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Purpose <p>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.</p> Methods <p>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:<i> Mayo Clin Proc</i> 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 (<i>N</i> = 10).</p> Results <p>Reduced BRS-V predicted higher levels of IL-6 (<i>p</i> = 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, <i>p</i> = 0.017). This pro-inflammatory immunotype was older with a greater burden of co-morbidities.</p> Conclusion <p>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.</p>

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Autonomic neuropathy is associated with an increase in type-1 cytokines in people living with HIV

  • 期刊论文

  • 发表日期：

    2025年5月10日

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  • Bridget R. Mueller,
  • Mitali Mehta,
  • Maya Campbell,
  • Niyati Neupane,
  • Gabriela Cedillo,
  • Gina Lee,
  • Kaitlyn Coyle,
  • Jinging Qi,
  • Zhihong Chen,
  • Mary Catherine George,
  • Jessica Robinson-Papp

摘要

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.