Abstract
HTLV-1 infections are persistent and frequently latent; however, productive infections trigger different types of immunological responses that utilize cytokines to control infection. The present study investigated the role of IFNG +874A/T polymorphisms among 153 HTLV-1-infected individuals (33 clinically diagnosed with TSP/HAM, 22 with rheumatologic manifestations, 2 with dermatitis, 1 with uveitis, and 95 asymptomatic patients) and 300 healthy control individuals. Genotyping and proviral HTLV-1 load assessment were performed using real-time PCR assays, and the plasma levels of IFN-γ were measured using an enzyme immunoassay (ELISA). Genotype frequencies were not significantly different, but the presence of the T allele was higher (p < 0.0142) among the asymptomatic patients. Plasma levels of IFN-γ were significantly higher (p < 0.0137) among those with the TT genotype. Their proviral load was also higher, although this elevation did not reach statistical significance. There was no difference in the IFN-γ plasma levels among the symptomatic patients, even when ranked according to disease severity (TSP/HAM or rheumatologic manifestations). However, the difference among asymptomatic patients with the T allele was significantly higher (p < 0.0016) and similar to the plasma levels observed among symptomatic individuals. These results suggest that the IFNG +874A/T polymorphism may modulate the plasma levels of IFN-γ during HTLV-1 infection. Asymptomatic carriers of the polymorphic genotypes appear to develop an inflammatory response in a shorter timeframe, triggering progression to HTLV-1-related symptoms and disorders. These results further suggest that HTLV-1-infected asymptomatic individuals expressing the IFNG +874A/T polymorphism should be monitored more closely in order to readily detect the increase in clinical symptoms, as these patients are potentially at risk of a poor prognosis and should therefore start available treatment procedures earlier.
Highlights
Human T-cell lymphotropic virus type 1 (HTLV-1) infects approximately 5–10 million people worldwide (Cassar and Gessain, 2017)
Most HTLV-1 infections are asymptomatic; under certain conditions not yet fully understood, the virus may lead to the development of associated diseases, including HTLV-1associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T-cell leukemia/lymphoma (ATLL), and inflammatory syndromes such as rheumatoid arthritis, dermatitis, and uveitis (Yakova et al, 2005; Okajima et al, 2013; Quaresma et al, 2015)
This study examined 153 HTLV-1-infected individuals (33 clinically diagnosed with HAM/TSP, 22 with rheumatic manifestations, 2 with dermatitis, 1 with uveitis, and 95 asymptomatic individuals) of both sexes, older than 18 years, not currently being treated with glucocorticoids, who were followed in the outpatient clinic of the Tropical Medicine Division of the Federal University of Pará
Summary
Human T-cell lymphotropic virus type 1 (HTLV-1) infects approximately 5–10 million people worldwide (Cassar and Gessain, 2017). Most HTLV-1 infections are asymptomatic; under certain conditions not yet fully understood, the virus may lead to the development of associated diseases, including HTLV-1associated myelopathy/tropical spastic paraparesis (HAM/TSP), adult T-cell leukemia/lymphoma (ATLL), and inflammatory syndromes such as rheumatoid arthritis, dermatitis, and uveitis (Yakova et al, 2005; Okajima et al, 2013; Quaresma et al, 2015). The development of symptoms, those of HAM/TSP and rheumatoid arthritis, are associated with a high proviral load in the peripheral blood and dysregulation of the immunological response against the virus (Grassi et al, 2011; Coutinho et al, 2014; da Silva Dias et al, 2016). The increases in the numbers of these cells may lead to the development of a hyperimmune response and the marked production of proinflammatory cytokines, contributing to the pathogenesis of inflammatory disorders associated with HTLV-1 (Montanheiro et al, 2009; Yamano et al, 2009)
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