BB-ABO BLOOD GROUPS

• ABO GROUP

  • Discovered by Dr. Karl Landsteiner via mixing cells and serum
  • The most important blood group in transfusion practice
  • Individuals have antibodies in their serum against the antigens absent from their RBCs. When incompatible, it may result in destruction of donor RBCs or “Transfusion reactions”
• ABO Inheritance

  • Follows simple Mendelian genetics
  • Group O gene is considered an “Amorph”, and is an autosomal recessive trait with the inheritance of two O genes that are nonfunctional
  • The A, B, or O gene is located on Chromosome 9
  • ABO is inherited via codominant in expression. The ABO genes are inherited one from each parent.
• FORMATION OF ABH ANTIGENS

  • Formation depends on three genes from three separate loci (ABO, Hh, Se) - these genes code for the production of glycosyltransferases that adds sugar to the precursor substance.
  • Develops at second month of fetal life and will stay forever.
  • The precursor substance is the PARAGLOBOSIDE or GLYCAN
  • = it can be Type 1 precursor with a beta 1-3 linkage between a galactose and N-acetylglucosamine
  • = Type 2 = terminal galactose linked to the N-acetylglucosamine in a beta 1-4 linkage.
  • RBC ABO antigens are constructed from Type 2 Precursors.
• Formation of ABH Antigens

  
  

  A and B genes depends on the H gene action (H gene is at chromosome 19)

  1. HH
  2. Hh
  3. hh = rare, doesn't have H antigen = Bombay phenotype

  H gene is inherited independently from ABO genes.
• Formation of ABH Antigens

  The ABO gene is located on chromosome 9 and consist of seven exons and spans about 18 to 20 kb

  • Last two exons encode for the catalytic domain of the ABO glycosyltransferases (most in 7)
• Formation of ABH Antigens

  H Antigen Formation

  • The H gene (FUT1) codes for 1,2 Fucosyl Transferase that adds the sugar “Fucose” to the terminal galactose of type 2 precursor, thus forming the H antigen.
  • The Se gene (FUT2) codes for 1,2 Fucosyl Transferase that adds the sugar Fucose to terminal galactose of a type 1 precursor, thus forming the H antigen in secretions
• Formation of ABH Antigens

  A Antigen Formation

  • The A gene codes for 1,3 N-acetylgalactosaminyl transferase which joins the sugar “N-acetyl-D-galactosamine” to the terminal galactose of an H antigen

  B antigen Formation

  • The B gene codes for 1,3 galactosyl transferase which adds Galactose to the terminal galactose of an H antigen
• O Transferases

  • Group O phenotype results from any mutation in an A or B transferase gene that causes loss of glycosyltransferase activity and nonfunctional enzyme
  • Most common (Group O01) results from a single nucleotide deletion early in the gene near the N - Terminus, the deletion causes a frameshift and a truncated product with no enzyme activity.
  • Other problem is from Group O02 with a nucleotide deletion and nine point mutations
• ABH Antigens

  ABO Antigens

  • Carbohydrate structures composed of glycoproteins and glycolipids
  • RBC membrane proteins carry over 2 x 10^6 A or B or H antigens mostly located on the major integral membrane protein, Band 3.
  • Found in Platelets
  • Can also be found on other tissues like endothelial and epithelial cells of the lungs and gut, epithelial cells of the urinary and reproductive tracts
• ABH Antigens

  ABO incidence

  • Group B is found usually in African Americans and Asians (11% in Whites, 20% in Blacks)
  • Group A and Group O are the most common, found in Asians (40-45% in whites, 50% in blacks)
  • Group AB is the rarest
• ABH Antigens

  H antigen

  • Basic antigenic material of ABO
  • Found in greatest concentrations on the RBCs of group O individuals
  • Detected by an anti-H antiserum (Ulex europeus)
  • O > A2 > B > A2B > A1 > A1B
• Secretor Genes = ABO Histo-blood group Antigens

  • Controls the presence of A and B on secretions
  • ABH antigens are found on secretions of people with the secretor phenotype (Se)
  • Se gene or FUT2 gene
  • An individual who inherits the Se allele in either homozygous or heterozygous manner is classified as a SECRETOR
  • Determination = ABH test on saliva
• Secretor Genes Genotypes

  • SeSe = secretes A, B, H antigen in saliva, sweat, urine, milk, tears
  • Sese = secretes A, B, H antigen in saliva, sweat, urine, milk, tears
  • sese = non-secretors (se allele is an amorph)
• Bombay Phenotype (Oh)

  • Inheritance of "hh" gene, no H substance = RBCS does not react with anti-H lectin (Ulex europaeus)
  • First reported by Dr. Bhende in 1952 in Bombay, India
  • The person can inherit A or B genes but has no H substance, no ABH antigens.
  • Caused by a mutation in FUT1 gene, produces a SILENCED GENE.
• Bombay Phenotype (Oh)

  • Fails to react with Anti-A, B or H and sometimes mistyped as O.
  • Bombay serum contains Anti-A, Anti-B, and Anti-AB.
  • Bombay blood group is rare and can only be found in 4 out of 1 million people.
  • Only Bombay phenotype cells should be transfused to Bombay phenotype people.

  Anti-H (produced by Bombay phenotypes) = an IgM that reacts at 37C.
• Para-Bombay Phenotypes

  • Phenotypes where RBCs completely lack H antigens or have only small amounts of H antigen present
  • A and/or B enzymes can be detected but not the H enzyme
  • = The “Ah” and “Bh” are used to describe these people
  • = In Bh individuals, anti-A and anti-B may be detected
  • RBCs express weak forms of A and B antigens which are only detected in elution techniques.
  • Anti-H produced is weaker but still reactive at 37C