OKT3 first-dose reaction: Association with T cell subsets and cytokine release

OKT3 first-dose reaction: Association with T cell subsets and cytokine release

OKT3 first-dose reaction: Association with T cell subsets and cytokine release. Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is...

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Bibliographic Details
Published in:Kidney international Vol. 39; no. 1; pp. 141 - 148
Main Authors: Gaston, Robert S., Deierhoi, Mark H., Patterson, Trudie, Prasthofer, Edward, Julian, Bruce A., Barber, W. Henry, Laskow, David A., Diethelm, Arnold G., Curtis, John J.
Format: Journal Article
Language:English
Published: New York, NY Elsevier Inc 01-01-1991
Nature Publishing
Subjects:
Adult
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - therapeutic use
Biological and medical sciences
Drug toxicity and drugs side effects treatment
Female
Flow Cytometry
Graft Rejection - immunology
Humans
Immunosuppression
Immunosuppressive Agents - therapeutic use
Interferon-gamma - immunology
Interleukin-2 - immunology
Kidney Transplantation - immunology
Male
Medical sciences
Miscellaneous (drug allergy, mutagens, teratogens...)
Muromonab-CD3
Pancreas Transplantation - immunology
Pharmacology. Drug treatments
T-Lymphocyte Subsets - immunology
Tumor Necrosis Factor-alpha - immunology
Human
Flow cytometry
Immunomodulation
Toxicity
Cytokine
Transplantation
Monoclonal antibody
Cell subpopulation
Kidney
Treatment
Interleukin 2
Immunotherapy
T-Lymphocyte
Tumor necrosis factor α
Release
Gamma interferon
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Summary:OKT3 first-dose reaction: Association with T cell subsets and cytokine release. Use of the monoclonal antibody OKT3 to prevent or treat allograft rejection has become commonplace. Its administration is often complicated by serious side effects, usually occurring within one to two hours after OKT3 is given, and is termed first-dose reaction. The mechanism underlying these signs and symptoms is poorly defined, but may be related to cytokine release Twenty-three kidney or kidney/ pancreas transplant recipients received OKT3 as treatment of acute rejection. Signs and symptoms occurring after the first dose were observed and quantitated prospectively, and a reaction score was calculated. Blood was drawn immediately before, and at 2 and 24 hours after the first dose of OKT3 for determination of interleukin-2 (IL2), interferon-gamma (IFNγ), and tumor necrosis factor-alpha (TNFα) levels, and flow cytometric analysis of T cell subsets. Two groups were defined based on severity of first-dose reaction. Group 1 patients (N = 11) had very mild reactions (reaction score ≤ 3); Group 2 patients (N = 12) had more severe reactions (score ≥ 5). All patients demonstrated a significant rise in serum TNFa from baseline to two hours after OKT3 (9 ± 3 pg/ml to 378 ± 54 pg/ml, P < 0.0001), and there was significant correlation between reaction scores and two-hour TNFa levels (P = 0.005). Group 2 patients had higher TNFa levels at two hours than did Group 1 patients (484 ± 75 pg/ml vs. 263 ± 62 pg/ml, P = 0.04). Levels of IL2 and IFNγ were not elevated at any sampling time. Group 2 patients also had significantly greater numbers of circulating CD3+ (521 ± 114 vs. 257 ± 58, P = 0.04) and CD4+ (226 ± 45 vs. 87 ± 23, P = 0.01) lymphocytes prior to OKT3 administration. In addition, pre-OKT3 CD4+ levels correlated with reaction scores. These data implicate TNFα, perhaps of activated T lymphocyte origin, as a key mediator of the OKT3 first-dose reaction.
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content type line 23
ISSN:0085-2538
1523-1755
DOI:10.1038/ki.1991.18