Cytokine profile and proviral load among Japanese immigrants and non-Japanese infected with HTLV-1 in a non-endemic area of Brazil

• Published in: PloS one 2017-04, Vol.12 (4), p.e0174869-e0174869
• Main Authors: Domingos, João Américo, Soares, Luana Silva, Bandeira, Larissa M, Bonin, Camila Mareti, Vicente, Ana C P, Zanella, Louise, Puga, Marco Antonio Moreira, Tozetti, Inês Aparecida, Motta-Castro, Ana Rita Coimbra, da Cunha, Rivaldo Venâncio
• Format: Article
• Language: English
• Subjects: Aged; Asian Continental Ancestry Group; Biology and life sciences; Brazil - epidemiology; Care and treatment; Carrier State - epidemiology; Carrier State - immunology; Carrier State - virology; Carriers; Case-Control Studies; Central nervous system diseases; Cohort Studies; Correlation; Cytokines; Cytokines - blood; Emigrants and Immigrants; Etiology (Medicine); Female; Gene expression; Hereditary spastic paraplegia; HTLV-I (Virus); HTLV-I Infections - epidemiology; HTLV-I Infections - immunology; HTLV-I Infections - virology; Human T-lymphotropic virus 1 - isolation & purification; Human T-lymphotropic virus 1 - pathogenicity; Humans; Immigrants; Immune status; Immunology; Infections; Interleukin 1; Interleukin 10; Interleukin 17; Interleukin 2; Interleukin 4; Interleukin 6; Japan - ethnology; Low frequencies; Male; Medicine and Health Sciences; Middle Aged; Minority & ethnic groups; Noncitizens; Paraparesis, Tropical Spastic - epidemiology; Paraparesis, Tropical Spastic - immunology; Paraparesis, Tropical Spastic - virology; Pathogenesis; Patients; People and places; Polymerase chain reaction; Prospective Studies; Proviruses - isolation & purification; Research and Analysis Methods; Serum levels; Spastic paraparesis; Spinal cord; Studies; Syphilis; Tropical spastic paraparesis; Tumor necrosis factor; Tumor necrosis factor-TNF; Viral Load; γ-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0174869

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.