Autonomic neuropathy is associated with an increase in type-1 cytokines in people living with HIV
Clinical Autonomic Research, 2025
Mueller B., Mehta M., Campbell M., Neupane N., Cedillo G., Lee G., Coyle K., Qi J., Chen Z., George M., Robinson-Papp J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Neurology Infectious Diseases | Pathophysiology Patient Stratification |  Olink Target 96 |
Abstract
Purpose
Pre-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 these preclinical studies underlie the relationship between autonomic dysregulation and chronic inflammatory diseases in patients with human immunodeficiency virus (HIV). The aims of this study were: (1) to examine the relationship between interleukin-6 (IL-6) and the parasympathetic/vagal component of baroreflex sensitivity in people with HIV; (2) to determine whether the subtype and severity of HIV-autonomic neuropathy (AN) would predict distinct immunotypes; and (3) to compare the burden of non-acquired immunodeficiency syndrome (AIDS)-related co-morbidities between immunotypes.
Methods
A total of 79 adults with well-controlled HIV underwent a standard battery of autonomic function tests summarized as the Composite Autonomic Severity Score (CASS) and vagal and adrenergic baroreflex sensitivity (BRS-V and BRS-A, respectively) (Low: Mayo Clin Proc 68:748–752, 1993). 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).
Results
Reduced 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 (adjusted odds ratio 4.7, p = 0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities.
Conclusion
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.