What is the C antigen in the Rh blood group system?

The C Antigen in the Rh Blood Group System

The C antigen is one of the five major antigens in the Rh blood group system (D, C, c, E, e) and is found in approximately 95.5% of the population. 1, 2

Characteristics of the C Antigen

• The C antigen is part of the Rh blood group system, which is one of the most polymorphic and immunogenic blood group systems in humans 3
• It is encoded by the RHCE gene, which can express either C or c antigens along with either E or e antigens 1, 3
• The C antigen is found in approximately 95.5% of the population, making it one of the more common Rh antigens after the e antigen (96.8%) 2
• The C antigen can be determined by either serologic testing or molecular genotyping 1

Clinical Significance

Alloimmunization Risk

• Antibodies against the C antigen can develop in C-negative individuals who are exposed to C-positive blood through transfusion or pregnancy 4
• Anti-C antibodies can cause:
  • Acute hemolytic transfusion reactions
  • Delayed hemolytic transfusion reactions
  • Hemolytic disease of the fetus and newborn (HDNF) 4

Transfusion Considerations

• For patients with sickle cell disease (SCD), the American Society of Hematology (ASH) strongly recommends prophylactic red cell antigen matching for Rh (C, E or C/c, E/e) and K antigens over only ABO/RhD matching 1
• This recommendation is based on moderate certainty evidence showing that extended matching significantly reduces alloimmunization rates 1
• Studies have demonstrated that Rh- and K-matched red cells have an alloimmunization incidence rate of 0.9 per 100 transfused units compared to 3.1 for ABO/RhD-matched red cells only 1

Special Considerations

Variant C Antigens

• Some individuals may express partial or variant C antigens due to genetic variations in the RHCE gene 1, 5
• Patients identified by genotype with hybrid RHDDIIIa-CE (4-7)-D or RHCECeRN alleles encode partial C antigens 1
• These patients should receive C-negative red cells to prevent allo-anti-C development, even though they technically express a form of the C antigen 1

Testing Methods

• Blood typing for the C antigen should be performed in clinical laboratory settings using standardized methods such as hemagglutination or gel column techniques 6
• Extended phenotyping, including C antigen testing, is recommended for patients who may require multiple transfusions 6
• Molecular genotyping provides improved accuracy for C antigen typing compared to serologic methods, especially in recently transfused patients or those with interfering antibodies 1

Rare Phenotypes

• The Rhnull phenotype is characterized by the absence of all Rh antigens, including C, and is associated with chronic hemolytic anemia 7
• DIVa(C)- is a rare complex phenotype involving weak C expression and several low-prevalence Rh antigens 5

Clinical Applications

• Extended antigen typing, including C antigen, is particularly important for:
  • Patients with sickle cell disease
  • Chronically transfused patients
  • Patients who have already developed alloantibodies
  • Pregnant women with a history of hemolytic disease of the fetus and newborn 1, 6

Understanding the C antigen and its role in the Rh blood group system is essential for safe transfusion practices and prevention of alloimmunization, particularly in high-risk patient populations.