Blood&Genomics

Microchip technology applications for blood group analysis

Hongjun Gao, Gradimir Misevic

2020, 4(2): 83-95. doi: 10.46701/BG.2020022020109

Abstract(290) HTML Full Text (104) PDF(721KB)(18)

Abstract:
Blood group analysis techniques are some of the most in demand immunological applications in clinical transfusion praxis and organ transplantation. In order to aid the advance towards higher throughput and increased sensitivity, analytical solutions dealing with a minimal amount of blood samples and the miniaturization of diagnostic equipment using microchip technologies have been evolving into an optimal solution. Here we review fabrication technologies for various types of microstructure on microchips, related operating procedures, and characterization approaches. Our focus is on examples of microchip technology and instrumentation used for blood group analysis ranging from classical serological methods of glycoprotein detection and solid phase assays, to nucleic acid amplification techniques. Molecular typing using microchip-based techniques is emerging as a supplement to standard serological methods. Microchip technology will play its key role to support blood group analysis at the molecular scale by using microliters of blood samples for extremely sensitive, quantitative, and high throughput analyses.

Coronavirus disease 2019 (COVID-19): diagnosis and prognosis

Xueying Wang, Yang Zhou, Linlin Liu, Jinmin Ma, Honglong Wu, Lijian Zhao, Weijun Chen, Shengwen Calvin Li, Qian Ran, Zhongjun Li

2020, 4(2): 96-107. doi: 10.46701/BG.2020022020120

Abstract(58) HTML Full Text (22) PDF(1361KB)(3)

Abstract:
Coronavirus disease 2019 (COVID-19) has become a global pandemic with a high rate of transmission. Currently, there is a lack of vaccines and specific drugs for this newly-emerged virus. Timely diagnosis and treatment, as well as isolation of patients and virus carriers, contribute to the effective prevention and control of this epidemic. This review focuses on early stage COVID-19 diagnosis methods and strategies, highlighting the guiding role of laboratory indicators on treatment strategy formulation, and prognosis assessments.

Association of the ABO blood group with certain human diseases

Surui Liu, Xiaoya Yang, Gengyin Wang

2020, 4(2): 108-114. doi: 10.46701/BG.2020022020108

Abstract(81) HTML Full Text (17) PDF(258KB)(3)

Abstract:
Following the discovery of ABO blood group over 100 years ago, a variety of studies sought to determine whether different disease states are influenced by ABO inheritance. As oligosaccharide antigens, ABO blood group antigens are widely expressed on the membrane of red blood cells and tissue cells, as well as in the saliva and body fluid. It is by far the most important blood group system in human immunohematology and transfusion medicine. While, other than determining blood group phenotype, accumulating evidence indicates that ABO blood group is implicated in the development of a number of human diseases. This review mainly focuses on the associ-ation between ABO blood group and cardiovascular system risk, corona virus disease 2019 (COVID-19), affective disorders, allergic diseases, as well as cancers.

Overview of the diversity of erythrocyte blood group antigens

Tingting Yang, Zhenqing Feng

2020, 4(2): 115-122. doi: 10.46701/BG.2020022020123

Abstract(97) HTML Full Text (21) PDF(3257KB)(11)

Abstract:
During the differentiation and maturation of erythrocytes, the surface molecules of erythrocytes are gradually expressed and stabilized. These molecules are to be antigenic in addition to their functions of maintain-ing cell membrane structural stability, material transport and exchange of cells and signal transmission between cells. The antigenic molecules on the erythrocyte surface are called erythrocyte blood group antigens. The blood group antigens and their corresponding blood group antibodies in vivo are important indicators for clinical blood transfusion and organ transplantation, and also form the basis for research on blood group related diseases. Three hundred and sixty-eight erythrocyte blood group antigens have been confirmed so far, which are classified into 39 blood group systems, 5 blood group collections and 2 blood group series. Based on the diversity of blood group antigens and their composition of glycolipids, glycoproteins and other molecules, this study mainly reviews the classification, molecular structure, antibody response and gene regulation of blood group antigens, and explains the main reasons for the diversity of blood group antigens.

