Composition of the intra-erythroblastic precipitates in thalassaemia and congenital dyserythropoietic anaemia (CDA): identification of a new type of CDA with intra-erythroblastic precipitates not reacting with monoclonal antibodies to alpha- and beta-globin chains.
Ultrathin sections of bone marrow cells from two patients with homozygous beta-thalassaemia, two patients with haemoglobin H (HbH) disease, a patient with congenital dyserythropoietic anaemia (CDA) type III and two patients with severe congenital dyserythropoietic anaemia of an unusual type were reacted with mouse monoclonal antibodies against various globin chains and the reaction visualized using a gold-labelled goat antibody against mouse IgG. The multiple rounded intra-erythroblastic inclusions found in homozygous beta-thalassaemia reacted with the monoclonal antibody against alpha-globin chains but not beta-globin chains, thus confirming that they consisted of precipitated alpha-globin chains. The branching intra-erythroblastic inclusions found in HbH disease and CDA type III reacted with the monoclonal antibody against beta-globin chains but not alpha-globin chains, indicating that they consisted of precipitated beta-globin chains. The two patients with severe CDA had been transfusion-dependent since infancy, had a normal alpha:beta globin chain synthesis ratio or parents with normal red cell indices, displayed prominent dysplastic changes in their erythroblasts, and had intra-erythroblastic inclusions resembling those seen in homozygous beta-thalassaemia. However, unlike those in beta-thalassaemia, the inclusions in these two patients did not react with the monoclonal antibody against either alpha- or beta-globin chains. The inclusions reacted with antibody against zeta-globin chains, but detailed studies in one of the patients indicated that the antigen involved was not zeta-globin. These patients have features not reported in the condition known as dominantly inherited inclusion body beta-thalassaemia and appear to suffer from a novel type of CDA in which the intra-erythroblastic inclusions may consist of some non-globin protein or structurally-abnormal alpha-globin chains.
Wickramasinghe
S N
SN
Department of Haematology, Imperial College School of Medicine at St Mary's, London, U.K.
Lee
M J
MJ
Furukawa
T
T
Eguchi
M
M
Reid
C D
CD
D000742:Anemia, Dyserythropoietic, Congenital / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000378:metabolism; D002675:Child, Preschool; D004900:Erythroblasts / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005914:Globins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008297:Male; D008854:Microscopy, Electron; D017085:alpha-Thalassemia / Q000097:blood*; D017086:beta-Thalassemia / Q000097:blood*
D000911:Antibodies, Monoclonal; D005914:Globins