Monitoring of T-cell subsets in patients treated with anti-CD 25 antibody.
Daclizumab and basiliximab, the antibodies to the interleukin-2 receptor (anti-IL-2R), decrease the incidence of acute rejection in renal transplantation. However, prolonged blockade of IL-2 receptor (IL-2R:CD25) may hamper apoptosis of reactive T-cell clones and thus may obstruct tolerance induction. We determined the effect of varying doses of anti-IL-2R on the number of CD3+CD25+ cells as an index of CD 25 blockade. The number of CD3+CD25+ cells was determined in four groups of induction therapies: no antibody induction; two doses of 50 or 25 mg daclizumab on day 0 and day 14; and two doses of 20 mg basiliximab at day 0 and day 4 (n=10, 24, 10, and 10, respectively). The number of CD3+CD25+ cells were monitored in whole blood before antibody infusion as well as 24 hours thereafter and weekly after transplantation. With two doses of 50 mg daclizumab, two doses of 25 mg daclizumab, and two doses of 20 mg basiliximab, the expression of CD3+CD25+ cells was completely suppressed for 12, 10, and 12 weeks posttransplantation, respectively. The reappearance of CD3+CD25+ cells above the baseline for each induction regimen was: 17 weeks for two doses of 50 mg daclizumab, 11 weeks for two doses of 25 mg daclizumab, and 13 weeks for two doses of 20 mg basiliximab. Monitoring of CD3+CD25+ cells may be utilized to tailor anti-IL-2R administration at a minimal dosage, yet retaining adequate IL-2R blockade for at least 3 months posttransplantation.
Praditpornsilpa
K
K
Division of Nephrology, Faculty of Medicine, Chulalongkorn University Hospital, Bangkok, Thailand.
Avihingsanon
Y
Y
Kupatawintu
P
P
Songpanich
S
S
Pisitkul
T
T
Kansanabuch
T
T
Eiam-Ong
S
S
Chusil
S
S
O-Charoen
R
R
Tungsanga
K
K
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD / Q000097:blood; D001379:Azathioprine / Q000627:therapeutic use; D000077552:Basiliximab; D017252:CD3 Complex / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use; D000077561:Daclizumab; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors* / Q000097:blood; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015703:Antigens, CD; D017252:CD3 Complex; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D016572:Cyclosporine; D000077552:Basiliximab; D000077561:Daclizumab; D001379:Azathioprine