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

Miguel A Frias; Sabrina Pagano; Nasim Bararpour; Jonathan Sidibé; Festus Kamau; Vanessa Fétaud-Lapierre; Peter Hudson; Aurélien Thomas; Sandrine Lecour; Hans Strijdom; Nicolas Vuilleumier

doi:10.3389/fcvm.2024.1343361

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

Front Cardiovasc Med. 2024 Feb 13:11:1343361. doi: 10.3389/fcvm.2024.1343361. eCollection 2024.

Authors

Miguel A Frias^{1

2}, Sabrina Pagano^{1

2}, Nasim Bararpour^{3

4

5}, Jonathan Sidibé³, Festus Kamau⁶, Vanessa Fétaud-Lapierre^{1

2}, Peter Hudson⁷, Aurélien Thomas^{3

8}, Sandrine Lecour⁷, Hans Strijdom⁶, Nicolas Vuilleumier^{1

2}

Affiliations

¹ Division of Laboratory Medicine, Diagnostic Department, Geneva University Hospitals, Geneva, Switzerland.
² Department of Medical Specialties, Faculty of Medicine, University of Geneva, Geneva, Switzerland.
³ Faculty Unit of Toxicology, CURML, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
⁴ Department of Genetics, Stanford University, Stanford, CA, United States.
⁵ Stanford Center for Genomics and Personalized Medicine, Stanford, CA, United States.
⁶ Centre for Cardiometabolic Research in Africa, Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.
⁷ Cape Heart Institute, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
⁸ Unit of Forensic Toxicology and Chemistry, CURML, Lausanne and Geneva University Hospitals, Lausanne, Geneva, Switzerland.

Abstract

Objective: This 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.

Design: This 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.

Methods: Anti-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).

Results: Cardiovascular 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.

Conclusion: HIV infection increases the humoral response against apoA1, which is associated with established HIV severity criteria and kynurenine pathway activation.

Keywords: HIV; anti-apolipoprotein A1 auto-antibodies; anti-retroviral therapy; autoimmunity; cardiovascular disease; kynurenine pathway metabolites.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article.