Direct binding of antithymoctye globulin to haemopoietic progenitor cells in aplastic anaemia.
Antithymocyte globulin (ATG) is widely used in the treatment of aplastic anaemia (AA) and a response occurs in 60-80% of patients. However, its exact mechanism of action in the treatment of AA has yet to be determined. Previously, we have shown that ATG increases colony growth from purified bone marrow CD34+ cells of AA patients in vitro, and decreases stem cell apoptosis and the expression of soluble Fas receptor after ATG therapy in vivo. The aim of this study was to further examine the association of ATG with AA haemopoietic progenitor cells. We describe here that ATG bound directly to CD34+ cells. Forty-six patients and 20 normal control subjects were studied. ATG bound to CD34+ cells in normal control subjects (mean 90.38%) as determined by flow cytometry. The mean percentage of CD34+ cells binding to ATG was 59.90% in untreated aplastic patients, 83.24% in partial responders, 58.3% in non-responders and 62.73% in relapsed patients. In completely recovered patients, ATG binding was indistinguishable from control subjects. The functionality of AA patients' haemopoietic progenitor cells was assessed using colony assays. These results demonstrate the direct binding of ATG to CD34+ cells and suggest that differences in its binding to AA CD34+ cells could reflect functional differences in the haemopoietic stem cell compartment throughout the disease process.
Flynn
Julie
J
Department of Haematology, St George's Hospital Medical School, London, UK. j.flynn@sghms.ac.uk
Cox
Charlotte V
CV
Rizzo
Sian
S
Foukaneli
Theodora
T
Rice
Katherine
K
Murphy
Matthew
M
Welsh
Jonathan
J
Rutherford
Theodora R
TR
Gordon-Smith
Edward C
EC
Gibson
Frances M
FM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy*; D018952:Antigens, CD34 / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000378:metabolism / Q000627:therapeutic use*; D016022:Case-Control Studies; D002648:Child; D003114:Colony-Forming Units Assay; D005260:Female; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011485:Protein Binding
D018952:Antigens, CD34; D000961:Antilymphocyte Serum