Human leukocyte antigen class II alleles associated with human T cell lymphotropic virus type I infection and adult T-vell leukemia/lymphoma in a black population

BACKGROUND: Human T-cell lymphotropic virus type I (HTLV-I) is linked to adult T-cell luekemia/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 percent-5 percent. 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 percent versus 22 percent for DR15 [odds ratio [OR] = 2.7; 95 percent confidence interval [CI] - 1.0-7.2] and 78 percent versus 53 percent for DQ1 [OR = 3.1; 95 percent CI= 1.2-8.5]). Asymptomatic carriers were shown to have and 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 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 weather HTLV-I carriers develop either ATL or HAM/TSP.(AU)

Distribution of HLA and haplotypes of Colombian and Jamaican black populations

To investigate the genetic background of the black populations of Colombia and Jamaica, we determined HLA types of 78 Colombian and 98 Jamaican blacks from 2 different socioeconomic groups (Jamaican #1 and Jamaican #2) and estimated the frequencies of HLA genes and haplotypes. A phylogenetic tree based on the HLA gene frequencies revealed that Jamaican #1 and Jamaican #2 were distinct from each other, Jamaican #1 being closely related to Colombian blacks and the Jamaican #2 being closely related to Senegalese and Zairean populations. Three-locus haplotypes of Colombian and Jamaican #1 blacks were an admixture between Africans and Caucasians or South American Indians while Jamaican #2 blacks were relatively homogeneous and appeared to conserve African lineages. The major five-locus HLA haplotypes were not shared among Colombian, Jamaican #1 and Jamaican #2 blacks. These results indicated that the black populations of Colombia and Jamaica were originated from African blacks and admixed variably with Caucasians and South Americans Indians to make genetic subpopulations in Colombia and Jamaica. (AU)