Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia/lymphoma in a Black population.
BACKGROUND
Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM; also known as tropical spastic paraparesis [TSP]), a chronic neurodegenerative disorder. Worldwide, several million HTLV-I carriers are at risk for disease, with an estimated lifetime cumulative risk of 1%-5%. However, the determinants of disease progression are relatively unknown. We studied human leukocyte antigens (HLA class II) that have been implicated in the pathogenesis of HTLV-I-related diseases.


METHODS
We analyzed HLA class II alleles among asymptomatic HTLV-I carriers (n = 45), patients with ATL (n = 49) or HAM/TSP (n = 54), and HTLV-I seronegative control subjects (n = 51). All participants were of African descent and were enrolled in epidemiologic studies conducted at the University of the West Indies, Kingston, Jamaica. We used standard microlymphocytotoxicity assays for HLA antigen serotyping and polymerase chain reaction-based methods to examine HLA class II DRB1 and DQB1 alleles.


RESULTS
Two antigens determined by serotyping, DR15 and DQ1, occurred at significantly increased frequency among HTLV-I carriers compared with seronegative control subjects (42% versus 22% for DR15 [odds ratio [OR] = 2.7; 95% confidence interval [CI] = 1.0-7.2] and 78% versus 53% for DQ1 [OR = 3.1; 95% CI = 1.2-8.5]). Asymptomatic carriers were shown to have an HLA class II allele distribution similar to that of patients with ATL, and the frequencies of the alleles DRB1*1501, DRB1*1101, and DQB1*0602 were significantly greater in patients with ATL and asymptomatic carriers than in patients with HAM/TSP. In addition, haplotypes DRB1*1101-DQB1*0301 and DRB1*1501-DQB1*0602 were significantly increased among patients with ATL compared with patients with HAM/TSP.


CONCLUSIONS
These data suggest that host genetic background is an important factor in determining whether HTLV-I carriers develop either ATL or HAM/TSP.
Manns
A
A
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA.
Hanchard
B
B
Morgan
O S
OS
Wilks
R
R
Cranston
B
B
Nam
J M
JM
Blank
M
M
Kuwayama
M
M
Yashiki
S
S
Fujiyoshi
T
T
Blattner
W
W
Sonoda
S
S
D000483:Alleles; D044383:Black People / Q000235:genetics*; D002353:Carrier State / Q000821:virology*; D005802:Genes, MHC Class II / Q000235:genetics*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics*; D016017:Odds Ratio