Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population.

Around ten million people are infected with HTLV-1 worldwide, and 1-4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy-Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions.

Human Leukocyte Antigens class II (HLA II) gene profile from an admixed population of patients with type 1 diabetes with severe diabetic retinopathy: a nested case-control study in Brazil.

BACKGROUND: Although the well-established role of the HLA genes on the predisposition of type 1 diabetes (T1D), its contribution to the development and progression of diabetic retinopathy is still unclear, especially in admixed populations. We aimed to study the relationship between HLA alleles and severe diabetic retinopathy in a highly admixed population of T1D patients. METHODS: This was a nested case-control study based on a cross-sectional, nationwide survey conducted in Brazil. We included 117 patients with severe diabetic retinopathy and 117 random controls composed of T1D patients without retinopathy, matched for diabetes duration. HLA-class II genes (HLA-DRB1, -DQA1, and -DQB1) were genotyped using the SSO and NGS methods. RESULTS: Haplotypes HLA-DRB1*04:05 ~ DQA1*03:01 g ~ DQB1*03:02 (OR 1.75, CI 0.97-3.16, p value 0.058) and HLA-DRB1*13:02 ~ DQA1*01:02 ~ DQB1*06:04 (OR 5.18, CI 1.12-23.09, p value 0.019) were more prevalent on the severe DR group but they did not present statistically difference after Bonferroni correction. The most frequent haplotype on both groups was HLA-DRB1*03:01 ~ DQA1*05:01 g ~ DQB1*02:01 (29.6% on severe DR and 33.33% on the control group). CONCLUSIONS: Our study showed no influence of HLA genes on the development of DR. Further longitudinal data is needed to better understand the role of genetic factors on this multifactorial significant microvascular complication.