Antigen Prevalence
The prevalence of a blood group antigen refers to how frequently it occurs within a specific population. It’s essentially asking: “What percentage of people have this particular antigen on their red blood cells?” Understanding antigen prevalence is absolutely critical in transfusion medicine because it directly impacts several key areas: the likelihood of encountering specific antibodies, the ease or difficulty of finding compatible blood, and strategies for managing patient transfusions, especially those requiring long-term support
Antigen Prevalence: A Numbers Game
Prevalence is usually expressed as a percentage. We can broadly categorize antigens based on their prevalence:
-
High-Prevalence Antigens (“Public” Antigens)
- Definition: Found on the red blood cells of the vast majority of people, typically >99% of the population
- Examples: k (Cellano), Kpb, Jsb, Lub, U, Vel, Emm, Ge3, Yta, I, P
-
Transfusion Implications
- Antibodies are Rare: Because almost everyone has the antigen, very few people are capable of making an antibody against it (they see it as “self”)
- Finding Compatible Blood is Extremely Difficult: If a patient does develop an antibody to a high-prevalence antigen (because they are one of the rare individuals lacking it), sourcing antigen-negative blood is a major challenge. This often requires screening thousands of donors, accessing national/international Rare Donor Programs, or testing family members
-
Low-Prevalence Antigens (“Private” Antigens)
- Definition: Found on the red blood cells of only a small percentage of the population, often <1% up to maybe 10%
- Examples: K (Kell), Kpa, Jsa, Lua, Wra, Dia (in non-Asian/Native American populations), Cw, V
-
Transfusion Implications
- Antibodies are Relatively Uncommon: Although the antigens can be immunogenic (like K), exposure through transfusion or pregnancy is less frequent simply because the antigen isn’t common in the donor/paternal population
- Finding Compatible Blood is Usually Easy: If a patient develops an antibody to a low-prevalence antigen, the vast majority of random donors will lack the antigen and thus be compatible. The main challenge here is often detecting and identifying the antibody in the first place, as it might be missed by routine screening cells and only appear as an incompatible crossmatch
-
Intermediate or Variable Prevalence Antigens
- Definition: Antigens with frequencies that fall between the extremes, often varying significantly between populations
- Examples: ABO antigens (A, B), Rh antigens (D, C, c, E, e), Kidd antigens (Jka, Jkb), Duffy antigens (Fya, Fyb), MNS antigens (M, N, S, s)
-
Transfusion Implications
- Antibodies are Common: Antibodies to antigens in these systems are frequently encountered in patient testing (either naturally occurring like anti-A/B, or immune-stimulated like anti-D, -K, -E, -c, -Fya, -Jka)
- Finding Compatible Blood Varies: The ease of finding compatible blood depends on the specific antigen and the patient/donor populations. For example, finding D-negative blood is straightforward in Caucasian populations (~15% are D-neg) but much harder in Asian populations (<1% D-neg). Finding blood negative for common combinations (like R1R1 needing R2R2 blood) requires considering the prevalence of specific Rh phenotypes
Population Variation: A Critical Factor
It is absolutely essential to remember that antigen prevalence figures are population-specific. An antigen common in one ethnic group may be rare in another
- RhD: D-negative phenotype is ~15% in Caucasians, ~5-8% in individuals of African descent, <1% in Asians
- Duffy: Fy(a-b-) phenotype is common (~70%) in individuals of African descent (conferring resistance to Plasmodium vivax malaria) but extremely rare in Caucasians and Asians
- Diego: Dia is rare in Caucasians/Africans but common (up to 30%+) in East Asians and Native Americans
- Kell: Jsa is common (~20%) in individuals of African descent but rare (<0.1%) in Caucasians
- MNS: U-negative phenotype (lacking Glycophorin B) is found almost exclusively in individuals of African descent (~1%)
Why Prevalence Matters in the Blood Bank
- Predicting Antibody Likelihood: Knowing prevalence helps estimate the chance a patient might have a particular antibody. If a patient is negative for a high-prevalence antigen, the chance of encountering that antigen (and thus forming an antibody) is high if transfused randomly
-
Compatibility Testing Strategy
- Antibody to High-Prevalence Ag: Triggers a search for rare blood
- Antibody to Low-Prevalence Ag: Focus shifts to confirming ID; finding units is usually easy
- Antibody to Intermediate-Prevalence Ag: Requires selecting appropriately phenotyped units based on standard inventory
- Donor Inventory Management: Blood centers need to understand the prevalence of various antigens in their donor population to ensure an adequate supply of commonly needed and rarer phenotypes
- Managing Chronically Transfused Patients: Patients with conditions like sickle cell disease often develop multiple antibodies. Knowing antigen prevalence within their ethnic group is vital for providing extended phenotype-matched blood to prevent further alloimmunization
- Interpreting Antibody Screens/Panels: The frequency of reactions on a panel can give clues. An antibody reacting with almost all cells suggests an antibody to a high-prevalence antigen. An antibody reacting with only one cell might indicate an antibody to a low-prevalence antigen
Key Terms
- Prevalence: The proportion or percentage of individuals in a defined population who express a specific antigen
- High-Prevalence Antigen: An antigen present on the red cells of >99% of the population
- Low-Prevalence Antigen: An antigen present on the red cells of <1-10% of the population
- Population Variation: Significant differences in antigen frequencies observed between different ethnic or geographic groups
- Rare Donor Program: A registry or system for identifying and accessing blood donors with rare phenotypes (e.g., lacking high-prevalence antigens)
- Antithetical Antigen: One of a pair of antigens encoded by alleles at the same gene locus. Often, if one is high prevalence, its partner is low prevalence (e.g., k vs. K)