Association between HLA alleles and HAM/TSP in individuals infected with HTLV-1

Abstract

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) develops in less than 5 % of HTLV-1 carriers. It is unclear which factors trigger the development of disease. The aim of this study was to explore the influence of HLA alleles on the development of HAM/TSP. A total of 40 HTLV-1-infected individuals belonging to the Spanish HTLV-1 cohort were examined. HTLV-1 proviral load was measured by real-time polymerase chain reaction. HLA class I (A, B, C) and class II (DRB1, DQB1) alleles were genotyped using the bead array technology. Median HTLV-1 proviral load in 12 HAM/TSP patients was greater than in 28 asymptomatic carriers (637 vs. 71 copies per 10(4) peripheral blood mononuclear cells; p = 0.006). Moreover, HAM/TSP was significantly associated with HLA-B 07 and HLA-DRB1 01:01 (p = 0.039). Interestingly, individuals with these HLA alleles had greater HTLV-1 proviral load than asymptomatic carriers (p = 0.036). In summary, HLA testing should be considered in asymptomatic HTLV-1 individuals and close monitoring of HTLV-1 proviral load along with periodic neurological evaluations should be prioritized in HLA-DRB1 01:01 and HLA-B 07 carriers.

Genetic Markers of the Host in Persons Living with HTLV-1, HIV and HCV Infections

“…There may be differences in the frequency of HLA alleles in different populations, and changes in the protective effect of certain HLA alleles according to ethnicity ( Table 1 ). The same protective effect of HLA-A*02 in HAM/TSP, seen in Japanese, has been reported in a small sample of 29 individuals from London, 27 of whom had a Caribbean origin [ 2 ], a finding also observed in Brazil [ 5 , 6 ] but not in other populations, such as Afro-Caribbean individuals from Martinique [ 7 ], Jamaica [ 8 ], Spain [ 9 ] and Iran [ 10 , 11 ].…”

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

“…Some studies have proposed that HLA allelic variants could determine the PVL levels of HTLV-1 infected individuals (14,49). Nonetheless, we couldn't nd any signi cant differences in the PVL of any allele to support these previous claims (Table 4).…”

Human T‐lymphotropic virus 1 (HTLV‐1)‐associated lichenoid dermatitis induced by CD8+ T cells in HTLV‐1 carrier, HTLV‐1‐associated myelopathy/tropical spastic paraparesis and adult T‐cell leukemia/lymphoma

“…The feasibility of occurrence of CTL autoimmune responses to HTLV‐1 tax‐related peptides depends on HLA haplotypes . Furthermore, the cytotoxic activity is influenced by the activity of CTL and the regulatory role of neoplastic cells or Treg.…”

“…2 The apparent conversion of the condition to overt ATLL is inhibited in HAM/ TSP and uveitis, 2,23 and the patients are initially recognized as HTLV-1 carriers. HAM/TSP prefers certain HLA class I haplotypes, which present an antigenic HTLV-1 tax peptide to cytotoxic T cells (CTL), 23,24 leading to the non-leukemic state.…”

“…The feasibility of occurrence of CTL autoimmune responses to HTLV-1 tax-related peptides depends on HLA haplotypes. 23,24 Furthermore, the cytotoxic activity is influenced by the activity of CTL and the regulatory role of neoplastic cells or Treg. In HTLV-1-infected individuals, CTL are exhausted with high expression of programmed death-1 (PD-1), suggesting the PD-1/PD-L1 pathway plays a role in fostering persistent HTLV-1 infections.…”