting or in-house ELISA. Results. Flagellin, LPS, and CpG-ODN induced stronger HIV-1 replication when incubated together with necrotic extract or recombinant HMGB1 than activation by any of the compounds alone. Moreover, the stimulatory effect of necrotic extract was inhibited by depletion of HMGB1. Elevated levels of anti-flagellin antibodies were present in plasma from HIV-1-infected patients and significantly decreased during 2 years of antiretroviral therapy. Conclusions. Our findings implicate a possible role of HGMB1-bacterial complexes, as a consequence of microbial translocation and cell necrosis, for immune activation in HIV-1 pathogenesis. We propose that flagellin is an important microbial product, that modulates viral replication and induces adaptive immune responses in vivo.

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“…Additionally, it has recently reported that HAND is associated with higher systemic levels of plasma LPS [37]. The hypothesis is that HIV-1 infected patients with microbial translocation from the gut will have higher plasma LPS and thus more systemic immune activation leading to increased risk of transit of HIV-infected monocytes into end organs including the CNS [38]. Another study suggests that HIV-1 infection increases the vulnerability of the BBB in response to LPS and facilitates the transmigration of peripheral monocytes/macrophages [39].…”

Section: Neuropathogenesismentioning

confidence: 99%

Update on HIV-Associated Neurocognitive Disorders

Alfahad

Nath

2013

Curr Neurol Neurosci Rep

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Neurocognitive disorders are a feared complication of HIV infection, especially in the post anti-retroviral era as patients are living longer. These disorders are challenging in terms of diagnosis and treatment. The clinical syndrome has evolved driven in part by comorbidities such as aging, drug abuse, psychiatric illnesses, and a metabolic syndrome associated with the use of antiretroviral drugs. Additionally some individuals may develop a fulminant immune reconstitution syndrome. Hence management of these patients needs to be individualized. The focus of research in the HIV field has recently switched towards elimination of the HIV reservoir as a means of combating long-term HIV complications. However these approaches maybe suitable for limited populations and might not be applicable once the HIV reservoir has been established in the brain. Further, all clinical trials using neuroprotective or anti-inflammatory drugs for treatment of HIV-associated neurocognitive disorders have been unsuccessful. Hence neurological complications of HIV infection represent the biggest challenge facing HIV researchers and there is a critical need for developing new diagnostics and approaches to treatment for these disorders.

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Serological Markers for Inflammatory Bowel Disease in AIDS Patients with Evidence of Microbial Translocation

Cited by 32 publications

References 87 publications

Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: Possible implication for TLR4-signalling and chronic immune activation

Circulating levels of HMGB1 are correlated strongly with MD2 in HIV-infection: Possible implication for TLR4-signalling and chronic immune activation

Impact of HMGB1/TLR Ligand Complexes on HIV-1 Replication: Possible Role for Flagellin during HIV-1 Infection

Update on HIV-Associated Neurocognitive Disorders

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