人源化的ABO抗体 BioVector NTCC质粒载体菌种细胞基因保藏中心

人源化的ABO抗体

The ABO blood group The discovery of the ABO blood group, over 100 years ago, caused great excitement. Until then, all blood had been assumed to be the same, and the often tragic consequences of blood transfusions were not understood. As our understanding of the ABO group grew, not only did the world of blood transfusion become a great deal safer, but scientists could now study one of the first human characteristics proven to be inherited. A person's ABO blood type was used by lawyers in paternity suits, by police in forensic science, and by anthropologists in the study of different populations. The ABO blood group antigens remain of prime importance in transfusion medicine—they are the most immunogenic of all the blood group antigens. The most common cause of death from a blood transfusion is a clerical error in which an incompatible type of ABO blood is transfused. The ABO blood group antigens also appear to have been important throughout our evolution because the frequencies of different ABO blood types vary among different populations, suggesting that a particular blood type conferred a selection advantage (e.g., resistance against an infectious disease.) However, despite their obvious clinical importance, the physiological functions of ABO blood group antigens remain a mystery. People with the common blood type O express neither the A nor B antigen, and they are perfectly healthy. Numerous associations have been made between particular ABO phenotypes and an increased susceptibility to disease. For example, the ABO phenotype has been linked with stomach ulcers (more common in group O individuals) and gastric cancer (more common in group A individuals). Another observation is that individuals with blood type O tend to have lower levels of the von Willebrand Factor (vWF), which is a protein involved in blood clotting. Go to: At a glance Antigens of the ABO blood group Number of antigens 4: A, B, AB, and A1 Antigen specificity Carbohydrate The sequence of oligosaccharides determines whether the antigen is A, B, or A1. Antigen-carrying molecules Glycoproteins and glycolipids of unknown function The ABO blood group antigens are attached to oligosaccharide chains that project above the RBC surface. These chains are attached to proteins and lipids that lie in the RBC membrane. Molecular basis The ABO gene indirectly encodes the ABO blood group antigens. The ABO locus has three main allelic forms: A, B, and O. The A and B alleles each encode a glycosyltransferase that catalyzes the final step in the synthesis of the A and B antigen, respectively. The A/B polymorphism arises from several SNPs in the ABO gene, which result in A and B transferases that differ by four amino acids. The O allele encodes an inactive glycosyltransferase that leaves the ABO antigen precursor (the H antigen) unmodified. Frequency of ABO blood group antigens A: 43% Caucasians, 27% Blacks, 28% Asians B: 9% Caucasians, 20% Blacks, 27% Asians A1: 34% Caucasians, 19% Blacks, 27% Asians Note: Does not include AB blood groups (1). Frequency of ABO phenotypes Blood group O is the most common phenotype in most populations. Caucasians: group O, 44%; A1, 33%; A2, 10%; B, 9%; A1B, 3%; A2B, 1% Blacks: group O, 49%; A1, 19%; A2, 8%; B, 20%; A1B, 3%; A2B, 1% Asians: group O, 43%; A1, 27%; A2, rare; B, 25%; A1B, 5%; A2B, rare Note: Blood group A is divided into two main phenotypes, A1 and A2 (1). Antibodies produced against ABO blood group antigens Antibody type IgG and IgM Naturally occurring. Anti-A is found in the serum of people with blood groups O and B. Anti-B is found in the serum of people with blood groups O and A. Antibody reactivity Capable of hemolysis Anti-A and anti-B bind to RBCs and activate the complement cascade, which lyses the RBCs while they are still in the circulation (intravascular hemolysis). Transfusion reaction Yes — typically causes an acute hemolytic transfusion reaction Most deaths caused by blood transfusion are the result of transfusing ABO-incompatible blood. Hemolytic disease of the newborn No or mild disease HDN may occur if a group O mother has more than one pregnancy with a child with blood group A, B, or AB. Most cases are mild and do not require treatment. Go to: Background information History At the beginning of the 20th century an Austrian scientist, Karl Landsteiner, noted that the RBCs of some individuals were agglutinated by the serum from other individuals. He made a note of the patterns of agglutination and showed that blood could be divided into groups. This marked the discovery of the first blood group system, ABO, and earned Landsteiner a Nobel Prize. Landsteiner explained that the reactions between the RBCs and serum were related to the presence of markers (antigens) on the RBCs and antibodies in the serum. Agglutination occurred when the RBC antigens were bound by the antibodies in the serum. He called the antigens A and B, and depending upon which antigen the RBC expressed, blood either belonged to blood group A or blood group B. A third blood group contained RBCs that reacted as if they lacked the properties of A and B, and this group was later called "O" after the German word "Ohne", which means "without". The following year the fourth blood group, AB, was added to the ABO blood group system. These RBCs expressed both A and B antigens. In 1910, scientists proved that the RBCs antigens were inherited, and that the A and B antigens were inherited codominantly over O. There was initially some confusion over how a person's blood type was determined, but the puzzle was solved in 1924 by Bernstein's "three allele model". The ABO blood group antigens are encoded by one genetic locus, the ABO locus, which has three alternative (allelic) forms—A, B, and O. A child receives one of the three alleles from each parent, giving rise to six possible genotypes and four possible blood types (phenotypes). Image ABO_T3.jpg Nomenclature Number of ABO blood group antigens: 4 ISBT symbol: ABO ISBT number: 001 Gene symbol: ABO Gene name: ABO blood group (A transferase, α1,3-N-acetylgalactosaminyltransferase; B transferase, α1,3-galactosyltransferase) Go to: Basic biochemistry ABO phenotypes The four basic ABO phenotypes are O, A, B, and AB. After it was found that blood group A RBCs reacted differently to a particular antibody (later called anti-A1), the blood group was divided into two phenotypes, A1 and A2. RBCs with the A1 phenotype react with anti-A1 and make up about 80% of blood type A. RBCs with the A2 phenotype do not react with anti-A1 and they make up about 20% of blood type A. A1 red cells express about 5 times more A antigen than A2 red cells, but both types of red cell react with anti-A, and as far as transfusion purposes are concerned, the A1 and A2 blood groups are interchangeable. There are many other subgroups of blood group A in which RBCs tend to weakly express the A antigen, whereas weak variants of the blood group B phenotype are rare (2). The immune system forms antibodies against whichever ABO blood group antigens are not found on the individual's RBCs. Thus, a group A individual will have anti-B antibodies and a group B individual will have anti-A antibodies. Blood group O is common, and individuals with this blood type will have both anti-A and anti-B in their serum. Blood group AB is the least common, and these individuals will have neither anti-A nor anti-B in their serum. Image ABO_T4.jpg ABO antibodies in the serum are formed naturally. Their production is stimulated when the immune system encounters the "missing" ABO blood group antigens in foods or in micro-organisms. This happens at an early age because sugars that are identical to, or very similar to, the ABO blood group antigens are found throughout nature. The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that produces the A antigen (N-acetylgalactosamine is its immunodominant sugar), and the B allele encodes a glycosyltransferase that creates the B antigen (D-galactose is its immunodominant sugar). See the structures of the A, B, and O antigens in Stryer's Biochemistry The O allele encodes an enzyme with no function, and therefore neither A or B antigen is produced, leaving the underlying precursor (the H antigen) unchanged. These antigens are incorporated into one of four types of oligosaccharide chain, type 2 being the most common in the antigen-carrying molecules in RBC membranes. Some of the other enzymes involved in the earlier stages of ABO antigen synthesis are also involved in producing antigens of the Hh blood group and the Lewis blood group.

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