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

Retrovirology. 2020 Sep 3;17(1):29. doi: 10.1186/s12977-020-00536-y.

Abstract

Background: 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. 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.

Results: The 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.

Conclusions: We 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.

Keywords: ARGENTINA; ATLL; HAM/TSP; HLA; HTLV-1; PVL.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles
  • Argentina
  • Disease Progression
  • Female
  • Genetic Association Studies
  • Genetic Markers
  • Genetic Predisposition to Disease / genetics*
  • HLA-A2 Antigen / genetics
  • HLA-B35 Antigen / genetics*
  • HLA-C Antigens / genetics
  • HTLV-I Infections / genetics*
  • HTLV-I Infections / virology
  • Human T-lymphotropic virus 1
  • Humans
  • Leukemia-Lymphoma, Adult T-Cell / genetics
  • Leukemia-Lymphoma, Adult T-Cell / virology
  • Male
  • Middle Aged
  • Paraparesis, Tropical Spastic / genetics*
  • Paraparesis, Tropical Spastic / virology
  • Proviruses / genetics
  • Viral Load
  • Young Adult

Substances

  • Genetic Markers
  • HLA-A2 Antigen
  • HLA-B35 Antigen
  • HLA-C Antigens