HLA-B*35 as a new marker for susceptibility to Human T-cell Lymphotropic Virus type 1 (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in patients living in Argentina
Abstract Background: Human T 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 72 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.Results: The frequency of HLA-A, -B and -C alleles largely matched that of the general population in Argentina. We identified HLA-A*02 and HLA-B*35 as associated to protection from ATLL (p=0.037) and susceptibility to HAM/TSP (p<0.001), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p=0.003), but were unable to identify any particular allele associated with high or low PVL.Conclusions: Our results match several previous reports that link HLA-A*02 and protection from disease. However, this is the first study associating HLA-B*35 to susceptibility to disease in HTLV-1, an allele that has been largely associated to different severity factors related to other viral infections, such as Human Immunodeficiency Virus (HIV-1) and Hepatitis B Virus (HBV).