Genes HLA-A, -B e -DR no transplante alogênico de células tronco hematopoéticas

Abstract

HLA (Human Leucocyte Antigens) molecules are proteins encoded by polymorphic genes and are involved in the regulation of adaptive immune responses. Their polymorphisms are selected by sequences of hypervariable nucleotides that result in two or more different alleles of the same gene. Considering that malignant neoplasms and autoimmune diseases are caused, among other factors, by structural changes in the genome and that immune evasion mechanisms affect the expression and/or function of HLA genes; it is essential to establish relationships between the polymorphisms of this gene and disease susceptibility and resistance. These potential relationships can clarify the contribution of HLA genes as additional factors in pathophysiology and their treatment. Objectives: The general objective of this study was to verify the association between HLA genes and hematological diseases in patients undergoing hematopoietic stem cell transplantation. Material and Method: The allele frequencies for the HLA-A, -B and -DRB1 locus were analyzed in a sample of 221 patients who have undergone allogeneic hematopoietic stem cell transplantation and 200 voluntary bone marrow donors. HLA alleles were identified by the low resolution PCR-rSSO method. The ARLEQUIN software was used to calculate allele frequencies, and Fisher's exact test was used for comparisons between groups (p≤0.05) of patients with acute myeloid leukemia (n = 77), acute lymphoid leukemia (n = 39) and severe aplastic anemia (n = 27). Results: Twenty groups of alleles were identified for the HLA-A locus, 28 for HLA-B and 13 for HLA-DRB1. In the control group, the most frequent alleles for each locus were HLA-A*02, HLA-B*35 and HLA-DRB1*11. Either in the group of patients with acute myeloid leukemia (OR = 0.38; 95% CI 0.21 - 0.68; p = 0.001; pc = 0.022) or in patients with severe aplastic anemia (OR = 0.14; CI 95% 0.02 - 0.54; p = 0.001; pc = 0.011); statistically significant differences were found in the distribution of the HLA-DRB1*11 allele. Conclusion: HLA-DRB1*11 allele can be considered a potential immunogenetic protective factor for the development of acute myeloid leukemia and severe aplastic anemia in the analyzed sample. This suggests that this allele contributes to the adaptive immune response in primary events of the development of neoplasia and autoimmune disease.