CD28 Gene Polymorphisms in the Promoter Region Are Associated with Transfusion Reactions: A Functional Study.

Ying-Hao Wen,Wei-Tzu Lin,Ding-Ping Chen,Wei-Ting Wang

doi:10.3390/jcm10040871

Ying-Hao Wen, Wei-Tzu Lin + Show 2 more

Open Access

https://doi.org/10.3390/jcm10040871

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Abstract

Transfusion reactions are mainly induced by the interaction of an antigen and antibody. However, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reaction have been shown, and subjects with certain single nucleotide polymorphisms (SNPs) of the CD28 or CTLA4 gene had a significantly higher risk of transfusion reactions. In total, 40 patients with transfusion reactions after receiving pre-storage leukoreduced blood products were enrolled in this study. We focused on the SNPs located in the CD28 promoter region (rs1879877, rs3181096, rs3181097, and rs3181098) to find out the significant SNP. A luciferase reporter assay was used to investigate the expression level of protein affected by promoter SNP variation. We found that the polymorphism of rs3181097 was associated with transfusion reactions (p = 0.003 in additive model and p = 0.015 in dominant model). Consequently, we investigated the biological function in the CD28 promoter polymorphisms (rs1879877 G > T, rs3181096 C > T, rs3181097 G > A, and rs3181098 G > A) by using dual-spectral luciferase reporter assay. The results showed that the ex-pression level of CD28 was decreased under the effect of rs3181097 with A-allele. This suggested that rs3181097 may regulate immune response through decreasing CD28 protein expression and then lead to development of transfusion reactions.

Highlights

Blood transfusion is a procedure that is used for correcting deficiencies of blood components
We focused on the single nucleotide poly-morphisms (SNPs) located in the CD28 promoter region
There were 40 patients with transfusion reactions after transfusing leukocytepoor red blood cells (LPR) (21 cases) or leukocyte-poor platelets (LPP) (19 cases), and 40 healthy controls were enrolled in the case controlNo

Summary

Introduction

Blood transfusion is a procedure that is used for correcting deficiencies of blood components. They may need blood transfusions because of internal bleeding, cancer cells affecting the kidney or spleen, or bone marrow dysfunction caused by chemotherapy and radiotherapy, which will lead to anemia or shortage of other blood components [1]. Transfusion reaction is an immune response where the compositions of blood products transfused into patients are attacked from the host immune cells [2]. It is more likely to occur in women with multiple pregnancies and persons with repeated transfusions, such as cancer patients [3,4]. Transfusion reaction is mainly induced by the interaction of antigens and antibodies, transfusion reactions still occur with the implementing of crossmatching and usage of pre-storage leukoreduced blood products [5]. The roles of CD28 and CTLA4 gene polymorphisms in transfusion reactions have been shown, and subjects with certain single nucleotide poly-morphisms (SNPs) of CD28 or CTLA4 gene had a significantly higher risk of transfusion reactions [6,7]

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Conclusion