Fig 1: Serum β-NGF and fractalkine/CX3CL1 levels, HTLV-1 proviral load, and CSF IL-18 concentration in HAM/TSP patients according to altered markers of inflammation and neurodegeneration. Individuals were separated according to normal (n = 7, purple) and altered (n = 13, red) CSF levels of neurofilament light (NfL) proteins and considering active neuroinflammation as a CSF/serum ratio of neopterin ≥1 (n = 13, red) or CXCL10 ≥ 2 (n = 9, red). Patients with a CSF/serum ratio of neopterin <1 (n = 7, purple) or CXCL10 < 2 (n = 11, purple) were considered to have low neuroinflammatory activity. Finally, individuals were also discriminated by normal CSF cell counts (<5 cells/mm3) (n = 12, purple) or pleocytosis (n = 8, red). (A) Serum β-NGF, (B) HTLV-1 proviral load (PVL), and (C,D) serum fractalkine/CX3CL1 levels were compared between groups with Student’s t-test. (E,F) CSF IL-18 levels were compared between groups with the Mann–Whitney test. Differences with p < 0.05 were considered significant.
Fig 2: Correlation analysis between serum levels of inflammatory chemokines and factors associated with neuroinflammation. Correlation between serum levels of TGF-β1, IL-18, BDNF, β-NGF, VEGF, sTREM-2, IL-6, sRAGE, TNF-α, CX3CL1 (fractalkine), sTREM-1, and chemokines (CXCL9, CXCL10, and CXCL11) was evaluated in (A) asymptomatic HTLV-1 carriers (AC) (n = 13) and (B) HAM/TSP patients (n = 20) using the Spearman’s rank correlation test. Correlation coefficients are indicated by color intensity, in which positive correlations are shown in red and negative correlations in blue. The size of the squares at intersections between factors represents the p-value, which is shown only for significant associations (p < 0.05).
Fig 3: CSF levels of factors associated with neuroinflammation. (A) VILIP-1, (B) sRAGE, (C) sTREM-1, (D) sTREM-2, (E) BDNF, (F) VEGF, (G) β-NGF, (H) IL-6, (I) IL-18, (J) TNF-α, (K) TGF-β1, and (L) fractalkine (CX3CL1) levels were simultaneously determined with a multiplex bead-based immunoassay by flow cytometry in cerebrospinal fluid (CSF) samples from asymptomatic HTLV-1 carriers (AC) (n = 13), HAM/TSP patients (n = 20), and a control group of HTLV-1-seronegative individuals (n = 9). A normal distribution was determined by the Kolmogorov–Smirnov test. Statistical analysis of parametric variables was performed with ANOVA and Bonferroni’s post-test, and non-parametric data were evaluated by the Kruskal–Wallis test and Dunn’s post-test. Results with a p-value < 0.05 were considered significant.
Fig 4: Correlation analysis of biomarkers of neuroinflammation in serum. (A) Correlation between TGF-β1, IL-18, BDNF, β-NGF, VEGF, sTREM-2, IL-6, sRAGE, TNF-α, CX3CL1 (Fractalkine), and sTREM-1 levels in serum samples from asymptomatic HTLV-1 carriers (AC) (n = 13) and HAM/TSP patients (n = 20) was performed with Spearman’s rank correlation test. (B) The analysis was also performed with the serum neopterin concentration and HTLV-1 proviral load (PVL) in PBMCs from HTLV-1 AC and HAM/TSP patients. Correlation coefficients are indicated by the color intensity, in which positive correlations are shown in red and negative correlations in blue. The size of the squares at intersections between factors represents the p-value, which is shown only for significant associations (p < 0.05).
Fig 5: Correlation between CSF levels of inflammatory chemokines and factors associated with neuroinflammation. Correlation between CSF levels of TGF-β1, IL-18, BDNF, VEGF, IL-6, sTREM-2, sTREM-1, and chemokines (CCL2, CCL3, CCL4, CCL17, CXCL5, CXCL10, and CXCL11) was evaluated in (A) asymptomatic HTLV-1 carriers (AC) (n = 13) and (B) HAM/TSP patients (n = 20) with Spearman’s rank correlation test. Correlation coefficients are indicated by color intensity, in which positive correlations are shown in red and negative correlations in blue. The size of the squares at intersections between factors represents the p-value, which is shown only for significant associations (p < 0.05).
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