Blood group systems biosynthesis (Homo sapiens)
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Description
The association between blood type and disease has been studied since the beginning of the 20th Century (Anstee 2010, Ewald & Sumner 2016). Landsteiner's discovery of blood groups in 1900 was based on agglutination patterns of red blood cells when blood types from different donors were mixed (Landsteiner 1931, Owen 2000, Tan & Graham 2013). His work is the basis of routine compatibility testing and transfusion practices today. The immune system of patients receiving blood transfusions will attack any donor red blood cells that contain antigens that differ from their self-antigens. Therefore, matching blood types is essential for safe blood transfusions. Landsteiner's classification of the ABO blood groups confirmed that antigens were inherited characteristics. In the 1940s, it was established that the specificity of blood group antigens was determined by their unique oligosaccharide structures. Since then, exponential advances in technology have resulted in the identification of over 300 blood group antigens, classified into more than 35 blood group systems by the International Society of Blood Transfusion (ISBT) (Storry et al. 2016).
Blood group antigens comprise either a protein portion or oligosaccharide sequence attached on a glycolipid or glycoprotein. The addition of one or more specific sugar molecules to this oligosaccharide sequence at specific positions by a variety of glycosyltransferases results in the formation of mature blood group antigens. The genes that code for glycosytransferases can contain genetic changes that produce antigenic differences, resulting in new antigens or loss of expression. Blood group antigens are found on red blood cells (RBCs), platelets, leukocytes, and plasma proteins and also exist in soluble form in bodily secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions and urine. Blood groups are implicated in many diseases such as those related to malignancy (Rummel & Ellsworth 2016), the cardiovascular system (Liumbruno & Franchini 2013), metabolism (Meo et al. 2016, Ewald & Sumner 2016) and infection (Rios & Bianco 2000, McCullough 2014). The most important and best-studied blood groups are the ABO, Lewis and Rhesus systems. The biosynthesis of the antigens in these systems is described in this section. View original pathway at Reactome.
Blood group antigens comprise either a protein portion or oligosaccharide sequence attached on a glycolipid or glycoprotein. The addition of one or more specific sugar molecules to this oligosaccharide sequence at specific positions by a variety of glycosyltransferases results in the formation of mature blood group antigens. The genes that code for glycosytransferases can contain genetic changes that produce antigenic differences, resulting in new antigens or loss of expression. Blood group antigens are found on red blood cells (RBCs), platelets, leukocytes, and plasma proteins and also exist in soluble form in bodily secretions such as breast milk, seminal fluid, saliva, sweat, gastric secretions and urine. Blood groups are implicated in many diseases such as those related to malignancy (Rummel & Ellsworth 2016), the cardiovascular system (Liumbruno & Franchini 2013), metabolism (Meo et al. 2016, Ewald & Sumner 2016) and infection (Rios & Bianco 2000, McCullough 2014). The most important and best-studied blood groups are the ABO, Lewis and Rhesus systems. The biosynthesis of the antigens in these systems is described in this section. View original pathway at Reactome.
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Increased sialylation has been associated with malignant transformation and metastasis. ST3GAL6 is highly expressed in patients with multiple myeloma (MM). Knockdown of ST3GAL6 has been shown to prolong survival in mice (Glavey et al. 2014).