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-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.

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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

10.21203/rs.3.rs-30627/v2 ◽

2020 ◽

Author(s):

Paula Benencio ◽

Sindy A. Fraile Gonzalez ◽

Nicolás Ducasa ◽

Kimberly Page ◽

Carolina A. Berini ◽

...

Keyword(s):

T Cell ◽

Virus Type ◽

Viral Infections ◽

Spastic Paraparesis ◽

Tropical Spastic Paraparesis ◽

T Lymphotropic Virus ◽

Adult T Cell Leukemia ◽

Human T Cell ◽

High Proviral Load

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).

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HLA-B*35 as a new marker for susceptibility to Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) in patients with Human T-cell Lymphotropic Virus type 1 (HTLV-1) in Argentina

10.21203/rs.3.rs-30627/v1 ◽

2020 ◽

Author(s):

Paula Benencio ◽

Sindy A. Fraile Gonzalez ◽

Nicolás Ducasa ◽

Kimberly Page ◽

Carolina A. Berini ◽

...

Keyword(s):

T Cell ◽

Virus Type ◽

Viral Infections ◽

Spastic Paraparesis ◽

Tropical Spastic Paraparesis ◽

T Lymphotropic Virus ◽

Adult T Cell Leukemia ◽

Human T Cell ◽

High Proviral Load

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 73 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 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 = 0.042) and susceptibility to HAM/TSP (p = 0.006), respectively. We also found a strong correlation between high proviral load (PVL) and disease (p = 0.0177), 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).

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Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals

Journal of General Virology ◽

10.1099/vir.0.80509-0 ◽

2005 ◽

Vol 86 (3) ◽

pp. 773-781 ◽

Cited By ~ 42

Author(s):

Amir H. Sabouri ◽

Mineki Saito ◽

Koichiro Usuku ◽

Sepideh Naghibzadeh Bajestan ◽

Mahmoud Mahmoudi ◽

...

Keyword(s):

Risk Factors ◽

T Cell ◽

Virus Type ◽

Spastic Paraparesis ◽

Tropical Spastic Paraparesis ◽

Protective Effects ◽

Provirus Load ◽

Human T Cell ◽

Host Genetic

Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurological disease observed only in 1–2 % of infected individuals. HTLV-1 provirus load, certain HLA alleles and HTLV-1 tax subgroups are reported to be associated with different levels of risk for HAM/TSP in Kagoshima, Japan. Here, it was determined whether these risk factors were also valid for HTLV-1-infected individuals in Mashhad in northeastern Iran, another region of endemic HTLV-1 infection. In Iranian HTLV-1-infected individuals (n=132, 58 HAM/TSP patients and 74 seropositive asymptomatic carriers), although HLA-DRB1*0101 was associated with disease susceptibility in the absence of HLA-A*02 (P=0·038; odds ratio=2·71) as observed in Kagoshima, HLA-A*02 and HLA-Cw*08 had no effect on either the risk of developing HAM/TSP or HTLV-1 provirus load. All Iranian subjects possessed tax subgroup A sequences, and the protective effects of HLA-A*02 were observed only in Kagoshima subjects with tax subgroup B but not in those with tax subgroup A. Both the prevalence of HTLV-1 subgroups and the host genetic background may explain the different risks levels for HAM/TSP development in these two populations.

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