title: Low-dose rabbit antithymocyte globulin induction therapy results in prolonged selective lymphocyte depletion irrespective of maintenance immunosuppression.
abstract: Rabbit antithymocyte globulin therapy (rATG) is a potent lymphocyte-depleting agent commonly used following renal transplantation to reduce the risk of acute rejection. Standard doses (7-10 mg/kg) of rATG result in profound lymphopenia and predispose patients to infection and malignancy. The effects of lower doses of rATG (LoD-rATG, 3-5 mg/kg) on peripheral blood lymphocytes (PBL) are as yet unknown. In this prospective clinical trial, PBL subsets were characterized by flow cytometry over 12 months following LoD-rATG therapy. All patients were initially treated with standard doses of tacrolimus, mycophenolic acid, and prednisone. At 3 months, patients were randomized to either lower doses of tacrolimus or sirolimus to examine the effects of maintenance immunosuppression on PBL reemergence. LoD-rATG therapy resulted in prolonged suppression of CD19+ B cells, total CD3+ T cells, as well as naïve and memory CD4+ T cell and CD4/CD25/Foxp3+ T-regulatory subsets irrespective of chronic immunosuppressive therapy. Selective depletion was only noted in the CD4CD45RA+ naïve T-cell subset resulting in an altered memory/naïve CD4+ ratio. LoD-rATG failed to deplete CD8+ T cells, which increased their relative contribution to the total CD3+ pool. All other lymphocyte subsets maintained near normal proportions. Thus, LoD-rATG therapy may lessen the adverse effects of full dose rATG while maintaining overall efficacy.
authors: Department of Surgery, State University of New York, University at Buffalo, Buffalo General Hospital, Kaleidahealth, Buffalo, New York 14203, USA. opankewycz@kaleidahealth.org
authors: O
authors: O
authors: Pankewycz
authors: N
authors: N
authors: Leca
authors: R
authors: R
authors: Kohli
authors: P K
authors: PK
authors: Wallace
authors: M
authors: M
authors: Said
authors: L
authors: L
authors: Feng
authors: M
authors: M
authors: Alnimri
authors: S
authors: S
authors: Patel
authors: M R
authors: MR
authors: Laftavi
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000166:cytology; D008214:Lymphocytes / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011817:Rabbits; D012306:Risk; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018941:Antigens, CD19; D000961:Antilymphocyte Serum; D017252:CD3 Complex; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007166:Immunosuppressive Agents; D053645:Interleukin-2 Receptor alpha Subunit