巴西骨髓增生异常综合征患者的HLA - DRB1和细胞因子多态性及其与红细胞同种免疫的关联。
HLA-DRB1 and cytokine polymorphisms in Brazilian patients with myelodysplastic syndromes and its association with red blood cell alloimmunization.
作者信息
Sirianni Marilia Fernandes Mascarenhas, Sippert Emilia, Blos Bruna, Gonçalves Flavia Ricioli Vaz, Hamerschlak Nelson, Kutner Jose, Castilho Lilian, Marti Luciana Carvalheiro, Bonet-Bub Carolina
机构信息
Departamento de Hemoterapia e Terapia Celular, Hospital Israelita Albert Einstein, São Paulo, Brazil.
Hemocentro, Universidade Estadual de Campinas, Campinas, Brazil.
出版信息
Transfus Med. 2022 Oct;32(5):394-401. doi: 10.1111/tme.12894. Epub 2022 Jul 1.
OBJECTIVE(S): This study aimed investigate association of HLA-DRB1 and cytokine polymorphisms with red blood cell(RBC) alloimmunization in Brazilian Myelodysplastic syndrome(MDS) patients with prior exposure to RBC transfusion.
BACKGROUND
MDS patients are at risk RBC alloimmunization due to chronic RBC transfusion. However, differences in immune response of MDS transfused patients are not completely known.
METHODS/MATERIALS: A retrospective cohort of 87 polytransfused patients with MDS including 28 alloimmunized (PA) and 59 non-alloimmunized (PNA) was evaluated in three Brazilian reference hospitals. HLA-DRB1genotype was performed by polymerase chain reaction (PCR)-SSOP (Luminex platform) and cytokine polymorphisms analysed by PCR and TaqMan assays.
RESULTS
While HLA-DRB1 allele frequencies did not differ between groups, IL17A 197G > A SNP and IL4 polymorphisms showed significant correlation with RBC alloimmunization. IL17A 197A allele A and AA genotype were significantly more frequent in PA than PNA(A, 46.4% versus 27.1%, p = 0.012; OR = 2.3; 95%CI = 1.1-4.9; AA, 25% versus 6.8%, p = 0.041; OR = 6.2; 95%CI 1.3-30.8). Moreover, significant association of alloimmunization to Rh antigens with IL17A 197A allele and AA genotype was also identified in PA group(A, 45% versus 27.1%, p = 0.036; OR = 2.5; 95% CI 1.1-5.7; AA, 30% versus 6.8%, p = 0.042; OR = 7.9; 95%CI 1.5-42.3). Genotype A1A2 of IL4 intron 3 was overrepresented in PA(50% versus 16.9%, p = 0.009; OR = 4.97; 95%CI 1.6-15.5). Similarly, IL4-590 CT genotype was overrepresented in PA(53.6% versus 28.8%, p = 0.049; OR = 3.3; 95%CI 1.2-9.3).
CONCLUSIONS
This study showed no association regarding HLA-DRB1 alleles for RBC alloimmunization risk or protection, however the IL17A 197G>A, IL4 intron 3 and IL4 590C>T SNP was significantly associated to RBC alloimmunization risk in this cohort of Brazilian MDS patients.
目的
本研究旨在调查巴西骨髓增生异常综合征（MDS）患者既往接受红细胞（RBC）输血后，HLA - DRB1和细胞因子多态性与RBC同种免疫之间的关联。
背景
由于长期接受RBC输血，MDS患者存在RBC同种免疫的风险。然而，MDS输血患者免疫反应的差异尚不完全清楚。
方法/材料：在巴西三家参考医院对87例多次输血的MDS患者进行回顾性队列研究，其中包括28例发生同种免疫的患者（PA）和59例未发生同种免疫的患者（PNA）。通过聚合酶链反应（PCR）-SSOP（Luminex平台）检测HLA - DRB1基因型，通过PCR和TaqMan分析检测细胞因子多态性。
结果
虽然两组之间HLA - DRB1等位基因频率没有差异，但IL17A 197G＞A单核苷酸多态性（SNP）和IL4多态性与RBC同种免疫显著相关。PA组中IL17A 197A等位基因A和AA基因型的频率显著高于PNA组（A，46.4%对27.1%，p = 0.012；OR = 2.3；95%CI = 1.1 - 4.9；AA，25%对6.8%，p = 0.041；OR = 6.2；95%CI 1.3 - 30.8）。此外，在PA组中还发现同种免疫与Rh抗原和IL17A 197A等位基因及AA基因型之间存在显著关联（A，45%对27.1%，p = 0.036；OR = 2.5；95%CI 1.1 - 5.7；AA，30%对6.8%，p = 0.042；OR = 7.9；95%CI 1.5 - 42.3）。PA组中IL4内含子3的A1A2基因型比例过高（50%对16.9%，p = 0.009；OR = 4.97；95%CI 1.6 - 15.5）。同样，PA组中IL-4 - 590 CT基因型比例过高（53.6%对28.8%，p = 0.049；OR = 3.3；95%CI 1.2 - 9.3）。
结论
本研究表明，HLA - DRB1等位基因与RBC同种免疫风险或保护无关联，然而在这组巴西MDS患者中，IL17A 197G＞A、IL4内含子3和IL4 590C＞T SNP与RBC同种免疫风险显著相关。
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