Antibodies to glycosylphosphatidyl-inositol anchored proteins (GPI-AP) in antithymocyte and antilymphocyte globulin: possible role for the expansion of GPI-AP deficient cells in aplastic anemia.
Antithymocyte globulin (ATG) and antilymphocyte globulin (ALG) are currently used successfully for immunosuppressive treatment of aplastic anemia. In this study we have investigated whether commercial ATG/ALG preparations contain antibodies against glycosylphosphatidyl-inositol anchored proteins (GPI-AP), which could be responsible for emergence of GPI-deficient populations in aplastic anemia after ATG/ALG therapy. We analyzed four commercial ATG/ALG preparations by competitive binding assays using flow cytometry. Quantification was achieved by calculating the concentration of ATG/ALG required to give 50% inhibition of binding the specific fluorochrome-labeled monoclonal antibody (EC50). High concentrations of antibodies against the GPI-anchored protein CD52 were found in all preparations (Lymphoglobulin Genzyme, Thymoglobulin Genzyme, ATGAM. Pharmacia & Upjohn, and ATG-Fresenius S Fresenius). Antibodies against the GPI-anchored protein CD48 are present in significant concentrations except in the preparation ATGAM. CD16 antibodies were found in lower concentrations. We could not detect significant concentrations of antibodies against the GPI-anchored proteins CD157 and CD14. Campath-1H, a monoclonal antibody against the GPI-anchored protein CD52, has been used as immunosuppressive tool for T-cell depletion. CD52 antibodies in ATG/ALG preparations might contribute in the same way to the immunosuppressive effects in treatment of aplastic anemia. It is known that in a substantial proportion of patients with aplastic anemia GPI-deficient cells are present in a low level at diagnosis or emerge after immunosuppressive therapy. GPI-anchored antibodies in ATG/ALG preparations might lead to a relative advantage for pre-existing GPI-deficient cells caused by an escape from the antibody-mediated attack.
Breitinger
Heike H
HH
Institut für Transfusionsmedizin, Universität Ulm und Institut für Klinische Transfusionsmedizin und Immungenetik Ulm Gemeinnützige GmbH, Ulm, Germany.
Rojewski
Markus T
MT
Schrezenmeier
Hubert
H
D000741:Anemia, Aplastic / Q000276:immunology / Q000628:therapy; D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000961:Antilymphocyte Serum / Q000276:immunology / Q000627:therapeutic use; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000276:immunology*
D000906:Antibodies; D000961:Antilymphocyte Serum; D017261:Glycosylphosphatidylinositols; D007166:Immunosuppressive Agents; D008565:Membrane Proteins