Lessons from the Cerebrospinal Fluid Analysis of HTLV-1-Infected Individuals: Biomarkers of Inflammation for HAM/TSP Development

• Published in: Viruses Vol. 14; no. 10; p. 2146
• Main Authors: Freitas, Nicole Lardini, Gomes, Yago Côrtes Pinheiro, Souza, Flávia Dos Santos, Torres, Rafael Carvalho, Echevarria-Lima, Juliana, Leite, Ana Claudia Celestino Bezerra, Lima, Marco Antonio Sales Dantas, Araújo, Abelardo Queiroz Campos, Silva, Marcus Tulius Teixeira, Espíndola, Otávio de Melo
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.09.2022; MDPI
• Subjects: Biological markers; Biomarkers; Blood-brain barrier; Brain-Derived Neurotrophic Factor; Central nervous system; Central nervous system diseases; Cerebrospinal fluid; Chemokine CX3CL1; Chemokines; Chi-square test; Correlation analysis; CXCL10 protein; Cytokines; Disease; Fractalkine; HAM/TSP; Health aspects; Homeostasis; HTLV-1; HTLV-I infections; HTLV-I Infections - pathology; Human T-lymphotropic virus 1; Humans; Infections; inflammasome; Inflammasomes; Inflammation; Interleukin 18; Interleukin 6; Medical research; Medicine, Experimental; Neopterin; Neopterin - cerebrospinal fluid; Nerve Growth Factor; Neurocalcin; Neurodegeneration; Neurodegenerative Diseases; Paraparesis, Tropical Spastic; Pathogenesis; Permeability; Physiological aspects; Proteins; Software; Spastic paraparesis; Spinal cord; Statistical analysis; Testing; Transforming Growth Factor beta1; Transforming growth factor-b1; Triggering Receptor Expressed on Myeloid Cells-1; Tropical spastic paraparesis; Tumor Necrosis Factor-alpha; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A; Brazil; United States > US; IL-18; biomarkers; inflammasome; cerebrospinal fluid; neurodegeneration; HAM/TSP; HTLV-1
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v14102146

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease that leads to motor impairment due to a chronic inflammatory process in the central nervous system (CNS). However, the HAM/TSP pathogenesis is not completely clear, and biomarkers to define the disease prognosis are still necessary. Thus, we aimed to identify biomarkers for HAM/TSP and potential mechanisms involved in disease development. To that end, the concentrations of VILIP-1, BDNF, VEGF, β-NGF, TGF-β1, fractalkine/CX3CL1, IL-6, IL-18, and TNF-α, and the soluble forms of TREM-1, TREM-2, and RAGE, were assessed using a multiplex bead-based immunoassay in paired cerebrospinal fluid (CSF) and serum samples from HAM/TSP patients (n = 20), asymptomatic HTLV-1 carriers (AC) (n = 13), and HTLV-1-seronegative individuals (n = 9), with the results analyzed according to the speed of HAM/TSP progression. HAM/TSP patients had elevated fractalkine in the serum but not in the CSF, particularly those with low neuroinflammatory activity (CSF/serum ratio of neopterin <1 and of CXCL10 < 2). HAM/TSP patients with normal CSF levels of neurofilament light chain (NfL) showed elevated β-NGF in serum, and serum BDNF levels were increased in HTLV-1-infected individuals, particularly in HTLV-1 AC. Both HTLV-1 AC and HAM/TSP patients had lower TGF-β1 levels in CSF compared to uninfected individuals, and HAM/TSP patients with active CNS inflammation showed higher CSF levels of IL-18, which correlated with markers of inflammation, neuronal death, and blood−brain-barrier permeability. Although none of the factors evaluated were associated with the speed of HAM/TSP progression, reduced TGF-β1 levels in CSF suggest that suppressive responses to control subclinical and/or active neurodegeneration are impaired, while increased CSF IL-18 indicates the involvement of inflammasome-mediated mechanisms in HAM/TSP development.