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bioRxiv · 10.1101/2024.10.15.618447

The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV

Mueller, B. R.·Mehta, M.·Campbell, M.·Neupane, N.·Cedillo, G.·Lee, G.·Coyle, K.·Qi, J.·Chen, Z.·George, M. C.·Robinson-Papp, J.
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Abstract

PurposePre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unclear if ANS-immune connections delineated in pre-clinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with HIV. This study had three aims: 1.) Examine the relationship between IL-6 and the parasympathetic/vagal component of baroreflex sensitivity (BRS-V) in people with HIV; 2.) Determine if the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; 3.) Compare the burden of non-AIDS-related co-morbidities between immunotypes. Methods79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A).1 Levels of immune biomarkers were measured in all participants using the Target 96 Inflammation Panel on the Olink proteomics platform and immunotypes were identified using unbiased, non-negative matrix factorization. Mass cytometry (CyTOF) was completed on a subset of participants with and without autonomic neuropathy (N = 10). ResultsReduced BRS-V predicted higher levels of IL-6 (p=0.002). A pro-inflammatory immunotype defined by elevations in type 1 cytokines (IL-6, IL-17) and increased numbers of CD8+ T-cells was associated with autonomic neuropathy characterized by deficits in sympathetic nervous system activity (aOR=4.7, p=0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities. ConclusionDeficits in the parasympathetic/cardiovagal and the sympathetic nervous system are associated with inflammation and disease burden in people living with HIV. Future longitudinal research is needed to examine causality.

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Mueller, B. R., Mehta, M., Campbell, M., Neupane, N., Cedillo, G., Lee, G., Coyle, K., Qi, J., Chen, Z., George, M. C., Robinson-Papp, J.. 2024-10-16. The Autonomic Nervous System (ANS)-Immune Network in People Living With HIV. https://doi.org/10.1101/2024.10.15.618447

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