Minor Blood Groups

• The Lewis blood group system:

  • Inheritance pattern: Autosomal dominant
  • Genes producing the alleles: Lewis (Le, FUT3) gene on chromosome 19 at position 19p13.3, secretor (Se, FUT2) gene at 19q13.3
  • Antigens: Lewis a (Le^a) and Lewis b (Le^b)
  • Characteristics of Lewis a:
  • Formed by adding α(1,4)-fucose residue to precursor chains
  • Predominantly found in secretions like saliva, gastric mucosa, and amniotic fluid
  • Synthesized by the FUT3 gene
  • Characteristics of Lewis b:
  • Formed by adding β(1,3)-galactose and α(1,4)-fucose residues to precursor chains
  • Predominant Lewis antigen on red blood cells
  • Synthesized by both FUT2 and FUT3 genes
  • Prevalence: Varies among populations, more common in European descent
  • Antibodies: Lewis antibodies are naturally occurring, primarily IgM, and do not cross the placenta
• P blood group system:

  • Inheritance pattern: Autosomal recessive
  • Genes producing the alleles: P1PK gene (A4GALT) on chromosome 22 at 22q13.2, Globoside gene (B3GALNT1) on chromosome 3 at 3q25
  • Antigens: P1, P, Pk
  • Characteristics of P antigens: Synthesized by glycosyltransferases, found on various cells
  • Antigen formation: P1 antigen poorly expressed at birth, may take years to fully express
  • Antibodies: Anti-P antibodies are usually IgM, can cause hemolytic transfusion reactions or hemolytic disease of the newborn
• Lewis antibodies:

  • Naturally occurring, primarily IgM
  • Made by Le(a-b-) individuals
  • Anti-Le(a) and anti-Le(b) may occur together
  • Frequently found in pregnant women with Le(a-b-) phenotype
  • Anti-Le(a) most commonly encountered, often detected in room temperature tests
• P1 antigen:

  • Poorly expressed at birth, may take years to fully express
  • Antigen strength varies among individuals
  • Expression can vary with race, deteriorates rapidly on storage
• Anti-P antibodies:

  • Usually IgM, can cause hemolytic transfusion reactions or hemolytic disease of the newborn
  • Formed following exposure to P antigen through transfusion or pregnancy
  • IgM antibodies, large pentameric molecules
• Clinical significance of Lewis system antigens:

  • Uncommonly clinically significant
  • Unique in immunohematology as they are not produced by red blood cells themselves
• Clinical significance of P blood group antigens:

  • The only red cell antigens not produced by the red blood cells themselves
  • Can cause hemolytic transfusion reactions or hemolytic disease of the newborn if antibodies are present
• Importance of understanding Lewis antigens and antibodies in immunohematology practice:

  • Essential for recognizing unique red cell antigens not produced by red blood cells
  • Understanding genetics, characteristics, and clinical significance is crucial
• Importance of understanding P blood group antigens and antibodies in immunohematology practice:

  • Crucial for identifying antigens that can cause hemolytic reactions
  • Knowledge of inheritance patterns and antibody formation is essential
• Genes producing P blood group alleles:

  • P1PK gene (A4GALT) on chromosome 22 at 22q13.2
  • Globoside gene (B3GALNT1) on chromosome 3 at 3q25
• Characteristics of P blood group antigens:

  • Synthesized by glycosyltransferases
  • Found on various cells like RBCs, lymphocytes, granulocytes, monocytes, platelets, epithelial cells, and fibroblasts
• Formation of Lewis antigens:

  • Linked to specific glycosyltransferase enzymes encoded by FUT3 and FUT2 genes on chromosome 19
  • Lewis a (Le^a) formed by adding α(1,4)-fucose residue, while Lewis b (Le^b) results from additional glycosylation steps
• Formation of P1 antigen:

  • Poorly expressed at birth, may take years to fully express
  • Expression varies among individuals and races
  • Deteriorates rapidly on storage
• Formation of anti-P antibodies:

  • Typically formed following exposure to P antigen through transfusion or pregnancy
  • IgM antibodies, can cause hemolytic reactions
• Anti-P antibodies are usually of the IgM class, which are large pentameric molecules effective at agglutinating red blood cells and activating complement, leading to hemolysis
• Anti-P antibodies exhibit cold agglutination, agglutinating red blood cells at temperatures below normal body temperature, typically around 4°C
• The Donath-Landsteiner antibody, a specific type of anti-P antibody, is a cold agglutinin that causes hemolysis of red blood cells when exposed to cold temperatures, followed by warming
• The Donath-Landsteiner antibody is typically associated with paroxysmal cold hemoglobinuria (PCH), a rare autoimmune hemolytic anemia
• Clinical significance of anti-I and anti-i antibodies:

  • Anti-I associated with cold agglutinin disease and M. pneumoniae
  • Anti-i associated with infectious mononucleosis
  • Increased i antigen on RBCs associated with various conditions like acute leukemia, hypoplastic anemia, megaloblastic anemia, etc.
• Inheritance pattern of I and i antigens:

