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

Pre-clinical studies have demonstrated direct influences of the autonomic nervous system (ANS) on the immune system. However, it remains unknown if connections between the peripheral ANS and immune system exist in humans and contribute to the development of chronic inflammatory disease. This study had three aims: 1.) To examine the relationship between IL-6 and the parasympathetic/vagal component of baroreflex sensitivity (BRS-V) in people with HIV; 2.) To determine if the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; 3.) To compare the burden of non-AIDS-related co-morbidities between immunotypes.

79 adult people 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). 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).

First, we found reduced BRS-V predicted higher levels of IL-6 (p = 0.002). Second, 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.

Deficits 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.