Abstract
BackgroundHuman T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2–5% of the infected individuals. Host genetic background might play a role in disease progression. Several previous studies across many countries report HLA haplotype to be one such factor. Here, we sequenced HLA-A, -B and -C of 66 individuals by Sequence-Based Typing (SBT), and compared the frequency of different alleles among ATLL patients, HAM/TSP patients, asymptomatic carriers and non-infected individuals living in Argentina.ResultsThe frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02, HLA-B*35 and HLA-C*07 as associated to protection from ATLL (p = 0.031), susceptibility to HAM/TSP (p < 0.001) and susceptibility to ATLL (p = 0.017), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p = 0.008), but were unable to identify any particular allele associated with high or low PVL.ConclusionsWe have found HLA-A*02, HLA-B*35 and HLA-C*07 to be associated to protection from ATLL (HLA-A*02) and susceptibility to HAM/TSP (HLA-B*35) or to ATLL (HLA-C*07), respectively. Whereas HLA-A*02 protection from ATLL has already been extensively described in other regions of the world, this is the first report that links HLA-B*35 and an increased susceptibility to HAM/TSP. As for HLA-C*07 it has previously been associated to susceptibility to HAM/TSP in other countries but in our population it has been linked to ATLL.
Highlights
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2–5% of the infected individuals
There was a significant difference in age (p = 0.002, mean age = 41.05, mean age non-infected individuals (NII) = 32.27, mean age asymptomatic carriers (AC) = 38.6, mean age HAM/TSP = 46.57, mean age ATLL = 44.33, Table 2) when analyzing the same groups
Out of the 66 samples included in the study, a total of 53 were typed for Human Leukocyte Antigen (HLA)-A (13 NII, 17 AC, 7 ATLL, 16 HAM/TSP), 61 for HLA-B (14 NII, 19 AC, 7 ATLL, 21 HAM/TSP) and 38 of them were analyzed for HLA-C (14 NII, 18 AC, 3 ATLL, 3 HAM/TSP)
Summary
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of HTLV associated myelopathy/ Tropical Spastic Paraparesis (HAM/TSP) and Adult T cell leukemia/lymphoma (ATLL), in around 2–5% of the infected individuals. Human T-cell lymphotropic virus type 1 (HTLV-1) was the first human retrovirus to be discovered and is the etiological agent of Adult T Cell Leukemia/Lymphoma (ATLL), a progressive neurological disease called HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) [1, 2], Uveitis, a severity factor for Bronchiectasis and other diseases [3]. The increased number of HTLV-1 infected T-cells may cause imbalance of the immune system, resulting in immune dysfunction or inflammatory diseases like myelopathy and uveitis [9] In this context, HAM/TSP pathogenesis is a hyperactive immune response induced by HTLV-1 infection that produces chronic inflammation in the central nervous system (CNS) with slowly progressive evolution. It is characterized by the production of elevated levels of proinflammatory cytokines, including IFN-ɣ and TNF, and by HTLV-1-specific CD8+ T cells in peripheral blood and spinal cord lesions [10,11,12]
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