anti-Blood Group Lewis A Monoclonal antibody, clone U175

In 1946, Mourant first discovered a natural antibody in the serum of a patient named Lewis, which reacted with about 22% of the red blood cells of the British people and was called anti-Lea. In 1948, Andresen discovered anti-Leb antibodies. The Lewis antigen corresponding to the above antibody is the Lewis substance in the plasma adsorbed on the red blood cells. The real Lewis substance exists in the secretion fluid or plasma. Lea and Leb are not synthesized by red blood cells. They are regarded as blood type antigens because they were first discovered on red blood cells. Because these two antigens are not determined by a pair of alleles, naming them Lea and Leb are sometimes confusing. In 1951, Grubb proposed the concept of Lewis blood type, believing that it is better to divide Lewis blood type according to whether Lewis blood type substances are present in saliva rather than dividing Lewis blood type according to red blood cell antigens. This view was confirmed by many subsequent experiments and led to the formation of our concept of Lewis blood type today. In 1955, based on the results of a family survey, Ceppellini proposed that the expression of Lea antigen in saliva is controlled by a pair of alleles Le and le at the Lewis locus, with the former being dominant over the latter. The Lewis gene is functionally independent of the secretory gene.

Figure 1. Terminal oligosaccharide structures determining the Lewis antigens and the ABO blood group antigens. (Sources: Magalh?es A, et al. 2010)

The Lewis blood group system contains 6 antigens. The main antigens are Lea and Leb. These antigens are not synthesized by red blood cells, but are soluble antigens present in saliva and plasma. Red blood cells acquire the Lewis phenotype by adsorbing Lewis substances from plasma onto red blood cells. The antigenic properties are glycosyl antigenic determinants on glycoproteins and glycolipids on the cell membrane. ABH and Lewis antigens are called tissue-blood group antigens, and their gene products come from the same precursor substance: H (FUT1) antigen is the basis for ABO gene expression; ABH's secretory Se (FUT2) plays an important role in determining the Lewis phenotype, and Lewis (FUT3) antigen is a blood group antigen adsorbed from plasma onto the red blood cell membrane. The precursors of the Lewis blood group gene FUT3 and the secretory FUT2 gene products are both type I sugar chains, and there is a substrate competition relationship between the two. When the FUT2 gene is expressed normally (SE), the individual cannot produce Lea antigen, only Leb antigen; when the FUT2 gene mutates (se) and cannot be expressed normally, Lea antigen is produced without Leb antigen. Therefore, individuals with the Le(a+b-) phenotype are generally non-secreting, and individuals with the Le(a-b+) phenotype are generally secreting. In addition to Lea and Leb, Lewis blood group system antigens also include Leab, Lebh, ALeb, and BLeb. Antigens related to the Lewis system include Lec (210001) and Led (210002), which are "precursor" antigens of Lewis antigens and currently still belong to the "blood group set". Lex and Ley are type II sugar chain isomers, and sialy-Lex is a ligand of the cell adhesion protein (selectin) family. The Leab antigen was discovered in 1949 and mistakenly identified as Lex in 1950. It was confirmed by ISBT in 1988 as an independent Leab antigen. Leab is a high-frequency antigen. About 90% of Le (a+b-) and Le (a-b+) phenotype red blood cells have Leab. The Lebh antigen was discovered in 1984 and confirmed by ISBT in 1988. Lebh is a polymorphic antigen. Lebh is weakly expressed or not expressed on O-type and A2-type Le (b+) phenotype red blood cells. Lebh is weakly expressed in pregnant women with Le(a+b+) phenotype or when some diseases occur. Lebh antigen is a type I sugar chain antigen. ALeb antigen was discovered in 1967 and confirmed by ISBT in 1998. ALeb is also a polymorphic antigen. ALeb only exists on A1 type Le(b+) phenotype red blood cells, and does not exist on O type and B type Le(b+) phenotype red blood cells. ALeb is a secretory antigen and a type I sugar chain antigen. BLeb antigen was discovered in 1998 and confirmed by ISBT. BLeb is a polymorphic antigen. BLeb is only expressed on B type Le(b+) phenotype red blood cells, and does not express on O type and A type Le(b+) red blood cells. BLeb is also a secretory antigen and a type I sugar chain antigen.

Anti-Lea can only appear in the plasma of individuals with Le (a-b-) secretory type. It is rare to appear in O-type individuals. It is usually a natural antibody, mainly IgM. Most strong anti-Lea sera contain IgG components, which can be detected by radioimmunoassay or enzyme-linked immunosorbent assay. Anti-human globulin method cannot detect it. Literature has reported that anti-Lea may activate complement and cause severe acute hemolytic transfusion reactions. Therefore, patients with anti-Lea antibodies in the body need to transfuse antigen-negative red blood cells. Anti-Leb is even rarer, and most of them will not cause severe hemolytic reactions. The concentration of lipoproteins in pregnant women's plasma increases, and more Lewis antigenic determinants are adsorbed to plasma lipoproteins, while those adsorbed to the surface of red blood cells are correspondingly reduced. A transient Le (a-b-) change can lead to the production of antibodies. It was reported that a pregnant woman with Le (a-b+) blood type had strong anti-Leb antibodies in her plasma at 7 months of pregnancy, and the anti-Leb antibodies disappeared 3 months after delivery. Some women with Le (a-b+) often become Le (a-b-) during pregnancy. This change can be detected as early as 24 weeks of pregnancy, and they return to Le (a-b+) 6 weeks after giving birth.

Anti-Lea Antibodies
Anti-Lewis a Antibodies
Anti-Blood Group Antibodies Lewis A
Anti-Lewis System A Antibodies