Diamond‐blackfan anemia: The role of immunoglobulin blocking factor in remission

Abstract

AbstractSome patients with Diamond‐Blackfan syndrome may have suppressor T‐cells responsible for the failure of normal erythropoiesis. The capacity of Diamond‐Blackfan syndrome mononuclear cells to react in mixed leukocyte culture to the stimulus of nucleated red cells was tested using bone marrow as the cell source. In all but one instance, Diamond‐Blackfan mononuclear cells and cells from normal or a multiply‐transfused control showed similar degrees of stimulation. Patient mononuclear cells reacted normally to phytohemagglutinin (PHA). The presence of a cytotoxic effect of Diamond‐Blackfan mononuclear cells on normal nucleated red cells was examined using a 59Fe‐release assay. There was no evidence for lymphocyte‐mediated erythroid cytotoxicity. Immunoglobulins (Ig) were removed from Diamond‐Blackfan serum by affinity chromatography. Erythroid burst‐forming units (BFU‐E) failed to grow normally in Ig‐depleted patient autologous serum, but growth failure was reversed when Ig eluted from the affinity column was added back to the culture. Diamond‐Blackfan Ig added to autologous mononuclear cells in the absence of autologous serum normalized colony growth. T‐cells of some Diamond‐Blackfan syndrome patients may suppress BFU‐E growth, but they do not react abnormally in mixed leukocyte culture to nucleated erythroid cells and are not cytotoxic for erythroblasts under our conditions of study. The serum‐blocking factor in our patients appears to be an Ig that promotes BFU‐E generation despite the presence of suppressor T‐cells. Although it cannot be proved, this may be related to the remission of disease in our patients.