Fundação Centro de Hematologia e Hemoterapia de Minas Gerais - Hemominas, Belo Horizonte, Brazil.
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
HLA. 2017 Oct;90(4):211-218. doi: 10.1111/tan.13102. Epub 2017 Aug 11.
Hematopoietic stem-cell transplantation (HSCT) is currently the only established curative treatment for sickle cell disease (SCD), but is limited by donor availability. Ethnicity is thought to have an impact on the complications experienced by patients that undergo HSCT and on the likelihood of identifying an human leukocyte antigen (HLA) matched donor. In the present study, we investigated the genomic ancestry and the distribution of HLA allele groups in Brazilian patients with SCD, compared these HLA profiles to worldwide populations and evaluate the availability of HLA-matched donors. A broad intercontinental admixture of patients with SCD was observed, with African ancestry ranging from 6.7% to 93.4%. In a dendrogram based on HLA frequencies, Brazilian patients with SCD were included in a branch containing only populations with a significant African component. Among the 126 patients evaluated, 10 (8%) found a HLA-matched unrelated donor in a database of 18 134 donors. Self-reported white, brown and black matched donors were identified, and no significant difference in the percentage of compatible donors was observed between these ethnic groups. Our results show that Brazilian patients with SCD are very admixed, indicating that this group is a promising target for admixture mapping of genes involved in complications after HSCT. Additional studies may help to clarify the impact of the genetic diversity and admixture of these patients on the donor availability.
造血干细胞移植（HSCT）是目前治疗镰状细胞病（SCD）的唯一有效方法，但受到供体可用性的限制。种族被认为会影响接受 HSCT 的患者的并发症发生情况以及找到 HLA 匹配供体的可能性。在本研究中，我们调查了巴西 SCD 患者的基因组祖籍和 HLA 等位基因组的分布，将这些 HLA 图谱与世界人群进行比较，并评估 HLA 匹配供体的可用性。观察到 SCD 患者存在广泛的洲际混合，非洲血统比例为 6.7%至 93.4%。在基于 HLA 频率的系统发育树上，巴西 SCD 患者被包含在一个仅包含具有重要非洲成分的人群的分支中。在评估的 126 名患者中，有 10 名（8%）在 18134 名供体的数据库中找到了 HLA 匹配的无关供体。发现了自我报告的白人、棕色和黑人匹配供体，并且在这些族裔群体之间观察到相容供体的比例没有显着差异。我们的结果表明，巴西 SCD 患者的混合程度非常高，这表明该群体是参与 HSCT 后并发症的基因混合映射的有前途的目标。进一步的研究可能有助于阐明这些患者的遗传多样性和混合程度对供体可用性的影响。
