Preface

Every individual is born with a set of antigenic substances inherited from their parents. These special molecules are mainly present on the membrane surface of red blood cells. These structures can be sugars, proteins, or a special set of enzymes that can make an individual prone to or protected against various infections and other diseases.

Besides the ABO blood group, there are more than thirty-seven other systems with more than 300 blood group antigens present in the human blood. These blood group structures not only perform a critical role in the function of cells but can also be used by viruses to gain access to cells.

This book includes nine chapters on different blood group antigens and their activities behind the scenes.

Chapter 1, "Are ABO Gene Alleles Responsible for Cardiovascular Diseases and Venous Thromboembolism, and Do They Play a Role in COVID?" by Kaneez Fatima Shad et al. discusses the association between ABO blood groups and cardiovascular diseases (CVD). The authors discuss how individuals with non-O blood group type are at increased risk of coronary heart disease, myocardial infarction, cerebral ischemic stroke, peripheral arterial disease, and venous thromboembolism (VTE) including deep vein thrombosis and pulmonary thromboembolism. The most likely mechanism in all cases is thought to be the increase in von Willebrand Factor (vWF) and factor VIII levels seen in patients with a non-O blood group. The increased levels in vWF and factor VIII among individuals with a non-O blood group who have contracted SARS-CoV-2 infection may result in an additive thrombophilic effect to that caused by the virus.

Chapter 2, "Human Blood" by Francisca Varpit and Vela Galama discusses the red cell component of human blood, specifically red cell membranes and the antigens found on them. This chapter briefly covers the genetic inheritance of common antigens, the important structural makeup of red cells, antibody response to these antigens, and their functions in health (physiological) and disease (pathophysiological). Some of these blood group antigens maintain the structural integrity of red blood cells and play a role in the cationic exchange between intracellular and extracellular molecules, without which red cells become disfigured resulting in a reduction in their survival and increased risk of hematological diseases. These antigens can also serve as transporters, adhesion molecules, and receptor proteins relaying chemical messages from cell to cell. However, these mechanisms have been exploited by infectious agents to gain entry into the human body causing disease.

Chapter 3, "ABO Blood Group and Thromboembolic Diseases" by Yetti Hernaningsih discusses the division between type O and non-O blood groups due to the presence of antigens on the cell surface and antibodies in plasma and their relationship in the onset of thromboembolic diseases in the non-O blood group due to higher levels of VWF and FVIII. The author further discusses how arterial thromboembolic events are often associated with cardiovascular diseases, and deep vein thrombosis (DVT) and pulmonary embolism (PE) with venous thromboembolism (VTE).

Chapter 4, "Duffy Antigens and Malaria: The African Experience" by Chima Akunwata describes the Duffy antigen/chemokine receptor (DARC), which is located on the surface of red blood cells. It is a receptor for pro-inflammatory chemokines and for the invasion of Plasmodium vivax into the red blood cells. A point mutation in the promoter region of the Duffy gene disrupts the binding of a transcription factor leading to a lack of expression of the antigen on the erythrocytes. This Duffy negative phenotype is found predominantly in the African population. This mutation is advantageous as individuals with the Fy(a-b-) phenotype are less susceptible to P. vivax malaria. It is believed that the absence of Duffy antigen in most Africans contributed to the resistance to P. vivax and by extension reduced the burden of malaria in these endemic areas.

Chapter 5, "Blood Groups: More than Inheritance of Antigenic Substances - Susceptibility to Some Diseases" by Williams Bitty Azachi and Kuschak Mathias Dakop links diseases such as infections, coagulopathy, coronary, malignancy, and malaria with ABO blood groups. The authors' findings reveal that the O blood group has a greater frequency of severe infections such as Escherichia coli and cholera, whereas blood group A is associated with the incidence of smallpox and some bacterial infections. These observations are principally based on the presence or absence of "H-like" and "A and B-like" antigen markers. Antigens A, B, and H are connected to N-glycans of vWF and reduce the half-life of this protein to 10 hours for group O and 25 hours for non-O groups. This explains the reason for increased levels of vWF in non-O individuals. This phenomenon raises the possibility of coagulopathy in non-O groups. Similarly, some tumors have A or A-like antigens, which explains the tendency of group A individuals to develop tumors. The A-like antigens of tumor cells are seen as foreign in B and O blood types with resultant immune responses.

Chapter 6, "RH Groups" by Amr J. Halawani describes a hemolytic disease of the newborn, now known as hemolytic disease of the fetus and newborn (HDFN), due to the presence of antigens in the RH blood group system. To date, fifty-six antigens have been recognized within the RH blood group system. The five main antigens are D, C, c, E, and e, and the antibodies to these antigens are implicated in hemolytic transfusion reactions (HTR) and HDFN.

Chapter 7, "Neutrophil-Specific Antigens: Immunobiology, Genetics, and Roles in Clinical Disorders" by Parviz Lalezari and Behnaz Bayat is about neutrophil-specific antigens (i.e., NA and NB), which are responsible for inducing febrile and potentially fatal lung injury and causing graft rejection in bone marrow transplantation. In clinical studies, it is also demonstrated that NB expression is highly elevated in polycythemia vera, and in some carcinomas, NB is expressed on the tumor cells. Neutrophil-specific antigens are examples of structures that beyond antigenicity have important biological activities and clinical implications.

Chapter 8, "The ABO Blood Group System and *Plasmodium falciparum* (*Pf*) Infection in Three Ethnic Groups Living in the Stable and Seasonal Malaria Transmission Areas of Burkina Faso (BF)" by Edith Christiane Bougouma et al. discusses the importance of blood group and its role in the onset of Plasmodium falciparum (Pf) infection. It also discusses the role of two specific genetic polymorphisms (rs8176719 and rs8176746) on such infections. The authors demonstrate that the Fulani ethnic group is not only less susceptible to Pf malaria infection but also has lower parasite densities when infected. The authors suggest that the origin, distribution, and relative proportion of ABO blood groups in humans may have been directly influenced by selective genetic pressure from P. falciparum infection.

Chapter 9, "ABO Blood Groups and Glioma" by Ana Azanjac Arsic is a modified version of the author's previous publication "ABO blood groups and risk of glioma: A case-control study from Serbia" published in 2017. The aim of this case-control study was to investigate the possible association between the incidence of glioma and certain blood groups. Univariate binary logistic regression analysis revealed that individuals with group AB were at a 3.5-fold increased risk of developing glioma compared to individuals with other ABO blood groups. Mechanisms that explain the relationship between blood groups ABO and cancer risk are unclear. Several hypotheses have been proposed, including a modulatory role of blood group ABO antigens and regulation of the level of circulating proinflammatory and adhesion molecules, which are important for tumorigenesis by the blood group ABO system. One of the possible explanations for the role of the blood group ABO in the tumorigenesis process is the recent discovery of vWF, which is an important modulator of angiogenesis and apoptosis. The results of the study suggest that the blood group AB may be one of the hereditary factors that have an influence on the occurrence of glioma.

I would like to thank Author Service Manager Maja Bozicevic at IntechOpen for her hard work, constant support, and help.

This book is meant for a range of readers with different levels of interest in these incredible antigens, which are not only defining our blood groups but are also responsible for protecting us from the infection caused by bacteria and viruses.

> **Kaneez Fatima Shad** School of Life Sciences, University of Technology Sydney, Sydney, Australia

## **Chapter 1**
