Faculty of Medicine of Marília (FAMEMA), Marília, São Paulo, Brazil.
Transfusion. 2014 Oct;54(10):2468-76. doi: 10.1111/trf.12652. Epub 2014 Apr 14.
The Diego blood group presents a major polymorphic site at Residue 854, causing a proline (Di(b) antigen) to leucine (Di(a) antigen) substitution. Di(a) alloimmunization has been observed among Asian and Native South American populations. Considering that Brazilians represent a genetically diverse population, and considering that we have observed a high incidence of Di(a) alloimmunization, we typed HLA-DRB1 alleles in these patients and performed in silico studies to investigate the possible associated mechanisms.
We studied 212 alloimmunized patients, of whom 24 presented immunoglobulin G anti-Di(a) , 15 received Di(a+) red blood cells and were not immunized, and 1008 were healthy donors. HLA typing was performed using commercial kits. In silico analyses were performed using the TEPITOPEpan software to identify Diego-derived anchor peptide binding to HLA-DRB1 molecules. Residue alignment was performed using the IMGT/HLA for amino acid identity and homology analyses.
HLA-DRB107:01 allele was overrepresented in Di(a) -alloimmunized patients compared to nonimmunized patients and to healthy donors. Two motifs were predicted to be potential epitopes for Di(a) alloimmunization, the WVVKSTLAS motif was predicted to bind several HLA-DR molecules, and the FVLILTVPL motif exhibited highest affinity for the HLA-DRB107:01 molecule. Pocket 4 of the DRB1*07:01 molecule contained specific residues not found in other HLA-DRB1 molecules, particularly those at Positions 13(Y), 74(Q), and 78(V).
Individuals carrying the HLA-DRB1*07:01 allele present an increased risk for Di(a) alloimmunization. The identification of susceptible individuals and the knowledge of potential sensitization peptides are relevant approaches for transfusion care, diagnostic purposes, and desensitization therapies.
Diego 血型在 854 位存在一个主要的多态性位点，导致脯氨酸（Di(b)抗原）被亮氨酸（Di(a)抗原）取代。Di(a)同种免疫已在亚洲和南美原住民人群中观察到。考虑到巴西人是一个遗传多样化的群体，并且我们观察到 Di(a)同种免疫的发生率很高，我们对这些患者的 HLA-DRB1 等位基因进行了分型，并进行了计算机模拟研究，以探讨可能的相关机制。
我们研究了 212 名同种免疫患者，其中 24 名患者存在 IgG 抗-Di(a)，15 名患者接受了 Di(a+)红细胞但未发生免疫，1008 名是健康供者。使用商业试剂盒进行 HLA 分型。使用 TEPITOPEpan 软件进行计算机模拟分析，以鉴定 Diego 衍生的锚定肽与 HLA-DRB1 分子的结合。使用 IMGT/HLA 进行残基比对，以进行氨基酸同一性和同源性分析。
与未免疫的患者和健康供者相比，HLA-DRB107:01 等位基因在 Di(a)-同种免疫患者中过度表达。预测到两个基序可能是 Di(a)同种免疫的潜在表位，WVVKSTLAS 基序预测与多个 HLA-DR 分子结合，FVLILTVPL 基序与 HLA-DRB107:01 分子具有最高亲和力。DRB1*07:01 分子的口袋 4 包含特定的残基，这些残基在其他 HLA-DRB1 分子中不存在，特别是位于位置 13（Y）、74（Q）和 78（V）的残基。
携带 HLA-DRB1*07:01 等位基因的个体发生 Di(a)同种免疫的风险增加。鉴定易感个体和了解潜在致敏肽是输血护理、诊断目的和脱敏治疗的重要方法。
