HLA-DRB1和细胞因子多态性在巴西骨髓增生异常综合征患者及其与红细胞异体免疫的关系

Transfusion Medicine (Oxford, England) Pub Date : 2022-10-01 Epub Date: 2022-07-01 DOI:10.1111/tme.12894
Marilia Fernandes Mascarenhas Sirianni, Emilia Sippert, Bruna Blos, Flavia Ricioli Vaz Gonçalves, Nelson Hamerschlak, Jose Kutner, Lilian Castilho, Luciana Carvalheiro Marti, Carolina Bonet-Bub
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引用次数: 1

摘要

目的:本研究旨在探讨HLA-DRB1和细胞因子多态性与巴西骨髓增生异常综合征(MDS)患者红细胞异体免疫的关系。背景:MDS患者由于长期输血存在红细胞异体免疫风险。然而,MDS输血患者的免疫应答差异尚不完全清楚。方法/材料:对巴西三家参考医院87例多次输血MDS患者进行回顾性队列研究,其中28例同种异体免疫(PA)和59例非同种异体免疫(PNA)。采用聚合酶链反应(PCR)-SSOP (Luminex平台)进行hla - drb1基因分型,采用PCR和TaqMan法分析细胞因子多态性。结果:HLA-DRB1等位基因频率在组间无差异,IL17A 197G > A SNP和IL4多态性与RBC同种异体免疫有显著相关性。il17a197a等位基因A和AA基因型在PA中的出现频率显著高于PNA(A, 46.4%比27.1%,p = 0.012;或= 2.3;95%ci = 1.1-4.9;AA, 25%对6.8%,p = 0.041;或= 6.2;95%可信区间1.3 - -30.8)。此外,在PA组中,对Rh抗原的同种免疫与il17a197a等位基因和AA基因型也有显著的相关性(A, 45%对27.1%,p = 0.036;或= 2.5;95% ci 1.1-5.7;AA, 30%对6.8%,p = 0.042;或= 7.9;95%可信区间1.5 - -42.3)。IL4内含子3的A1A2基因型在PA中被过度代表(50%比16.9%,p = 0.009;or = 4.97;95%可信区间1.6 - -15.5)。同样,IL4-590 CT基因型在PA中被过度代表(53.6%比28.8%,p = 0.049;或= 3.3;95%可信区间1.2 - -9.3)。结论:本研究显示HLA-DRB1等位基因与红细胞异体免疫风险或保护没有关联,但IL17A 197G>A、IL4含子3和IL4 590C>T SNP与巴西MDS患者的红细胞异体免疫风险显著相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
HLA-DRB1 and cytokine polymorphisms in Brazilian patients with myelodysplastic syndromes and its association with red blood cell alloimmunization.

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.

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