Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy / tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil

Doris Schor,Maria Gloria Bonecini-Almeida,Eric Henrique Roma,Marcel De Souza Borges Quintana,Gustavo Milson Fabricio-Silva,Luís Cristóvão Porto,Maria Jose Andrada-Serpa,Abelardo Queiroz-Campos Araújo

doi:10.1186/s12879-018-3510-1

Doris Schor, Maria Gloria Bonecini-Almeida + Show 6 more

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https://doi.org/10.1186/s12879-018-3510-1

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Abstract

BackgroundHTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce.MethodsThe genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated.ResultsLack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers.ConclusionsWe did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms.

Highlights

Human T-lymphotropic virus 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection
The HTLV-1 virus is the etiological agent of two major diseases: adult T cell leukemia and the neurological disease HTLV-associated myelopathy / tropical spastic paraparesis (HAM/TSP), a progressive neurological and inflammatory disease of the central nervous system
Proviral load was higher in the HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients than Asymptomatic carriers (AC) group(p < 0.04, Table 1)

Summary

Introduction

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. Many of the infected individuals are asymptomatic, approximately 2–5% of the infected individuals will develop HAM/TSP [1] This neurological disease could be the consequence of an inflammatory network that results in damage of the spinal cord [2], but this association is still poorly understood. The IFN-γ secreted by HTLV-1 infected CD4+T cells and the virus recognition by CD8+T lymphocytes in the central nervous system induces production of other cytokines, such as the myelinotoxic TNF-α This event, together with the hemodynamic changes and interactions mediated by adhesion molecules among circulating lymphocytes and endothelial cells, which contribute to the location of spinal cord injury, is known as a “bystander” damage hypothesis. Cerebrospinal fluid levels of cytokines (ITAC, IFN-γ, IL-5, IL-8 and TNF-α) were higher in HAM/TSP compared with AC patients, indicating that those cytokines might be used as disease markers of neurologic manifestation in long-term HTLV-1 infected individuals [7]

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