Two MER2-negative individuals with the same novel CD151 mutation and evidence for clinical significance of anti-MER2.
BACKGROUND
MER2 (RAPH1), the only antigen of the RAPH blood group system, is located on the tetraspanin CD151. Only four examples of alloanti-MER2 are known. We report here two new examples of alloanti-MER2, in women of Pakistani and Turkish origin, one of whom showed signs of a hemolytic transfusion reaction (HTR) after transfusion of 3 units of red cells (RBCs).


METHODS
Standard serologic methods were used. A monocyte monolayer assay (MMA) was used to assess the potential clinical significance of one of the antibodies. All exons and flanking intronic sequences of CD151 were amplified and sequenced. A homology model for CD151 second extracellular loop (EC2) was constructed based on the crystal structure of CD81.


RESULTS
RBCs of both patients did not react with alloanti-MER2, and neither of their antibodies reacted with MER2-negative RBCs. The MMA results suggested that the antibody that appeared to have caused an HTR had the potential to be clinically significant. Both patients were homozygous for a 511C>T mutation in CD151 encoding an Arg171Cys change. This change did not result in any significant structural rearrangement in the protein model.


CONCLUSIONS
Two MER2-negative patients with anti-MER2 are homozygous for the same novel mutation encoding an amino acid substitution in the EC2 of CD151. One of the antibodies may have been responsible for an HTR, and crossmatch-compatible RBCs should be recommended for transfusion to patients with anti-MER2.
Bristol Institute for Transfusion Sciences and International Blood Group Reference Laboratory, Bristol, UK. vanja.crew@nbs.nhs.uk
Vanja
V
Karamatic Crew
Joyce
J
Poole
Shannon
S
Long
Nicole
N
Warke
Connie
C
Colavecchia
Nicholas
N
Burton
Marilyn
M
Moulds
Gloria
G
Schlanser
Laura
L
Wilson
Ghislain
G
Noumsi
Joann M
JM
Moulds
John J
JJ
Moulds
Geoff
G
Daniels
D000369:Aged, 80 and over; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D001789:Blood Group Antigens / Q000235:genetics* / Q000276:immunology; D005260:Female; D006801:Humans; D007518:Isoantibodies / Q000276:immunology; D008958:Models, Molecular; D009154:Mutation; D011110:Polymorphism, Genetic; D017433:Protein Structure, Secondary; D060185:Tetraspanin 24; D065227:Transfusion Reaction
D015703:Antigens, CD; D001789:Blood Group Antigens; C554715:CD151 protein, human; D007518:Isoantibodies; D060185:Tetraspanin 24