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Partial expression of RHc on the RHD polypeptide
B H Faas1, E A Beuling, P C Ligthart
1Department of Experimental Immunohematology, Central Laboratory of the Netherlands Blood Transfusion Service.
Insights
The Rh blood group system
Area of Science:
- Immunogenetics
- Molecular biology
- Blood group serology
Background:
- The Rh blood group system is crucial in transfusion medicine.
- The c antigen is highly immunogenic, second only to D.
- Understanding Rh antigen expression is vital for preventing transfusion reactions.
Purpose of the Study:
- To investigate a novel partial c phenotype.
- To identify the genetic basis of this partial c phenotype.
- To determine the role of specific mutations in Rh antigen expression.
Main Methods:
- Serological testing of red blood cells (RBCs) with anti-c reagents.
- Genomic DNA and complementary DNA (cDNA) sequence analysis.
- Transduction studies using K562 erythroleukemic cells.
Main Results:
- Identified a new partial c phenotype (D(c)).
- Discovered two point mutations (307T>C and 329T>C) in the RHD allele, with 307T>C leading to S103P.
- Demonstrated that the mutated RHD allele likely encodes the c antigen.
- Confirmed expression of c in K562 cells transduced with the mutated RHD cDNA.
Conclusions:
- The amino acid at position 103 (P103) is critical for c antigen expression.
- The c antigen can be expressed on the RhD polypeptide in vivo.
- This finding advances the understanding of Rh blood group genetics and immunogenicity.
Background:
In the human Rh blood group system, c is, after D, the most immunogenic antigen.
Study Design And Methods:
The background of a new partial c phenotype (D(c)), identified on the RBCs of two unrelated white persons, was studied. This was done by analyzing the reactivity of the RBCs from the donors with anti-c reagents, by performing sequence analysis, and by carrying out transduction studies.
Results:
Serologic results suggested the existence of a new partial c phenotype. Genomic DNA and cDNA analysis revealed a normal RHCe allele, a normal RHD allele, and an RHD allele that carried two point mutations: 307T>C and 329T>C (the latter known to be associated with the DVII, Tar-positive phenotype). No normal RHc allele was found. Thus, it was most likely that c is encoded by the mutated RHD allele (phenotype DD(c)CCee). Indeed, subsequent transduction of K562 erythroleukemic cells with an RHD cDNA carrying the 307T>C point mutation (leading to S103P) resulted in the expression of c.
Conclusion:
In the human Rh system, P103 is involved in the expression of c. Moreover, c can be expressed in vivo on the D polypeptide.