Study Notes on Blood Groups and Lewis System

Other Blood Group Systems

Introduction to Blood Groups

  • Blood Group:
    • An inherited character (antigen) on the red cell surface, identified by specific alloantibodies.
    • Detected antigens are polymorphic.
    • Composed of inherited carbohydrate or protein structures on the red blood cell (RBC) membrane surface.

Importance of Blood Group Antigens

  • Detection and identification of blood group antigens and antibodies is vital for:
    • Safe blood transfusion practices.
    • Management of pregnancies at risk for hemolytic disease of the fetus and newborn (HDF/N).

Immune Responses Associated with Blood Groups

  • Antigens from other blood group systems may cause immune responses during transfusion or pregnancy.
  • Some antibodies produced are clinically significant in transfusion medicine.
    • Over 300 unique red cell antigens and 36 blood group systems recognized by the International Society of Blood Transfusion (ISBT).
  • Understanding blood group systems is key to addressing complex antibody issues efficiently.

Red Blood Cell Membrane Components

Diagram Overview

  • Structure includes:
    • Single-pass proteins
    • Multi-pass proteins
    • Glycosylphosphatidylinositol (GPI)-linked proteins
  • Features several identified blood group antigens like Kell, Duffy, Rh, and MNS.
    • Diagram illustrates the lipid bilayer of the RBC membrane with various antigen-carrying components.

Classification of Blood Group Antigens

  • Two main categories of blood group antigens:
    • Carbohydrate-based:
    • Found on glycolipids or glycoproteins.
    • Examples: Lewis, P, Ii, ABO, and H blood groups.
    • Protein-based:
    • Composed of amino acids associated with protein structures on RBC membrane.
    • Examples: MNS, Duffy, Kell, Kidd, Rh, and Lutheran.
  • Blood group antigens themselves are not functionally significant; their roles derive from the molecules they reside upon.

Major Blood Group Systems

  • There are nine major blood group systems:
    • ABO
    • Rhesus (Rh)
    • Kell (K)
    • Lewis (Le)
    • Duffy (Fy)
    • Kidd (Jk)
    • MNSs
    • I
    • P

Clinical Significance of Blood Group System Antibodies

  • Clinical Significance:
    • Antibodies that decrease RBC survival, causing transfusion reactions and HDFN.
  • Not Clinically Significant:
    • Antibodies not causing RBC destruction.
  • Cold-reacting antibodies:
    • Agglutination best observed at room temperature or cooler.
  • Warm-reacting antibodies:
    • Agglutination best observed at 37°C.
  • Dosage:
    • Antibodies that demonstrate dosage show stronger reactions with homozygously expressed RBC antigens.

Lewis Blood Group Details

Overview

  • Discovered post-World War II (1946-1948); comprises six carbohydrate-based antigens carried on circulating glycolipids.
  • Two main antigens defined serologically: Lea (LE1) and Leb (LE2).
  • Four additional antigens resulting from interactions with Lea, Leb, and ABO:
    • Leab (LE3)
    • LebH (LE4)
    • ALeb (LE5)
    • BLeb (LE6)

Antigen Synthesis

  • Synthesized by endodermal cells and incorporated into the RBC membrane from Lewis-active glycosphingolipids (GSL) in plasma, not of erythroid origin.
  • Present also on platelets, lymphocytes, and endothelium, with soluble forms in plasma, saliva, breast milk, and urine.

Lewis Blood Group Phenotypes

Phenotypes

  • Four possible Lewis phenotypes, with three commonly observed in adults:
    • Le(a+b−)
    • Le(a−b+)
    • Le(a−b−)
  • Le(a+b+) is rare and seen mainly in neonates and certain Asian populations.
  • Phenotypes vary by race and geography.
  • Sensitive to changes in RBC turnover; conditions like pregnancy and chronic renal failure can decrease Lewis strength.

Synthesis and Inheritance of Lewis Antigens

Genetic Basis

  • Genes on chromosome 19p13.3 involved:
    • H (FUT1)
    • Se (FUT2, secretor)
    • Le (FUT3)

Antigen Formation

  • Lea produced from type 1 chain precursor (LeC) through a pathway requiring FUT3 only.
  • Leb requires both FUT2 and FUT3; cannot be synthesized directly from Lea due to steric hindrance.
  • Modification of Leb by ABO leads to ALe b (LE5) and BLeb (LE6).
  • In individuals of ABO type A1, ALeb is the most prevalent Lewis-active GSL in plasma.

Phenotype Inheritance Patterns

  • Le(a+b−) phenotype indicates one functional FUT3 and homozygosity for FUT2-null alleles (se/se).
  • Le(a−b+) indicates at least one functional FUT3 and FUT2, leading to both Lea and Leb expression.
  • Absence of Lea is deceptive; both Lea and Leb are synthesized, with competitive expression leading to Leb predominance.
  • Le(a−b−) phenotype lacks functional FUT3 and may or may not secrete Lewis-active substances depending on FUT2 inheritance.

Lewis Blood Group Phenotypes and Incidence

Phenotype Frequencies

PhenotypeFrequency (%)Reactions with Anti-LeaReactions with Anti-Leb
Le(a+b−)22 (Whites), 23 (Blacks)+0
Le(a−b+)72 (Whites), 55 (Blacks)0+
Le(a−b−)6 (Whites), 22 (Blacks)++
Le(a+b+)RareRare-

Biological Roles of Lewis Antigens

  • Lea antigen serves as a receptor for E-selectin, an important adhesive molecule in cancer biology.
  • Le(a−b−) phenotype linked to a doubled risk of atherosclerotic disease; associated with lower triglyceride levels.
  • Lewis antigens interact with Helicobacter pylori, linking them to gastritis and peptic ulcer disease.

Lewis Antibodies

  • Generally low-titer, IgM saline agglutinins, largely clinically insignificant.
  • Rare exceptions exist with limited association with HDFN and hemolytic transfusion reactions.
  • Typically found in sera of Le(a−b−) individuals; some literature links them to increased kidney transplant rejection risk.
  • Lewis antibodies may show ABO reactivity, with stronger reactions noted in group O and A RBCs.