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

Abstract

BackgroundHTLV-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. ObjectivesTo quantify the expression of tax and HBZ mRNA in asymptomatic carriers (AC) and HAM patients, and to investigate their association with HAM/TSP. Study designWe quantified the expression of HTLV-1 tax and HBZ mRNA in 37 AC and 26 HAM patients classified according to proviral load as low (ACL and HAML: <1% infected cells) or high (ACH and HAMH: >1%). ResultsThe ACL subgroup showed the lowest frequency of individuals expressing tax mRNA in comparison with ACH, HAML and HAMH, and tax mRNA load normalized by proviral load was significantly lower in the ACL. 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). ConclusionsThe 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.