Abstract
The lifetime risk of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) development differs among ethnic groups. To better understand these differences, this prospective cohort study was conducted to investigate the cytokine profile and the HTLV-1 proviral load (PVL) in Japanese and non-Japanese populations with HAM/TSP and asymptomatic carriers (ACs). The serum IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, and IFN-γ levels were quantified using the Cytometric Bead Array in 40 HTLV-1-infected patients (11 HAM/TSP and 29 ACs) and 18 healthy controls (HCs) in Brazil. Among ACs, 15 were Japanese descendants and 14 were non-Japanese. Of 11 patients with HAM/TSP, only one was a Japanese descendant. The HTLV-1 PVL was quantified by real-time PCR. The HTLV-1 PVL was 2.7-fold higher in HAM/TSP patients than ACs. Regardless of the clinical outcome, the PVL was significantly higher in patients younger than 60 years than older patients. The HAM/TSP and ACs had higher IL-10 serum concentrations than that of HCs. The ACs also showed higher IL-6 serum levels than those of HCs. According to age, the IL-10 and IL-6 levels were higher in ACs non-Japanese patients older than 60 years. HAM/TSP patients showed a positive correlation between IL-6 and IL-17 and a negative correlation between the PVL and IL-17 and IFN-γ. In the all ACs, a significant positive correlation was observed between IL-2 and IL-17 and a negative correlation was detected between IL-10 and TNF-α. Only 6.25% of the Japanese patients were symptomatic carriers, compared with 41.67% of the non-Japanese patients. In conclusion, this study showed that high levels of HTLV-1 PVL was intrinsicaly associated with the development of HAM/TSP. A higher HTLV-1 PVL and IL10 levels found in non-Japanese ACs over 60 years old, which compared with the Japanese group depicts that the ethnic background may interfere in the host immune status. More researches also need to be undertaken regarding the host genetic background to better understand the low frequency of HAM/TSP in Japanese HTLV-1-infected individuals.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma [1]
The study population was classified into 3 groups: healthy controls (n = 18), HTLV-1-infected asymptomatic carriers (n = 29), and HAM/TSP patients (n = 11)
There were no significant differences in demographic characteristics, i.e., age and gender, among HTLV-1-infected asymptomatic carriers, HAM/TSP patients, and healthy controls (Table 1), revealing homogeneity between the 3 groups
Summary
Human T-lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma [1]. The lifetime risks of developing ATLL and HAM/TSP are estimated to be 2.5–5% and 0.3–2%, respectively, whereas most HTLV-1-infected individuals remain lifelong asymptomatic carriers (ACs) [2]. Other HTLV-1-associated inflammatory diseases, including uveitis, sicca syndrome, polyarthralgia, and infective dermatitis, result from immune dysfunctions caused by this virus [3,4,5,6,7]. Despite the wide geographic distribution of HTLV-1, the prevalence varies extensively according to geographical area [8]. Southwestern Japan, the Caribbean islands, Central and South America, sub-Saharan Africa, Melanesia, and the Middle East are considered endemic areas of HTLV-1 infection [9,10]. Brazil has the highest absolute number of HTLV-1/2infected individuals in the world, and we previously reported that HTLV-1 infection is prevalent (6.8%) among the Japanese community in the Midwestern region of Brazil [11,12,13]
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