Model Answer
0 min readIntroduction
The human blood group system, particularly the ABO system, is a cornerstone of transfusion medicine and genetic studies. The expression of A and B antigens on red blood cells is dependent on a precursor substance, the H antigen. The H antigen is not directly involved in the ABO blood group determination but is essential for its manifestation. A rare genetic condition, known as the Bombay phenotype (also called Oh phenotype), arises from the absence of the H antigen, leading to unique immunological consequences and diagnostic challenges. This answer will detail the nature of the H antigen and its critical role in the emergence of the Bombay phenotype.
Understanding the H Antigen
The H antigen is a precursor molecule to the A and B antigens. It is a tetrasaccharide structure (fucose-galactose-glucosamine-N-acetylgalactosamine) present on the surface of red blood cells. Its synthesis is governed by the FUT1 gene (also known as the H gene), which encodes the enzyme α1,2-fucosyltransferase. This enzyme catalyzes the addition of fucose to the H antigen precursor, completing the H antigen structure.
The Genetic Basis of the Bombay Phenotype
The Bombay phenotype is characterized by the absence of the H antigen on red blood cells. This occurs due to a homozygous recessive mutation (hh) in the FUT1 gene. Individuals with this genotype lack functional α1,2-fucosyltransferase, preventing the synthesis of the H antigen.
How Absence of H Antigen Impacts ABO Expression
Since the A and B antigens are synthesized by adding N-acetylgalactosamine (for A) or galactose (for B) to the H antigen precursor, the absence of H antigen effectively blocks the expression of both A and B antigens. Consequently, individuals with the Bombay phenotype will phenotypically appear as blood group O, regardless of the ABO alleles they possess (e.g., they can be genetically AA, BB, AB, or AO, BO, but will serologically test as O).
Immunological Implications
Individuals with the Bombay phenotype do not produce anti-H antibodies under normal circumstances. However, if exposed to red blood cells expressing the H antigen (through transfusion or pregnancy), they will rapidly develop strong anti-H antibodies. This makes finding compatible blood for transfusion extremely difficult, as almost all blood types express the H antigen. They can only receive blood from other individuals with the Bombay phenotype.
Illustrative Example
Consider an individual with the genotype AAhh. Genetically, they possess the A allele, which would normally lead to the expression of the A antigen. However, because they are homozygous for the recessive h allele, they lack the functional α1,2-fucosyltransferase and cannot synthesize the H antigen. Consequently, they cannot add N-acetylgalactosamine to the H antigen precursor, and therefore do not express the A antigen. Their blood type will be phenotypically O.
Distinguishing Bombay Phenotype from Blood Group O
Standard ABO blood typing will identify individuals with the Bombay phenotype as blood group O. However, further testing, such as testing for anti-H antibodies and performing absorption-elution studies, is necessary to confirm the diagnosis. Absorption-elution studies involve incubating the patient’s serum with H antigen-positive red blood cells, which absorb the anti-H antibodies. Elution of the antibodies from the red cells confirms their specificity for the H antigen.
| Feature | Blood Group O | Bombay Phenotype (Oh) |
|---|---|---|
| Genotype (ABO) | OO | AA, BB, AB, AO, BO (can be any) |
| H Antigen | Present | Absent |
| Anti-H Antibodies | Absent | Present (after exposure to H antigen) |
| ABO Typing | O | O |
| Further Testing | Not required | Required (anti-H antibody testing, absorption-elution) |
Conclusion
The H antigen serves as a crucial precursor for the expression of A and B antigens in the ABO blood group system. The Bombay phenotype, resulting from a homozygous recessive mutation in the <em>FUT1</em> gene, highlights the importance of the H antigen. Understanding this rare genetic condition is vital for accurate blood typing, safe transfusion practices, and genetic counseling. Continued research into the genetic factors influencing blood group antigen expression remains essential for improving patient care and advancing our understanding of human genetic diversity.
Answer Length
This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.