Targeted plasma proteomics reveals upregulation of distinct inflammatory pathways in people living with HIV
Nadira Vadaq,
Lisa van de Wijer,
Louise E. van Eekeren,
Hans Koenen,
Quirijn de Mast,
Leo A.B. Joosten,
Mihai G. Netea,
Vasiliki Matzaraki,
André J.A.M. van der Ven
Affiliations
Nadira Vadaq
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands; Center for Tropical and Infectious Diseases (CENTRID), Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia; Corresponding author
Lisa van de Wijer
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands
Louise E. van Eekeren
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands
Hans Koenen
Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands
Quirijn de Mast
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands
Leo A.B. Joosten
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Medical Genetics, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
Mihai G. Netea
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands; Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Germany
Vasiliki Matzaraki
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands
André J.A.M. van der Ven
Department of Internal Medicine, Radboudumc Center for Infectious Diseases, Radboud Institute of Health Science (RIHS), Radboud University Medical Center, Nijmegen, the Netherlands; Corresponding author
Summary: Despite antiretroviral therapy (ART), people living with HIV (PLHIV) display persistent inflammation leading to non-AIDS-related co-morbidities. To better understand underlying mechanisms, we compared targeted plasma inflammatory protein concentration (n = 92) between a cohort of 192 virally suppressed PLHIV, who were followed-up for five years, and 416 healthy controls (HC). Findings were validated in an independent cohort of 649 virally suppressed PLHIV and 98 HC. Compared to HC, PLHIV exhibited distinctively upregulated inflammatory proteins, including mucosal defense chemokines, CCR5 and CXCR3 ligands, and growth factors. Unsupervised clustering of inflammatory proteins clearly differentiated PLHIV with low (n = 123) and high inflammation (n = 65), the latter having a 3.4 relative risk (95% confidence interval 1.2–9.8) to develop malignancies and trend for cardiovascular events during a 5-year follow-up. The best protein predictors discriminating the two inflammatory endotypes were PD-L1, VEGFA, LAP TGF β-1, and TNFRSF9. Our data provide insights into co-morbidities associated inflammatory changes in PLHIV on long-term ART.
