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 α- and β-globin chains

Ultrathin sections of bone marrow cells from two patients with homozygous β-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 β-thalassaemia reacted with the monoclonal antibody against α-globin chains but not β-globin chains, thus confirming that they consisted of precipitated α-globin chains. The branching intra-erythroblastic inclusions found in HbH disease and CDA type III reacted with the monoclonal antibody against β-globin chains but not α-globin chains, indicating that they consisted of precipitated β-globin chains. The two patients with severe CDA had been transfusion-dependent since infancy, had a normal α :β 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 β-thalassaemia. However, unlike those in β-thalassaemia. the inclusions in these two patients did not react with the monoclonal antibody against either α- or β-globin chains. The inclusions reacted with antibody against (-globin chains, but detailed studies in one of the patients indicated that the antigen involved was not ζ-globin. These patients have features not reported in the condition known as dominantly inherited inclusion body β-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 α-globin chains.