Prevalence and specificity of some rare red cell pan-reactive alloantibodies against high frequency red cell antigens among hospitalized Saudi patients

Samy Attallah, Tarek Hakeem, Ebrahim Hamdy, Zyiad AlHarby, Faisal Althubiani, Ershad Dade, Abdulla AlHarbi

2020, 4(2): 123-128. doi: 10.46701/BG.2020022020126

Abstract(75) HTML Full Text (19) PDF(404KB)(5)

Abstract:
Some patients' sera react with all available donors' red cells and a compatible donor is difficult or impossible to be found. These may either be due to a complex mixture of antibodies or the presence of alloantibodies against high-frequency antigens (HFAs). The aim of this study is to identify the prevalence and characteristics of antibodies to HFAs in Saudi Arabian patients. A total of 23 out of 172 000 patients who received blood transfusions had rare alloantibodies to HFAs at an incidence of 0.013%. Twenty-three patients suspected with pan-reactive alloantibodies against HFAs had their red cells tested using antisera to HFAs, while their plasma was tested against a selected panel of red blood cells with rare phenotypes. Anti-Ge2 antibody was found in the highest number of patients (56.5%), whereas anti-U, anti JK3, anti H, anti-RH 29, anti-hr^s, anti-Kn^a, anti-Ch, anti-Rg, anti-Yt^a, and anti-Cr^a antibodies were found in the remaining patients (43.5%). This study suggests that although antibodies such as anti-Ge2, anti-Kn^a, anti-Ch, anti-Rg, anti-Yt^a, and anti-Cr^a are not clinically significant, they cause a delay in the provision of compatible blood. Whereas, anti-U, anti JK3, anti H, anti-RH29 and anti-hr^s are clinically significant antibodies. An understanding of antibody characteristics to HFAs and the widespread use of the extended red cell phenotype and antibody identification panel will both be helpful for the diagnosis of these HFAs.

Clinical features and hematological findings of COVID-19 patients with blood transfusion

Yanhong Zhang, Shangen Zheng, Qiang Zhou, Yu Zhang, Yao Zheng, Shun Wang, Lei Liu

2020, 4(2): 129-135. doi: 10.46701/BG.2020022020125

Abstract(37) HTML Full Text (11) PDF(950KB)(1)

Abstract:
This paper aims to illustrate the clinical characteristics, hematological findings, and blood transfusion information of Coronavirus disease 2019 (COVID-19) patients. Twenty-three COVID-19 patients were treated and trans-fused with blood products in Wuhan First Hospital from February 12 to March 20, 2020. The patients were divided into a survivor group and a non-survivor group, respectively, according to whether the patient had been discharged or died. The results demonstrated at the time of initial blood transfusion, that the non-survivor group possessed a lower platelet (PLT) than that of the survivor group (P < 0.001), and PLT were below the normal range in 6 (85.7%) non-survivor group and in 2 (12.5%) survivor group (P < 0.01). Over half of these patients had abnormalities in fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT), and international nor-malized ratio (INR), but no significant difference was found between the non-survivor group and survivor group. The non-survivor group had a dramatically higher D-Dimers and disseminated intravascular coagulation (DIC) scores than those of the survivor group (P < 0.01). Six (85.7%) non-survivors but none of the survivors had a DIC score greater than 6 (P < 0.001). Fifteen (93.8%) survivors and 2 (28.6%) non-survivors were transfused with RBC (P < 0.01). The non-survivors (5/7) possessed a higher proportion for using AP than the survivors (2/16). The study suggests that COVID-19 patients who undergo blood transfusion usually possess coagulation dysfunction, and DIC may be closely related to deteriorating clinical outcomes.

Serological and genetic analysis of ABO ambiguous blood group samples

Ying Li, Jinming Xu, Yongliang Zhu, Ting Xiong, Ling Zhao, Yun Yao, Xiaoyu Zhou

2020, 4(2): 136-141. doi: 10.46701/BG.2020022020112

Abstract(86) HTML Full Text (25) PDF(1605KB)(7)

Abstract:
The accuracy of regular serum methods to detect ABO blood groups can be negatively affected by some factors, such as irregular antibodies, autoantibodies or effects of diseases leading to false or weak agglutination. This study aimed to accurately identify ambiguous ABO blood groups by serological and gene detection methods. The samples were collected in the First Affiliated Hospital of Nanjing Medical University from December 2018 to December 2019. ABO genotyping was performed by polymerase chain reaction-sequence specific primer (PCR-SSP) method in 20 samples, and ABO exons 6 and 7 or FUT1 and FUT2 genes were sequenced in 5 samples. The genes detected in the 21 specimens included 4 cases of A/B, 2 cases of A205/O01, 3 cases of A/O01, 3 cases of A/O02, 1 case of O01/O01, 1 case of O01/O02, 1 case of B/O01, 1 case of B/O02, 1 case of Bel/O01, 1 case of Cisab01/O01, 1 case of rare B/O04, 1 case of Bombay-like Bmh, 1 case of new gene showing c.261del G of exon 6, c.579 T > C of exon 7 and B new/O01. This study suggests that ABO blood group genotyping technology combined with serological typing can be used for accurately typing ambiguous blood groups.

