Children's National Hospital Washington, DC, District of Columbia, United States
Background/Case Studies: A patient was seen for Possible Sickle Crisis, and a Type and Screen was ordered for transfusion. The OPOS patient also presented with Anti-D. Sample was sent to American Red Cross for examination prior to transfusion to ensure proper care and treatment. The patient had a long history of transfusions for Sickle Cell Disease. Patient types 3 - 4+ Rh Positive (C-E-c+e+) presented as possible allo-Anti-D.
Study
Design/Methods: American Red Cross extracted DNA from whole blood using Qiagen DNA Extraction Kit following the manufacturer’s instructions, using PCR amplification.
Results/Findings: Patient was identified to have both a variant RHD gene as well as a homozygous variant RHCE gene. The RHD variant RHD*IIIa-CE(4-7)-D (RHD*DAU3) allele which encodes an altered C antigen (instead of RhD) was identified. This represents a hybrid allele, where a portion of the RHD gene has been replaced by sequences from the RHCE gene. This hybrid allele is linked to the RHCE03 allele and is commonly found in individuals with sickle cell disease (SCD).
This patient was also identified as homozygous for a variant RHCE*ce allele known as RHCE*ce48C (common in African descent). This allele carries a genetic change at a single nucleotide position (SNP) 48, where a cytosine (C) is replaced by a guanine (G). This SNP change then results in a change in the encoded protein, which causes p.Trp16Cys. the specific amino acid changes at the 16th position in the RHCE protein, from Tryptophan (Trp), to Cysteine (Cys). As a result, the RhCE protein encoded by this allele will express c and e antigens, but it might have altered reactivity with certain anti-e antibodies.
Conclusions: I
Individuals carrying this type of RHD variant may have altered expression of the D antigen and may be at risk of forming allo-anti-D antibodies when exposed to the D antigen. In addition, RHCE*ce48C in sickle cell disease where Trp16Cys is observed and is linked to a weakened or altered expression of the e antigen will complicate blood typing and transfusion compatibility. Based on this analysis, the patient is at risk for developing the following allo-antibodies: allo-Anti-D, -C, and f(ce). While this can lead to altered reactivity with some anti-e antibodies, it's generally not associated with clinically significant allo-anti-e production. Accurate identification and understanding of both such RHD and RHCE variants through molecular testing is crucial for safe blood transfusion practices and preventing alloimmunizations; especially in patients with conditions like sickle cell disease who require frequent transfusions.