  • Autosomal-recessive
  • The IGnT (GCNT2) gene on chromosome 6 at position 6p24 produces the alleles
• Characteristics of I and i antigens:

  • I and i are carbohydrate structures formed by glycosyl transferases
  • At birth, infant RBCs are rich in i; I increases with age until adult proportions are reached
• Formation of anti-I antibodies:

  • Anti-I is a common autoantibody found in most sera
  • Autoanti-I is benign and usually a weak, naturally occurring, saline-reactive IgM agglutinin
• Clinical significance of anti-I antibodies:

  • Acute CAD associated with Mycoplasma pneumoniae
  • Increased i antigen expression in various conditions like megaloblastic anemia, leukemia, and chronic hemolytic states
• Inheritance pattern of MNS antigens:

  • Codominance
  • Genes GYPA and GYPB on chromosome 4 at position 4q31.21 produce the alleles
• Characteristics of anti-M antibodies:

  • Naturally occurring saline agglutinins reacting below 37°C
  • Anti-M more common in children and in patients with bacterial infections
• Characteristics of anti-N antibodies:

  • Anti-N can demonstrate dosage, reacting better with specific RBC types
  • Anti-N less common than anti-M, with potent anti-N in individuals lacking N and GPB activity
• Characteristics of anti-S and anti-s antibodies:

  • IgG antibodies reactive at 37°C and the antiglobulin phase of testing
  • More likely to be clinically significant than anti-M and anti-N antibodies
• Clinical significance of MNS antigens:

  • MNS antigens can serve as receptors for complement, bacteria, and viruses
  • 10GPAM may serve as the receptor for certain pyelonephritogenic strains of E. coli
• Inheritance pattern of Kell antigens:

  • Autosomal recessive
  • The KEL gene on chromosome 7 at position 7q33 determines the Kell blood group system
• Characteristics of Kell antigens:

  • Presence or absence of the Kell antigen on red blood cells determines Kell positivity or negativity
  • Antibodies against the Kell antigen can cause severe transfusion reactions and hemolytic disease of the newborn
• Formation of Kell antigens:

  • Begins with the KEL gene on chromosome 7, which codes for the Kell glycoprotein
  • Minor and uncommon Kell antigens can arise from genetic variations in the KEL gene, leading to different amino acid sequences or structural changes in the Kell glycoprotein
  • Variations may lead to the expression of additional antigens like Kpb, Js^b, Kpc, Kpa, K11, K12, among others
• Antibodies against Kell antigens:

  • Develop in individuals without these antigens when they encounter them through transfusions, pregnancies, or previous pregnancies
  • Predominantly of the IgG type
  • Can induce severe reactions during transfusions or cause hemolytic disease of the newborn (HDN) if they pass through the placenta during pregnancy
• McLeod phenotype:

  • The Kell blood group system is clinically significant due to its potential to cause severe transfusion reactions and hemolytic disease of the newborn (HDN)
• Clinical significance of Kell antigens:

  • Highly immunogenic
  • Kell antibodies can cause transfusion reactions when incompatible blood is transfused
  • Reactions can range from mild to severe, including hemolytic transfusion reactions
• Formation of Duffy antigens:

  • Duffy antigens FYA and FYB can be identified on fetal RBCs as early as 6 weeks gestational age
  • Well developed at birth
  • Prevalence varies among different races: relatively frequent in Caucasians and Asians, less common in Blacks
• Antibodies against Duffy antigens:

  • Rare but can occur in individuals who lack the corresponding antigen on their red blood cells
  • Typically IgG and can cause hemolytic transfusion reactions or hemolytic disease of the newborn if the mother has the antibodies and the fetus inherits the corresponding antigen from the father
• Clinical significance of Duffy antigens:

  • Important in blood transfusions, organ transplantation, and hemolytic disease of the newborn
  • Understanding an individual's Duffy phenotype is crucial in preventing adverse reactions during transfusions or transplantation and managing pregnancies where maternal antibodies against Duffy antigens may pose a risk to the fetus
• Inheritance pattern of Kidd antigens:

  • Jka and Jkb antigens are products of two alleles inherited in a co-dominant fashion
  • Jk(a-b-) phenotype is generally inherited as a recessive trait
• Characteristics of Kidd antigens:

  • Jka and Jkb antigens are commonly found on RBCs of most individuals and well developed on neonatal RBCs
  • Jka is slightly more common in African Americans, while Jkb is slightly more common in whites and Asians
  • Jk3 antigen is present on any RBC positive for Jka or Jkb
• Antigen formation in Kidd blood group system:

  • Major antigens Jka and Jkb result from allelic variation in the SLC14A1 gene
  • Jk3 antigen is present on any RBC expressing Jka or Jkb
  • Minor antigens Jk4, Jk5, and Jk6 arise from further allelic variation within the SLC14A1 gene