Heavy transfusions and presence of an anti-protein 4.2 antibody in 4.2(-) hereditary spherocytosis (949delG)

Background and Objectives. 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 pa tient had long suffered from a gastric ulcer and impaired liver function. H e had had several dramatic episodes of gastrointestinal tract bleeding and had received numerous transfusions. An antibody against a high frequency, u ndefined antigen was found, creating a transfusional deadlock. We elucidate d the responsible mutation and searched for an anti-protein 4.2 antibody. Design and Methods. Red cell membranes were analyzed by SDS-PAGE and by Wes tern blotting. Nucleotide sequencing was performed after reverse transcript ase-polymerase chain reaction (RT-PCR) and nested PCR. Results. The not previously described mutation was a single base deletion: 949delG (CGC-->CC, exon 7, codon 317) in the homozygous state. It was calle d protein 4.2 Nancy. The deletion placed a nonsense codon shortly downstrea m so that no viable polypeptide could be synthesized. The patient carried a strong antibody against protein 4.2 as shown by western blotting. Interpretation and Conclusions. The manifestations resulting from the mutat ion described were compared with the picture of HS stemming from other ELB4 2 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 patie nt. (C) 2000, Ferrata Storti Foundation.