The 2-hydroxy-nevirapine metabolite as a candidate for boosting apolipoprotein A1 and for modulating anti-HDL antibodies

Marinho, Aline T.; Batuca, Joana R.; Miranda, Joana P.; Caixas, Umbelina; Dias, Clara G.; Branco, Teresa; Soto, Karina; Pinheiro, Pedro F.; Bourbon, Mafalda; Marques, M. Matilde; Antunes, Alexandra M. M.; Monteiro, Emília C.; Pereira, Sofia A.

doi:10.1016/j.phrs.2021.105446

Cited by 2 publications

(1 citation statement)

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“…Although the present study did not investigate underlying molecular mechanisms, previous publications showed that ICAM-1 and VCAM-1 expression is TLR2/TLR4-dependent ( 39 – 41 ), suggesting that the same innate immune receptors could be involved in anti-apoA1 IgG-induced trans-endothelial migration of immunocompetent cells. The impact of ART on auto-antibodies is poorly documented; however, the observation in our study is in line with the findings of Marinho and colleagues ( 42 ), who showed that the anti-retroviral nevirapine (NVP) was able to lower the titres of anti-HDL auto-antibodies, which are closely related to anti-apoA1 antibodies. However, since only one participant in the current study cohort was treated with NVP, we could not replicate this observation with anti-apoA1 IgG.…”

Section: Discussionsupporting

confidence: 93%

People living with HIV display increased anti-apolipoprotein A1 auto-antibodies, inflammation, and kynurenine metabolites: a case–control study

Frias,

Pagano,

Bararpour

et al. 2024

Front. Cardiovasc. Med.

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ObjectiveThis study aimed to study the relationship between auto-antibodies against apolipoprotein A1 (anti-apoA1 IgG), human immunodeficiency virus (HIV) infection, anti-retroviral therapy (ART), and the tryptophan pathways in HIV-related cardiovascular disease.DesignThis case–control study conducted in South Africa consisted of control volunteers (n = 50), people living with HIV (PLWH) on ART (n = 50), and untreated PLWH (n = 44). Cardiovascular risk scores were determined, vascular measures were performed, and an extensive biochemical characterisation (routine, metabolomic, and inflammatory systemic profiles) was performed.MethodsAnti-apoA1 IgG levels were assessed by an in-house ELISA. Inflammatory biomarkers were measured with the Meso Scale Discovery® platform, and kynurenine pathway metabolites were assessed using targeted metabolomic profiling conducted by liquid chromatography-multiple reaction monitoring/mass spectrometry (LC-MRM/MS).ResultsCardiovascular risk scores and vascular measures exhibited similarities across the three groups, while important differences were observed in systemic inflammatory and tryptophan pathways. Anti-apoA1 IgG seropositivity rates were 15%, 40%, and 70% in control volunteers, PLWH ART-treated, and PLWH ART-naïve, respectively. Circulating anti-apoA1 IgG levels were significantly negatively associated with CD4+ cell counts and positively associated with viremia and pro-inflammatory biomarkers (IFNγ, TNFα, MIPα, ICAM-1, VCAM-1). While circulating anti-apoA1 IgG levels were associated with increased levels of kynurenine in both control volunteers and PLWH, the kynurenine/tryptophan ratio was significantly increased in PLWH ART-treated.ConclusionHIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.

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Section: Discussionsupporting

confidence: 93%