HLA association with HTLV-1/2 infection in different populations of Argentina

BERINI C, EIRIN ME, MALAN R, ESPEJO R, DELFINO C, THEILER G, BIGLIONE M.

Leuven

Conferencia; 15th International Conference on Human Retrovirology: HTLV and related viruses; 2011

The International Retrovirology Association

Introduction: HLA class 1 alleles HLA-A*24,*26 and HLA-B*07,*61 were associated to susceptibility for HTLV-1 infection while HLA-A*02 was associated to protection against development of HAM/TSP. HLA-B*07 was also associated to susceptibility for HAM/TSP development. Alleles HLA-A*02 and HLA-B*27,*40,*48 were described in aboriginal populations of Russia genetically related to Andean aborigines. The aim of this study was to analyze the association of HLA with susceptibility to HTLV-1 or 2 infections. Materials and methods: A total of 118 samples were studied. Of them, 60 negative samples belonged to aboriginal populations of Argentina (15 Kollas, 15 Huarpes, 15 Wichis and 15 Guaraníes). Of the 23 HTLV-1 positive samples, 12 were from blood donors and 11 from Kollas. The 32 HTLV-2 positive samples were from residents of Buenos Aires, predominantly of Caucasian origin. HLA class 1 (A, B) and 2 (DR) characterization was performed on genomic DNA using the PCR-SSO technique and chemiluminescence. Exons 2 and 3 of HLA-A and B genes, and exon 2 of HLA-DR were amplified. Results: For HLA-A nine polymorphisms were observed among negative individuals, 10 in HTLV-1 positive and 16 in HTLV-2 positive individuals. The HLA-A*02 allele was frequently observed in all groups, being significantly higher among HTLV-1 positive compared to HTLV-2 positive and negative individuals, and also significantly higher among HTLV-1 positive Kollas compared to non-infected ones (p=0.03). HLA-A*31 and *68 were significantly more frequent among negative individuals. Regarding HLA-B, only 3 alleles showed significant differences in their frequencies, being HLA-B*07 higher in HTLV-2 positive individuals compared to HTLV-1 and negative individuals; HLA-B*35 higher in HTLV-1 compared to HTLV-2 and also higher among HTLV-1 infected Kollas compared to HTLV-1 infected Caucasians. HLA-B*40 was             higher in negative individuals, especially among Guaraníes, compared to HTLV-2 positive ones. As for HLA-DR (class 2) 14 polymorphisms were detected. HLA-DR*04 frequency was significantly higher among HTLV-2 compared to HTLV-1 and negative individuals. HLA-DR*08 was significantly higher in HTLV-1 positive compared to HTLV-2 positive individuals. On the other hand, for alleles HLA-DR*07, *11 and *13, the frequency was significantly higher in HTLV-2 compared to negative individuals while for allele *14 the frequency was higher among negative individuals compared to HTLV-2 positive ones. Discussion: The presence of HLA-A*02 was higher among Kollas, Guaranìes and HTLV-1 infected individuals in agreement with previous reports (Talledo et al., 2010; Catalán-Soares et al., 2009; Lou et al., 1998). Even though this allele was also found in aboriginal populations of Rusia as well as in these aboriginal populations, it was significantly higher among HTLV-1 infected Kollas suggesting a possible association to susceptibility to infection. It may also have a protective effect against HAM/TSP development as previously reported, as all the infected individuals were asymptomatic and older than the mean age for HAM/TSP presentation. Previous reports have associated the presence of alleles HLA-A*24, *26 to HTLV-1 infected individuals (Sonoda el at, 2005), which although present in our populations no association was detected. The frequency of alleles HLA-A*31 and *68 was higher among negative individuals compared to HTLV-1/2 infected ones. These alleles were present only among negative Kollas when compared to infected ones, suggesting a possible protection against HTLV-1 natural infection. Regarding HLA-B, the alleles *07 and *61 have been previously associated to HTLV-1 infection, fact that was not observed in our population. Moreover, HLA-B*07 was found almost only in HTLV-2 positive individuals suggesting a possible role in HTLV-2 susceptibility to infection, while HLA-B*61 has not been observed in any of the 3 studied populations (Sonoda el at, 2005). HLA-B* 35 was previously described as present in almost all populations, fact that was also reported in this study. Moreover, it was more frequently found among HTLV-1 positive Kollas than Caucasian positives but not in negative Kollas suggesting a possible association to aboriginal ethnic origin (Satz et al., 1995). As for HLA-B*40, it is present in all studied populations with no difference between Caucasians and Aborigines. In contrast to a previous study which reported the presence of HLA-B*14 in HAM/TSP patients, in our population this allele was only observed in Caucasian HTLV-2 and negative aboriginal individuals (Elovaara et al., 1993). On the other hand, HLA-B*54, previously related to HAM/TSP development in Brazil, has not been observed in our HTLV-1 positive population (Catalán-Soares et al., 2009). For HLA-DR most differences were observed between negative and HTLV-2 infected individuals were alleles *04, *07 and *11 were significantly higher in HTLV-2 positive in contrast to alleles *14 and *16 which were more common in negative individuals, especially among Wichis. A high frequency of  A*24, A*02, B*40, B*48 and B*35 was observed in aboriginal populations, in agreement to the results of a previous study conducted in Rusia in a Nivkhi population (Lou et al., 1998). These results clearly show that allele HLA-B*35 is associated to ethnic groups while the presence of alleles HLA-A*02 and HLA-B*07 may increase susceptibility to HTLV-1 and HTLV-2 infection, respectively. Alleles HLA-A*31 and *68 may have a protective effect on HTLV-1 infection while allele HLA-B*35 was present predominantly in aborigines. Therefore, we confirm that susceptibility to HTLV-1/2 infection may be determined by the individual HLA haplotype.