Prognosis Markers for Monitoring HTLV-1 Neurologic Disease

Abstract

Background:HTLV-1 infection is associated not only with some severe manifestations, such as HAM and ATLL, but also with other, less severe conditions. Some studies have reported neurological manifestations who did not meet all the criteria for the diagnosis of HAM in individuals infected with HTLV-1, these conditions may later progress to HAM or constitute an intermediate clinical form, between asymptomatic HTLV-1 carriers and those with full myelopathy. This study evaluated the prognostic value and looked for a possible association of those parameters with the Intermediate Syndrome (IS) status and HAM status.Methods:Proviral load, spontaneous lymphoproliferation, IFN-γ spontaneous production was quantified in samples of asymptomatic and HAM patients, as well as patients with IS.Results:50-60 years was critical age range for SI outcome and more of 60 years old for HAM outcome with increased risk of 2.5 fold for IS and 6.8 fold for HAM. IFN-γ was increased in IS patients compared with AC (p=0.007) and in HAM patients compared with AC (p=0.03). Lymphoproliferation was increased in HAM vs AC (p=0.0001) and IS patients (p=0.0001). Proviral load was similar between groups.Conclusion:IFN-γ has high specificity of prediction of subject remain asymptomatic compared with PVL and LPA tests. IFN-γ has been shown to be a biomarker of progression to intermediate stage and to HAM. The association of other markers with manifestations associated with HTLV-1 infection that does not meet the HAM criteria should be verified.

Case Report: Relevance of an Accurate Diagnosis and Monitoring of Infective Dermatitis Associated With Human T-Lymphotropic Virus Type 1 in Childhood

“…HTLV-1 infection induces cytokine and chemokine deregulation. Increased concentrations of IL-1β, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), CXCL10 and IFN-γ have been reported in HAM/TSP cerebrospinal fluid, and recently, an increased concentrations of IFN-γ in plasma have been reported to be a biomarker of progression to the intermediate syndrome status and HAM/TSP ( 23 ). In this patient, IL-6 and IL-9 were elevated in plasma, but not IFN-γ, which suggests that risk of HAM/TSP is not yet present.…”

The role of IFN-γ production during retroviral infections: an important cytokine involved in chronic inflammation and pathogenesis

“…The production of IFN-gamma by CD8+ T cells is considerable in the central nervous system (CNS) due to the volume of cells expressing MHC class I antigens; it is also related to MHC class II involved in the production of IFN-γ 6 , 20 . Therefore, the spontaneous IFN-γ production is more likely due to TAX activation over certain genes in the hosted cells 14 , 21 ( Figure 1 ).…”

“…Different immunological aspects are involved in virus/host interaction, and the way this interaction develops will determine whether the patient will be asymptomatic or afflicted with some condition, such as HAM 20 . In this sense, IFN can be a potential marker to predict early disease development, since HAM is an immune-mediated disease, and may be of greater prognostic value when compared to HTLV-1 proviral load 14 . The immune response during viral infection is one of the important parameters that can determine the degree of infection.…”

“…The production of IFN-gamma by CD8+ T cells is considerable in the central nervous system (CNS) due to the volume of cells expressing MHC class I antigens; it is also related to MHC class II involved in the production of IFN-γ 6,20 . Therefore, the spontaneous IFN-γ production is more likely due to TAX activation over certain genes in the hosted cells 14,21 (Figure 1). Some genes are over-expressed in the white blood cells of patients with HAM (HTLV-1-associated myelopathy), but not in asymptomatic HTLV-1 carriers or patients with the disease clinically similar to multiple sclerosis 22,23 .…”

“…There is a lack of this regulatory mechanism and constant influence of the IL-2 8 , 12 and no limitation of the intensity of inflammatory response 8 , 13 . IFN-γ and IL-2 play a crucial role in the replication of host cells and may be a biomarker to monitor disease progression in infections 6 , 14 . This chronic overexpression of IFN-γ in different tissues can initiate several inflammatory disorders and excessive damage to tissues.…”