Plasmatic proinflammatory chemokines levels are tricky markers to monitoring HTLV-1 carriers

Abstract

The human T-cell leukemia virus type 1 (HTLV-1) is present throughout the world and is associated with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and other inflammatory conditions. The pathogenesis of HAM/TSP involves a chronic inflammatory response in central nervous system (CNS), with the presence of HTLV-1 infected cells and HTLV-1-specific CD8+ lymphocytes. Chemokines may have a role in the infiltration of these cells into the CNS. In this context, the present study analyzed the level of plasmatic chemokines CCL2 (MCP-1), CCL5 (RANTES), IL8 (CXCL8), CXCL9 (MIG), and CXCL10 (IP-10) and HTLV-1 proviral load from peripheral blood in 162 asymptomatic carriers and 136 HAM/TSP patients to determine the differences that be associated with the clinical status of the HTLV-1 infection. The results showed that patients with HAM/TSP have significantly higher levels of IL8 and CXCL9, and that the level of IL8, CXCL9 and CXCL10 was significantly greater in HTLV-1 infected individuals with high (>1%) than those with low proviral load (<1%). However, the levels of the chemokines tested have not showed high sensitivity to discriminate HAM/TSP patients from asymptomatic carriers. In addition, chemokine profiles in asymptomatic carriers and HAM/TSP groups were similar, with no significant increased frequency of higher producers of chemokines in HAM/TSP individuals. Results indicate that the heterogeneity of the individuals in the groups regarding time of infection, duration of disease, proviral load level and other possible confound factors may impair the use of chemokines levels to monitor HTLV-1 carriers in clinical practice. J. Med. Virol. 88:1438-1447, 2016. © 2016 Wiley Periodicals, Inc.

Altered expression of CXCR3 and CCR6 and their ligands in HTLV‐1 carriers and HAM/TSP patients

“…However, the CD4 T cell responses to HTLV‐1, the predominant subset of lymphocytes infiltrating the CNS, are important for activating CTLs, monocytes, and B cells early in the development and progression of HAM/TSP. These infected CD4 + T cells spontaneously secrete proinflammatory cytokines and chemokines in the CNS and the blood, such as IFN‐γ, TNF‐α, and GM‐CSF, and chemokines such as IL‐8, monocyte chemoattractant protein‐1 (MCP‐1 or CCL2), macrophage inflammatory protein 1 alpha (MIP‐1a or CCL3) and beta (MIP‐1ß or CCL4), CCL2 and CCL5 . Therefore, an increase in HTLV‐1‐infected CD4+ T cells, which consequently heightens transmigrating activity to the spinal cord, might play a pivotal role in triggering inflammatory reactions and inducing HAM/TSP development…”

“…Healthy controls, in this study, were a homogenous population compared to HAM/TSP patients and HTLV‐1 carriers and there were not confounding variables to affects the significant differences in CXCR3 expression. It is more likely the some factors such as proviral load, clinical status of HAM/TSP patients, treatment of the patients with immmunomodulatory drugs, duration of the disease and infection, and genetic background of the HTLV‐1 infected individuals may influence in creating controversial results regarding the association of chemokines and their receptors in HTLV‐1 infection …”

The Role of Chemokines in the Pathogenesis of HTLV-1

“…CXCL9 and CXCL10 are presented in high levels in serum and CSF of patients with HAM/TSP and contribute to the pathogenesis of HAM/TSP Guerra et al, 2018). Chaves et al showed that the plasma levels of CXCL8 and CXCL9 were greater in HAM/TSP patients compared to carriers (Chaves et al, 2016). Moreover, a correlation was observed between plasma levels of CXCL8, CXCL9, and CXCL10 and proviral load, in which the HTLV-1 infected individuals with higher proviral loads had increased plasma levels of these chemokines (Chaves et al, 2016).…”

“…Chaves et al showed that the plasma levels of CXCL8 and CXCL9 were greater in HAM/TSP patients compared to carriers (Chaves et al, 2016). Moreover, a correlation was observed between plasma levels of CXCL8, CXCL9, and CXCL10 and proviral load, in which the HTLV-1 infected individuals with higher proviral loads had increased plasma levels of these chemokines (Chaves et al, 2016). CXCL10 in the CSF, as indicators of CNS inflammation, correlate with disease progression and has been suggested as a candidate for the prognosis of HAM/TSP development (Guerreiro et al, 2006;Sato et al, 2013;Lima et al, 2017).…”

“…CXCL8 might be associated with BBB disruption through the attraction of neutrophils within the CNS (Chaves et al, 2016). CXCL8 and its receptors, CXCR1 and CXCR2, are involved in the infiltration of leukocytes into the CNS (Almasi et al, 2013).…”