Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease.
Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease.
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HLA-DQB1等位基因对镰状细胞疾病患者的保护作用。
DOI：
10.1016/j.humimm.2015.10.010
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发表时间：
2016-01
期刊：
影响因子：
2.7
通讯作者：
Tamouza R
中科院分区：
文献类型：
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作者：
Tatari-Calderone Z;Gordish-Dressman H;Fasano R;Riggs M;Fortier C;Campbell AD;Charron D;Gordeuk VR;Luban NLC;Vukmanovic S;Tamouza R
同种免疫或红细胞（RBC）抗原的同种抗体的发展被认为是镰状细胞病（SCD）患者输注RBC后的主要并发症之一，可导致急性和迟发性溶血反应。HLA基因多态性可能在同种异体免疫中起作用。我们进行了一项回顾性研究，分析HLA-DRB 1和DQB 1基因多样性对RBC同种免疫的影响。采用IMGT HLA数据库，通过PCR-SSO对204例有或无RBC同种异体免疫的多次输血SCD患者进行低/中分辨率分型。使用逻辑回归模型分析HLA-DRB 1和DQB 1等位基因频率，并使用多元逻辑回归计算总体p值。虽然仅观察到HLA-DR多样性与同种免疫之间的关联趋势，但HLA-DQ的分析显示，HLA-DQ 2（p=0.02）、-DQ 3（p=0.02）和-DQ 5（p=0.01）等位基因在非同种免疫患者中显著更高，可能表现为保护性等位基因。此外，多元逻辑回归分析显示HLA-DQ 2/6（p=0.01）和HLA-DQ 5/5（p=0.03）组合构成保护状态的额外预测因子。我们的数据表明，特定的HLA-DQ等位基因影响SCD患者红细胞输注的临床过程，这可能为预测策略铺平道路。
Alloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization. Two-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT-HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression. While only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p=0.02), -DQ3 (p=0.02) and -DQ5 (p=0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p=0.01) and HLA-DQ5/5 (p=0.03) combinations constitute additional predictor of protective status. Our data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.