Autonomic Neuropathy Is Associated with An Increase in Type-1 Cytokines in People Living With HIV

Figures

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  Figure 1:. Lower vagal baroreflex sensitivity (BRS-V) is associated with higher plasma interleukin-(IL-6).

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  Figure 2.. Heat map of 92 plasma immune biomarkers demonstrates four distinct immunotypes revealed by NMF clustering analysis and an elevation in type 1 cytokines in immunotype 1 (e.g. IL-6, IL-17) compared to other immunotypes (p < 0.05; see Supplemental Table 1) Immunotype 2 also exhibited increased pro-inflammatory markers, but at a lower level than immunotype 1, and showed an increase in anti-inflammatory markers compared to immunotype 1 (e.g. IL-10 p < 0.05). Colored vertical bars indicate the biomarkers whose elevation defined the four immunotype groups. Horizontal bars indicate the participants within each immunotype. Blue represents decreased relative protein expression while red represents increased expression.

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  Figure 3:. Gene Ontology (GO) analysis demonstrates increased expression of type 1 pro-inflammatory cytokines in immunotype 1 (A) and upregulation of proteins involved in the inhibition of pro-inflammatory cytokines, apoptosis, and immune signaling in immunotypes 2 (B) and 3 (C). Immunotype 4 (D) had an increased expression of proteins involved in intracellular signaling and immunoglobulin secretion.

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  Figure 4.. ANS testing revealed distinct patterns of parasympathetic/vagal, non-cardiovascular sympathetic (i.e. sudomotor), and cardiovascular sympathetic (i.e. adrenergic) deficits, as defined by a CASS sub-score ≥1, in immunotypes 1–4. Diagonal lines indicate prevalence of moderate-severe deficits (CASS sub-score ≥2) * p < 0.001 indicates a significantly higher prevalence of cardiovascular sympathetic (i.e. adrenergic) deficits in immunotype 1 compared to immunotypes 2, 3, and 4.

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  Figure 5.. Comparison of immune cell type between participants with normal autonomic function and patients with autonomic neuropathy. * p < 0.01 indicates significant increase in proportion of CD3+ CD8+ and CD8 EMRA (terminally differentiated effector memory T cell) sub-populations of T cells. Autonomic neuropathy is defined as CASS ≥ 3. Normal ANS function defined as CASS ≤ 1.