Which genotype is most likely to produce antibodies in the Lewis (Le) system, which involves the production of Le^a and Le^b antigens on red blood cells (RBCs)?

Lewis Blood Group System Antibody Production

Individuals with the genotype LeLe Sese (option A) would be the most likely to produce antibodies in the Lewis system.

Understanding the Lewis Blood Group System

The Lewis blood group system is determined by the interaction of two key genes:

• The Lewis gene (FUT3) which encodes an α(1,3/1,4)-fucosyltransferase
• The Secretor gene (FUT2) which encodes an α(1,2)-fucosyltransferase

These genes work together to create the Lewis antigens that can be found on red blood cells and in body secretions.

Genetic Basis for Lewis Antigen Production

The Lewis phenotype is determined by:

• Le gene: Responsible for producing the Lewis enzyme that creates Lewis antigens
• Se gene: Determines whether Lewis antigens are secreted into body fluids

Lewis Phenotypes and Antibody Production

There are three main Lewis phenotypes:

• Le(a+b-): Individuals with Le gene but lacking functional Se gene (Lele/LeLe with sese)
• Le(a-b+): Individuals with both functional Le and Se genes (Lele/LeLe with Sese/SeSe)
• Le(a-b-): Individuals lacking functional Le gene (lele with any Se genotype)

Analysis of the Genotypes

Let's analyze each genotype option:

1. LeLe Sese (Option A):

   • Has functional Lewis gene (LeLe)
   • Lacks functional Secretor gene (sese)
   • Phenotype: Le(a+b-)
   • Most likely to produce anti-Le^b antibodies as they cannot produce Le^b antigen

2. lele sese (Option B):

   • Lacks functional Lewis gene (lele)
   • Lacks functional Secretor gene (sese)
   • Phenotype: Le(a-b-)
   • Cannot produce Lewis antigens, but also typically doesn't produce Lewis antibodies

3. Lele Sese (Option C):

   • Has functional Lewis gene (Lele)
   • Has functional Secretor gene (Sese)
   • Phenotype: Le(a-b+)
   • Produces both Le^a and Le^b antigens (though Le^a is converted to Le^b)
   • Unlikely to produce Lewis antibodies

4. LeLe sese (Option D):

   • Has functional Lewis gene (LeLe)
   • Lacks functional Secretor gene (sese)
   • Phenotype: Le(a+b-)
   • Same as Option A

Mechanism of Antibody Production

Individuals with the Le(a+b-) phenotype (LeLe sese or Lele sese) are most likely to produce anti-Le^b antibodies because:

• They have a functional Lewis gene allowing them to produce Le^a antigen
• They lack a functional Secretor gene, preventing conversion of Le^a to Le^b
• Since they cannot produce Le^b antigen, they can form antibodies against it when exposed

Clinical Significance

The production of Lewis antibodies has implications for:

• Blood transfusion compatibility
• Tissue typing for organ transplantation
• Diagnostic testing in certain diseases

Conclusion

Based on the genetic principles of the Lewis blood group system, individuals with the LeLe Sese genotype (Option A) would be most likely to produce antibodies in the Lewis system, specifically anti-Le^b antibodies, as they have a functional Lewis gene but lack the Secretor gene necessary to produce Le^b antigen.