Successful Retreatment of Allograft Rejection With Okt3

Mr, First; Tj, Schroeder; Pe, Hurtubise; Me, Mansour; Penn, Israel; Munda, R; Wf, Balistreri; Jw, Alexander; Db, Melvin; Jp, Fidler

doi:10.1097/00007890-198901000-00020

Cited by 40 publications

(5 citation statements)

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“…Several studies have shown that the majority of patients (>70%) with low antibody titres measured by ELISA experienced rever sal of rejection after muromonab CD3 re-treatment. [245][246][247] Howe ver, the ELISA method does not distingui sh between anti-idiotype and anti-i sotyp e antibodies, is difficult to standardise, and is cumbersome to perform on small numbers of samples.l21 9.222] Other assays, such as the immunofluorescence inhibition test, [244] flow cytometry, [248] and a new membrane-based Irnmunoassay.t-t" aim to improve the selective detection of anti-idiotypic antibodies and maintain ease of performance. The membranebased immunoassay was compared with the ELISA: the result s for the 2 methods correlated well, [249] although the only strong advantage of the membrane-based method over the ELISA was the rapid turnaround time of 15 minute s for the former.…”

Section: Anti-muromonab Cd3 Antibody Monitoringmentioning

confidence: 99%

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

Tsunoda

Aweeka

1996

Clinical Pharmacokinetics

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Most experience of the therapeutic drug monitoring of immunosuppressive agents has been acquired in the field of solid organ transplantation; however, agents such as cyclosporin (cyclosporin A) are being increasingly utilised for the management of autoimmune diseases. Cyclosporin is the most widely studied immunosuppressant, but in spite of this many controversies still exist as to the optimum strategy for monitoring this drug. Owing to its widely variable pharmacokinetics and metabolism, and the absence of a simple method to measure therapeutic effectiveness, many factors should be considered. In most circumstances, measuring whole blood through concentrations of cyclosporin with a specific assay methodology is warranted. In addition, knowledge of other factors that may alter the pharmacokinetics (such as liver function, concomitant food or medications, gastrointestinal status, and time since transplantation) should be taken into account so that therapy can be appropriately adjusted. Other methods of monitoring have been investigated, such as AUC (area under the concentration-time curve) monitoring and immunological monitoring. However, further refinement of these techniques and greater experience with their efficacy must be accumulated before their role in the monitoring of cyclosporin can be defined. Tacrolimus, like cyclosporin, shares many of the difficulties in monitoring for efficacy and toxicity due largely to the variable pharmacokinetics; similarly to cyclosporin, whole blood through concentration monitoring should be utilised in combination with knowledge of the factors that may affect the pharmacokinetics. Muromonab CD3 (OKT3) is a monoclonal antibody used for the treatment and prophylaxis of acute allograft rejection. Several immunological monitoring techniques have been investigated for this agent. Monitoring CD3+ levels can assist clinicians in determining therapeutic efficacy, while measuring antimuromonab CD3 antibody titres can help determine if xenosensitisation has occurred, causing therapeutic ineffectiveness. The clinical monitoring of azathioprine, one of the first immunosuppressive agents used in transplantation, has historically been limited to monitoring complete blood counts for bone marrow suppression. However, newer techniques measuring intracellular DNA nucleotides appear to be promising. The new immunosuppressants on the horizon include mycophenolate mofetil and rapamycin. The clinical experience with therapeutic drug monitoring of these 2 compounds is scant in the literature; however, both agents have demonstrated efficacy in preventing or treating allograft rejection while maintaining a relatively well tolerated toxicity profile in recent clinical trials. Routine monitoring does not appear to be warranted for immunosuppressive therapy in autoimmune diseases.

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Section: Anti-muromonab Cd3 Antibody Monitoringmentioning

confidence: 99%

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

Tsunoda

Aweeka

1996

Clinical Pharmacokinetics

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“…The oFBMAb 1H5 described in this paper begins to inhibit complement activation at concentrations as low as 1 ,ug/ml. This level is clinically achievable, as it is similar to the concentrations of mouse IgG in serum seen with the antirejection drug OKT3 (16). A potential limiting factor in the treatment of humans with any mouse IgG would be the presence of preformed human antibodies to mouse IgG, which would prevent the development of any therapeutic concentration in serum.…”

Section: Discussionmentioning

confidence: 75%

Complement activation by whole endotoxin is blocked by a monoclonal antibody to factor B

Clardy

1994

Infect Immun

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Sepsis is both a common and, despite present-day therapy, a serious disease. The pathophysiology of the septic response is a complex, multifactorial phenomenon which in part involves the activation of complement by bacterial endotoxin. A monoclonal antibody to human complement factor B, code-named lH5, which was capable of specifically inhibiting the alternative pathway of complement activation at concentrations as low as 1 ,ug/ml, is described. This agent had no effect on the classical pathway of complement activation. It was capable of preventing the activation of complement by even high concentrations (0.1 mg/ml) of whole endotoxin; however, it was ineffective in preventing activation of complement by endotoxin derived from a * Corresponding author. Mailing address: Rush-Presbyterian-St.

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“…The rate of infection and the incidence of lymphoproliferative disorder are noted to be even higher after repeated application of antilymphocytic agents (23–26). Development of human antihorse or human antimouse antibodies against ALG or OKT3 further limits repeated courses of antilymphocyte induction therapy (27, 28).…”

Section: Discussionmentioning

confidence: 99%

The use of daclizumab as induction therapy in combination with tacrolimus and mycophenolate mofetil in recipients with previous transplants

Ciancio

Mattiazzi²,

Roth

et al. 2003

Clinical Transplantation

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Clinical trials using daclizumab as induction therapy in combination with tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in solid organ transplantation. In an attempt to obtain a low rejection rate we proceeded with the use of daclizumab as induction therapy, in combination with TAC and MMF for recipients with previous transplants. In this study, we analyzed patients who received previous transplants, treated with the above immunosuppressive regimen. Group A consisted of four patients with previous liver transplants, group B consisted of 16 recipients with previous kidney transplants and group C consisted of three patients with previous simultaneous pancreas-kidney transplants. All patients underwent cadaveric kidney transplants except one patient in group B, who underwent a pancreas transplant. At 12 months, patient and graft survival for all groups was 100 and 100%, respectively. Acute rejection rate was 0% for group A, 12.5% for group B, and 0% for group C. Daclizumab induction therapy is effective for patients with previous transplants and does not appear to increase the risk of acute rejection.

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Successful Retreatment of Allograft Rejection With Okt3

Cited by 40 publications

References 0 publications

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

The Use of Therapeutic Drug Monitoring to Optimise Immunosuppressive Therapy

Complement activation by whole endotoxin is blocked by a monoclonal antibody to factor B

The use of daclizumab as induction therapy in combination with tacrolimus and mycophenolate mofetil in recipients with previous transplants

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