Avaliação longitudinal dos anticorpos anti-tax em indivíduos asssintomáticos e aintomáticos portadores do HTLV-1

Abstract

Human T-lymphotropic virus 1 (HTLV-1) infection is associated with HTLV- Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), which affects approximately 5% of carriers. Despite the pathogenesis of HAM/TSP not being fully elucidated, the proteins Tax and HBZ play an important role in the process by inducing cell proliferation and affecting the response of cytotoxic T lymphocytes. Anti- Tax antibodies are associated with the risk of transmission and development of neoplastic pathologies, with few studies showing an association of these antibodies with other comorbidities. Thus, the present study aimed to evaluate the IgG, IgG1, and IgM anti-Tax response in the serum of HTLV-1 carriers. Samples were obtained from blood donor candidates diagnosed and monitored by the multidisciplinary team of the GIPH cohort (HTLV Interdisciplinary HTLV Research Group), including asymptomatic carriers (AS, n=78), those diagnosed with HAM/TSP during the study – incident HAM (iHAM, n=6), or enrolled in the study with established HAM/TSP (n=10). Three indirect ELISAs were developed to assess each antibody using the C- terminal portion of Tax expressed in a prokaryotic vector as the antigen. The IgG, IgG1 and IgM anti-Tax response was observed in 52.56% / 44.87% / 43.58% of AS carriers; 100%, 83.3% / 83.3% of iHAM patients and 90% / 80% / 80% of HAM/TSP patients, respectively. With regard to anti-Tax reactivity, there was a statistically significant difference between AS and HAM/TSP (p=0.002, p=0.016 and p=0.024) for IgG, IgG1 and IgM, respectively. However, only IgG showed a difference between the AS group and asymptomatic iHAM and those with established HAM/TSP (p= 0.005 and p=0.006, respectively). There was an association between anti-Tax reactivity measured by IgG, IgG1 and IgM with female gender (p=0.012, p=0.017 and p=0.019, respectively) and IgG with proviral load (p=0.025), but not with patient age. The level of the antibodies evaluated remained stable throughout follow-up, being higher in the HAM/TSP and iHAM group than in asymptomatic carriers, with a low intra-individual coefficient of variation. When evaluating AS alone, no relationship was found between the frequency of symptoms and anti-Tax reactivity for the three immunoglobulins. It is noteworthy that in women, the presence of signs and symptoms was higher in those with anti-Tax reactivity compared to those without. Taken together, these data allow us to hypothesize that the humoral response against the Tax protein can be used as a prognostic marker, along with those already classically pointed out, and indicate a relationship between the level of anti-Tax response and the risk of developing HAM/TSP