Heavy transfusions and presence of an anti-protein 4.2 antibody in 4. 2(-) hereditary spherocytosis (949delG).
OBJECTIVE
A patient with hereditary spherocytosis (HS) was found not to have red cell membrane protein 4.2. This rare form of HS, or 4.2 (-) HS, stems from mutations within the ELB42 or the EPB3 genes. The patient had long suffered from a gastric ulcer and impaired liver function. He had had several dramatic episodes of gastrointestinal tract bleeding and had received numerous transfusions. An antibody against a high frequency, undefined antigen was found, creating a transfusional deadlock. We elucidated the responsible mutation and searched for an anti-protein 4.2 antibody.


METHODS
Red cell membranes were analyzed by SDS-PAGE and by Western blotting. Nucleotide sequencing was performed after reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR.


RESULTS
The not previously described mutation was a single base deletion: 949delG (CGCAECC, exon 7, codon 317) in the homozygous state. It was called protein 4.2 Nancy. The deletion placed a non-sense codon shortly downstream so that no viable polypeptide could be synthesized. The patient carried a strong antibody against protein 4.2 as shown by Western blotting.


CONCLUSIONS
The manifestations resulting from the mutation described were compared with the picture of HS stemming from other ELB42 gene mutations. We discuss the mechanism through which the anti-protein 4.2 antibody developed. There was no way to establish or to rule out whether the antibody participated in the transfusional deadlock found in our patient.
Beauchamp-Nicoud
A
A
INSERM U 473, 84 rue du Général-Leclerc, 94276 Le Kremlin-Bicêtre, France. delaunay@kb.inserm.fr.
Morle
L
L
Lutz
H U
HU
Stammler
P
P
Agulles
O
O
Petermann-Khder
R
R
Iolascon
A
A
Perrotta
S
S
Cynober
T
T
Tchernia
G
G
Delaunay
J
J
Baudin-Creuza
V
V
D000328:Adult; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000276:immunology; D001798:Blood Proteins / Q000235:genetics* / Q000276:immunology*; D015153:Blotting, Western; D003598:Cytoskeletal Proteins; D004252:DNA Mutational Analysis; D004910:Erythrocyte Membrane / Q000737:chemistry; D005192:Family Health; D016368:Frameshift Mutation; D006471:Gastrointestinal Hemorrhage / Q000209:etiology / Q000628:therapy; D006720:Homozygote; D006801:Humans; D007106:Immune Sera; D007518:Isoantibodies / Q000097:blood*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology; D011817:Rabbits; D006178:Romani People / Q000235:genetics; D013049:Spectrin / Q000276:immunology; D013103:Spherocytosis, Hereditary / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D065227:Transfusion Reaction
D001457:Anion Exchange Protein 1, Erythrocyte; D001798:Blood Proteins; D003598:Cytoskeletal Proteins; D007106:Immune Sera; D007518:Isoantibodies; D008565:Membrane Proteins; C044791:erythrocyte membrane band 4.2 protein; D013049:Spectrin