High LIMP2 expression serves as a predictor for improved clinical outcomes in gastric cancer patients

Pei Chen, Shiwen Wang, Bo Chen, Bing Lu, Xiaojing Zhang, Xiaohui Jiang, Yao Wang

2020, 4(2): 142-150. doi: 10.46701/BG.2020022020119

Abstract(48) HTML Full Text (17) PDF(3275KB)(0)

Abstract:
Lysosomal integral membrane protein-2 (LIMP2) is an important component of innate immunity. However, its role in the anti-tumor response remains unknown. Here, we found that the level of LIMP2 mRNA was frequently upregulated in gastric cancer (GC) tissues according to the TCGA, which was confirmed by immunohistochemistry in 329 cases. LIMP2 expression was significantly associated with Lauren classification (P=0.042), depth of invasion (P=0.016), lymph node metastasis (P=0.039) and TNM stage (P=0.027). LIMP2 expression (P < 0.001), differentiation (P < 0.001), TNM stage (P < 0.001) and preoperative CEA (P=0.018) can be used as independent prognostic factors. GC patients with higher levels of LIMP2 mRNA experienced improved clinical outcomes. Mechanically, the TGF-β signaling pathway, the ERBB signaling pathway, and Toll-like receptor signaling were enriched in proteins with higher LIMP2. Moreover, LIMP2 expression was positively related with M1 tumor-associated macrophages (TAMs) in TCGA data, which was verified by capturing LIMP2 and CD86 co-expression in GC samples. The study suggests that LIMP2 expression in GC would predict improved outcomes with M1 TAMs infiltration.

RhCE-D (2)-CE hybrid allele causing puzzle in serology and sequencing: a case report

Jing Wang, Changyan Li, Lian Duan, Wenjun Que, Yan Xing, nTan Bi, Tingxi Zhan, Zebo Yu

2020, 4(2): 151-155. doi: 10.46701/BG.2020022020113

Abstract(112) HTML Full Text (29) PDF(1515KB)(5)

Abstract:
The Rh locus, one of the important blood group systems in transfusion medicine, is controlled by three highly homologous genes: RHAG, RHD and RHCE. RHD and RHCE genes both contain 10 exons with opposite orientation, with genetic homology of higher than 92%. Based on this arrangement and configuration, a hybridization variant easily occurs, which causes variant or weak antigen expression. A 46-year-old woman of group A was admitted to hospital with bloody stool. Her RhD phenotype was confusing (agglutination < 1+) as detected by gel card. The unexpected antibody was identified to be anti-D. Only exon 2 of RHD was detected by sequence-speci?c primer polymerase chain reaction (SSP-PCR) with hybrid heterozygosis of c.150T > C, c.178A > C, c.201G > A, and c.307T > C by sequencing. The genotype of RHCE was confirmed to be Ccee by SSP-PCR and the serologic phenotype was Ccee too. However, the sequencing of RhCE was confirmed to be ccee with c.178CC, c.203AA, c.307CC on exon 2. Further analysis found that the difference between them depended on the replacement of exon 2 from RhD. The genotype of this patient was found to be RhCE-D(2)-CE/RhCE, leading to a confusing RhD phenotype.

B para-Bombay phenotype in China caused by homozygous mutation for site 328 G > A of FUT1 gene: a case report

Zelan Gu, Chun Li, Hua Lu

2020, 4(2): 156-158. doi: 10.46701/BG.2020022020116

Abstract(47) HTML Full Text (13) PDF(354KB)(5)

Abstract:
The aim of this paper is to accurately identify a case of B para-Bombay and to analyze the genetic mutation. ABO and Lewis blood groups were identified by standard serological methods, and trace antigens on RBCs were detected by adsorption-elution test, while blood group substances in the saliva were detected by agglutination inhibition test. The ABO gene exons 6-7, FUT1 gene exon 4 and FUT2 gene exon 2 were directly sequenced. Serological results showed that there were B antigens on RBCs without H antigens, anti-A and anti-HI antibodies in serum, and B and H blood group substances in the saliva. The Lewis phenotype was Le (a-b+). According to gene sequencing analysis, ABO, FUT1 and FUT2 genotypes were B101/O02, h^328G/Ah3^28G/A and Se^357C/TSe^357C/T, respectively. This rare phenotype can be mislabeled as "O" if any of the detailed investigations are not performed. Therefore, in order to ensure the safety of blood transfusion, genetic and serological tests are necessary for the correct identification of difficult blood groups.

Rare B(A)02/O01 was found in Sichuan again: a case report

Jie Wang, Lin Gui, Weixin Zhou, Jianbo Yang, Yuanshuai Huang

2020, 4(2): 159-161.

Abstract(54) HTML Full Text (16) PDF(4527KB)(2)

Abstract:
B(A) is a rare ABO blood subgroup. Here we reported a B(A)02/O01 case. One 25-year-old female patient showed inconsistent forward and reverse blood grouping results based on micro-column gel agglutination assay. PCR-SSP and PCR-SBT based genotyping indicated that the patient was B(A)02/O01 heterozygous.

2020 Vol. 4, No. 2