A novel form of congenital dyserythropoietic anemia associated with
deficiency of erythroid CD44 and a unique blood group phenotype [In(a-b- ),
Co(a-b-)]
SF Parsons, J Jones, DJ Anstee, PA Judson, B Gardner, E Wiener, J Poole, N Illum and SN Wickramasinghe
International Blood Group Reference Laboratory, Bristol, UK.
We have used a panel of well-characterized monoclonal antibodies (MoAbs) to
examine the blood cells of a patient with a novel form of congenital
dyserythropoietic anemia (CDA) characterized by intra- erythroblastic and
intra-erythrocytic membranous inclusions. Twelve antibodies defining three
nonoverlapping epitope groups on the extracellular domain of CD44 all
failed to react with the red blood cells (RBCs) of the patient. A rabbit
antibody to the cytoplasmic domain of CD44 from normal RBCs failed to react
with the patient's RBC ghosts. In contrast, the patient's lymphocytes,
granulocytes, and monocytes showed apparently normal CD44 expression. Bone
marrow preparations stained with CD44 antibodies and visualized with 125I
antimouse Ig (F(ab')2) followed by autoradiography showed positive staining
of lymphocytes and myeloid cells but not of most orthotolidine- positive
erythroblasts. The patient's RBCs also gave weaker than normal reactions
with MoAbs of anti-LWab specificity while MoAbs to glycophorins A, B, and
C, Rh polypeptides, CD47, CD55, CD58, CD59, acetylcholinesterase, and
Lutheran and Kell glycoproteins all gave normal reactions. Agglutination
tests with human blood grouping sera demonstrated that the RBCs of the
patient have the unique phenotype In(a-b-), Co(a-b-) and that they also
lack the high incidence RBC antigen AnWj. The phenotype In(a-b-) would be
expected because these antigens are known to be expressed on CD44. There is
also some evidence associating the AnWj antigen with CD44. However, the CO
blood group locus is on chromosome 7p whereas that for CD44 is on
chromosome 11p. Quantitative binding assays using 125I-labeled Fab
fragments of CD44 antibodies did not show any evidence for reduced levels
of CD44 on RBCs from the parents of the patient or from her unaffected
sister. The parents and sister had the common Colton blood group phenotype
[Co(a+b- )]. Neither deficiency of CD44 nor absence of Colton antigens are
general features of CDA because erythrocytes from patients with CDA I, CDA
II, CDA III, and two other unclassified CDAs had normal expression of CD44
and normal Colton blood group phenotypes. Further analysis of the defect(s)
present in the patient's erythroid cells may provide useful information
regarding membrane assembly and the regulation of differentiation in normal
erythroid cells.
Volume 83,
Issue 3,
pp. 860-868,
02/01/1994
Copyright © 1994 by The American Society of Hematology
