Low-dose rabbit antithymocyte globulin induction therapy results in prolonged selective lymphocyte depletion irrespective of maintenance immunosuppression
Copyright © 2011 Elsevier Inc. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2011 |
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| Erschienen: |
2011 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Transplantation proceedings - 43(2011), 2 vom: 10. März, Seite 462-5 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pankewycz, O [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 22.07.2011 Date Revised 16.11.2017 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.transproceed.2011.01.034 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM206983328 |
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| 245 | 1 | 0 | |a Low-dose rabbit antithymocyte globulin induction therapy results in prolonged selective lymphocyte depletion irrespective of maintenance immunosuppression |
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| 520 | |a Copyright © 2011 Elsevier Inc. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Clinical Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
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| 700 | 1 | |a Kohli, R |e verfasserin |4 aut | |
| 700 | 1 | |a Wallace, P K |e verfasserin |4 aut | |
| 700 | 1 | |a Said, M |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, L |e verfasserin |4 aut | |
| 700 | 1 | |a Alnimri, M |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, S |e verfasserin |4 aut | |
| 700 | 1 | |a Laftavi, M R |e verfasserin |4 aut | |
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