Strong correlation between tax and HBZ mRNA expression in HAM/TSP patients: distinct markers for the neurologic disease.

BACKGROUND: HTLV-1 proviral load is a risk marker for HAM/TSP, but it is insufficient to determine the disease outcome. HTLV-1 Tax and HBZ proteins have been implicated in HAM/TSP pathogenesis in inducing cell proliferation and cytotoxic T lymphocytes response. OBJECTIVES: To quantify the expression of tax and HBZ mRNA in asymptomatic carriers (AC) and HAM patients, and to investigate their association with HAM/TSP. STUDY DESIGN: We quantified the expression of HTLV-1 tax and HBZ mRNA in 37 AC and 26 HAM patients classified according to proviral load as low (AC(L) and HAM(L): <1% infected cells) or high (AC(H) and HAM(H): >1%). RESULTS: The AC(L) subgroup showed the lowest frequency of individuals expressing tax mRNA in comparison with AC(H), HAM(L) and HAM(H), and tax mRNA load normalized by proviral load was significantly lower in the AC(L). In turn, normalized HBZ mRNA expression was similar in all subgroups. Both tax and HBZ mRNA expression were moderately correlated with proviral load in AC (r=0.6, p<0.001) and were weaker in HAM (r=0.4, p<0.05). In contrast, the correlation between tax and HBZ mRNA load was moderate in AC (r=0.5, p=0.001) and was much stronger in HAM (r=0.8, p<0.001). In addition, HBZ mRNA load, but not tax, was significantly associated with motor disability in HAM patients (p=0.036). CONCLUSIONS: The expression of tax mRNA seems to be best to estimate the risk of HAM/TSP, whereas HBZ mRNA appears to be a surrogate marker to disease progression, indicating that they have important but distinct roles in HAM/TSP pathogenesis.

Monitoring the HTLV-1 proviral load in the peripheral blood of asymptomatic carriers and patients with HTLV-associated myelopathy/tropical spastic paraparesis from a Brazilian cohort: ROC curve analysis to establish the threshold for risk disease.

Human T-lymphotropic virus 1 (HTLV-1) infection is associated with HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which affects approximately 5% of carriers. High proviral load is a risk marker for HAM/TSP, although there is an overlap of proviral load levels in peripheral blood between asymptomatic carriers and HAM/TSP patients. In this study, receiver operating characteristic curve analysis was used to define a set point of HTLV-1 proviral load that better indicates an increased risk for HAM/TSP. Proviral load was quantified in 75 asymptomatic carriers and 78 HAM/TSP patients in a Brazilian cohort. The cut-off of proviral load was defined as 114 copies/10(4) cells, with 78.2% sensitivity to identify true HAM/TSP patients. The mean proviral load levels were not significantly different between males and females with the same clinical status, and there was no significant correlation between proviral load and age at blood sampling, age at the onset of illness, or duration of disease. In HAM/TSP patients, proviral load was significantly higher in wheelchair-bound patients than in individuals able to walk without support and in those with the worst spinal cord injuries. Follow-up of HTLV-1-infected individuals showed that proviral load was more stable in asymptomatic carriers than in HAM/TSP patients. In a cohort study, periodically quantifying proviral load in asymptomatic carriers is necessary to identify those at risk for developing neurological disease, and it is necessary for HAM/TSP patients to monitor spinal injury and progression to walking disability. The measure of proviral load in clinical practice implicates the definition of the cut-off of proviral load and its validation during follow-up.