title: A "new" road to tolerance: clonal deletion and drugs added when needed (DAWN).
abstract: We propose clonal deletion--immunization followed by deletion--as a "new" way to achieve tolerance. Immunization of a donor results in specific stimulation of a clone of cells, which can then be killed by various agents, leaving the patient otherwise immunologically normal. The theory of clonal deletion is supported by experimental evidence as well as earlier experiences with kidney transplants and donor-specific transfusions. To date, 22 patients who underwent clonal deletion have been surviving for 1.5 to 2.5 years with only low-dose prednisone. In addition, those patients who required conventional immunosuppressive drugs were treated with the new Drugs Added When Needed (DAWN) protocol. With DAWN as a tactic ready for intervention, and by using antibodies to monitor the completeness of clonal deletion, we assure that patients are subjected to the minimal amount of drugs on a personalized basis. We suggest that risks involved in testing this new procedure are small and the benefits immeasurable.
authors.affiliation: Terasaki Foundation Laboratory, Los Angeles CA, USA.
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
authors.forename: Mathew L
authors.initials: ML
authors.lastname: Everly
authors.forename: Hugo
authors.initials: H
authors.lastname: Kaneku
authors.forename: Junichi
authors.initials: J
authors.lastname: Hoshino
authors.forename: Aruna V
authors.initials: AV
authors.lastname: Vanikar
authors.forename: Himanshu V
authors.initials: HV
authors.lastname: Patel
authors.forename: Pankaj R
authors.initials: PR
authors.lastname: Shah
authors.forename: H L
authors.initials: HL
authors.lastname: Trivedi
mesh_terms: D000818:Animals; D017637:Clonal Deletion / Q000187:drug effects*; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006801:Humans; D007114:Immunization; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016377:Organ Transplantation / Q000009:adverse effects*; D023001:Transplantation Tolerance / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents