Assuntos
Antígenos CD/sangue , Soro Antilinfocitário/uso terapêutico , Transplante de Rim/imunologia , Depleção Linfocítica , Anticorpos Monoclonais , Imunofluorescência , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêuticoAssuntos
Muromonab-CD3/sangue , Muromonab-CD3/uso terapêutico , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Antígenos CD/análise , Ensaio de Imunoadsorção Enzimática/métodos , Citometria de Fluxo/métodos , Humanos , Depleção Linfocítica , Linfócitos/imunologia , Monitorização Imunológica/métodos , Muromonab-CD3/farmacologiaAssuntos
Anticorpos Monoclonais/sangue , Transplante de Coração/imunologia , Imunoglobulina G/sangue , Imunossupressores/farmacocinética , Transplante de Rim/imunologia , Linfócitos/imunologia , Anticorpos Monoclonais/farmacologia , Antígenos CD4/metabolismo , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Transplante de Coração/fisiologia , Humanos , Imunoglobulina G/farmacologia , Imunossupressores/farmacologia , Transplante de Rim/fisiologiaAssuntos
Antígenos de Diferenciação de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/imunologia , Anticorpos Monoclonais/imunologia , Reações Antígeno-Anticorpo , Antígenos de Diferenciação de Linfócitos T/análise , Soro Antilinfocitário/imunologia , Complexo CD3 , Endocitose , Citometria de Fluxo , Humanos , Terapia de Imunossupressão/métodos , Técnicas In Vitro , Transplante de Rim/imunologia , Muromonab-CD3 , Transplante de Pâncreas/imunologia , Receptores de Antígenos de Linfócitos T/análiseRESUMO
Thirty-one pediatric patients with acute renal allograft rejection were treated with the monoclonal antibody OKT3. In 24 cases, increased doses of steroids followed by a polyclonal antithymocyte globulin were ineffective in reversing the rejection episode. Twenty-eight patients completed the prescribed minimum 10-day treatment course, with effective rejection reversal in 22. Three patients failed to complete the course of therapy: one because of leukopenia that developed after the first dose, one because of a clotted graft, and another because of symptomatic cytomegalovirus infection. The overall success rate of OKT3 for rejection reversal was 74%; however, 55% of recipients had rebound rejection, and 85% of patients had detectable anti-OKT3 antibodies after completion of the course of therapy. Ten patients were treated with a second course of OKT3, and in eight of these patients, rejection was at least temporarily reversed. The starting dose of OKT3 for second-course therapy was the same as that used during first-course therapy, but in five cases the dose was increased during the course because of inadequate therapeutic response. Seven of these patients lost their grafts a mean of 6.5 months after completion of second-course therapy. We looked for anti-OKT3 antibody in nine recipients after completion of a second treatment course and found it in all nine. Our observations regarding a second treatment course with this monoclonal antibody preparation suggest that although rejection reversal may be observed, ultimate graft survival is poor and anti-OKT3 antibody formation is enhanced.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/imunologia , Transplante de Rim/imunologia , Acetaminofen/uso terapêutico , Adolescente , Anticorpos Anti-Idiotípicos/análise , Anticorpos Monoclonais/administração & dosagem , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Soro Antilinfocitário/uso terapêutico , Azatioprina/uso terapêutico , Complexo CD3 , Criança , Pré-Escolar , Difenidramina/uso terapêutico , Humanos , Imunoglobulina A , Lactente , Metilprednisolona/uso terapêutico , Prednisona/uso terapêutico , Receptores de Antígenos de Linfócitos T/análise , Recidiva , Linfócitos T/imunologiaRESUMO
A second course of OKT3 monoclonal anti-T cell antibody was given to 21 recipients of kidney transplants. Rejections reversed in 43% of patients in whom 95% of rejections had reversed with their initial OKT3 course. Reversal was highly dependent upon the timing of rejection, anti-OKT3 antibody production, and T cell CD3 modulation. Rejections treated greater than 90 days after transplantation were resistant to OKT3 reversal. High-titer anti-OKT3 antibodies prevented OKT3 reversal of rejection, and effective CD3 (the cell surface target of OKT3) modulation was necessary for successful OKT3 reversal of rejection. Reexposure to OKT3 further stimulated anti-OKT3 antibody production and broadened the specificity of the antibodies produced. OKT3 can effectively and safely be used a second time for treatment of early T cell-mediated renal allograft rejections if high-titer anti-OKT3 antibodies have not been made.