Blood group Rh(CE) polypeptide (c antigen) (RHCE)

The Rh c antigen is a highly immunogenic protein polymorphism located on the Blood group Rh(CE) polypeptide (RHCE), a multi-pass transmembrane protein essential for red blood cell (RBC) membrane integrity (UniProt P18577). Encoded by the RHCE gene, the 'c' antigen (also known as Rh4) is defined by a specific amino acid substitution (Pro103) on the second extracellular loop of the protein (PubMed: 3135863). RHCE functions as part of the Rh-RhAG complex, which is involved in ammonium and carbon dioxide transport and provides a critical attachment site for the ankyrin-1 complex to the RBC cytoskeleton (PubMed: 35835865). Clinically, the 'c' antigen is the most significant Rh antigen after the D antigen, as anti-c antibodies are a leading cause of severe hemolytic disease of the fetus and newborn (HDFN) and delayed hemolytic transfusion reactions (StatPearls: NBK2267). While no specific prophylactic immune globulin exists for the 'c' antigen, management of sensitized pregnancies involves monitoring antibody titers and potentially using treatments like intravenous immunoglobulin or emerging FcRn inhibitors like nipocalimab to reduce fetal risk (PubMed: 32110829). In transfusion medicine, matching for the 'c' antigen is particularly critical for patients with sickle cell disease to prevent alloimmunization and subsequent hemolytic complications (PubMed: 29296782). The protein's role in maintaining the RBC's structural stability is evidenced by the Rh-null phenotype, where the absence of Rh proteins leads to stomatocytosis and chronic hemolytic anemia (PubMed: 1135522).

Other names

Rh polypeptide 1Rh30ARhIXBRhesus C/E antigensCD240CERh4SLC42A4Rhesus blood group CcEe proteinRh-c antigen

Pathogenic maternal IgG antibodies bind to the 'c' antigen on fetal red blood cells, leading to their destruction by fetal splenic macrophages (extravascular hemolysis). Therapeutic strategies include blocking the neonatal Fc receptor (FcRn) with drugs like nipocalimab to prevent the placental transfer of these antibodies or using IVIG to saturate Fc receptors and inhibit hemolysis.