Use of OKT3 monoclonal antibody as induction therapy for control of rejection in liver transplantation

This report details a single center's experience with OKT3 induction immunosuppression for liver transplantation. One hundred ninety-nine consecutive, unselected adult liver recipients received OKT3 therapy for 9–10 days combined with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two patients (26.1%) experienced 57 episodes of acute rejection. The median time of onset of rejection was 18 days after grafting. Seventy-eight percent of the rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and the need for OKT3 retreatment was infrequent. One year actuarial graft and patient survival was 79.7% and 82.3% respectively. Based on this evidence, it appears that OKT3 prophylaxis provides good control of acute rejection with a very low incidence of recurrent rejection.     

Reactive oxygen product formation after Fcγ receptor-mediated neutrophil activation by monomeric mouse IgG2a: implications for the generation of first dose effects after OKT3 treatment

In the present study, we provide evidence that IgG2a monoclonal antibody (mAb) OKT3 is able to induce reactive oxygen intermediate (ROI) formation in polymorphonuclear leukocytes (PMN) when FcγRIIIB as well as FcγRII are bound concomitantly. Inhibition of binding to either FcγR by specific mAb (3G8 or IV. 3, respectively) resulted in complete abrogation of the OKT3-induced respiratory burst. The effect of OKT3 was independent from its specificity and thus also from its T cell-activating property, since nonbinding IgG2a isotype controls induced similar amounts of ROI. The IgG2b mAb BMA031 as well as the respective nonbinding isotype control were only minimally effective. With regard to the potential role of PMN activation in inflammation and tissue damage, our findings offer an extended explanation for the generation of initial adverse reactions to OKT3. Thus, one might speculate that the concerted action of cytokines liberated after its administration, what may lead to margination of leukocytes, and activation of PMN via FcγR might produce first-dose reactions to OKT3 by directing radical-mediated damage against the endothelium.     

Correlation between active E-rosettes and antigens defined on peripheral lymphocytes by OKT 4 and OKT 8 monoclonal antibodies

A relationship has been sought between the classical marker, active E-rosette and the surface antigens of T-lymphocytes, defined by OKT 4 and 8 monoclonal antigens, in the peripheral blood of normal human people. It was found that no significant correlation existed in the case of OKT 4 antigen; conversely the OKT 8-positive cells were significantly enriched after E-rosette-forming cell isolation (about 2.5 times in comparison with the negatively selected cells). In this latter case, some partial correlation could exist between SRBC-high affinity of T-lymphocytes and the subsets defined by OKT 8 antigen.     

肿瘤病人外周血T细胞及其亚群和NK细胞活性变化的研究

一般认为,T细胞和NK细胞可能是构成机体肿瘤免疫功能的重要因素。肿瘤病人外周血T细胞及其亚群和NK细胞活性的变化,国内外均有报道。但对同一肿瘤病人T细胞及其亚群和NK细胞活性变化的对比研究报道得较少。本文用OKT系列的单克隆抗体检测T细胞及其亚群,用~(51)Cr-释放试验检测NK细胞活性,对同一肿瘤病人外     

Successful treatment of transfusion-associated graft-versus-host disease

Summary. We present an immunocompetent patient with transfusion-associated graft-versus-host disease (GVHD), in which chimaerism of peripheral blood lymphocytes was demonstrated by analysis of a highly polymorphic genome. The patient was treated successfully with anti-CD 3 monoclonal antibody, OKT3 and cyclosporin A. Although it is undoubtedly important to prevent transfusion-associated GVHD by irradiation of cellular blood components, intensive therapy with OKT3 and cyclosporin A in the early phase of onset may be effective for treatment of this potentially fatal condition. The mechanism of the effectiveness of this treatment for transfusion-associated GVHD is discussed.     

Incidence of Malignancies in Patients Treated With Sirolimus Following Heart Transplantation

BackgroundMalignancy is a major cause of late post-heart transplantation (HT) mortality. Sirolimus (SRL) exerts antiproliferative properties and its long-term use in HT as primary immunosuppression (IS) is associated with decreased mortality risk that is not fully explained by attenuation of cardiac allograft vasculopathy progression.ObjectivesThis study sought to examine whether conversion from calcineurin inhibitor (CNI)-based to SRL-based IS was associated with decreased risk of malignancy post-HT.MethodsOverall, 523 patients underwent HT between 1994 and 2016 at a single institution. The main outcomes included incidence of overall de novo malignancies (excluding non-melanoma skin cancers [NMSCs]), post-transplantation lymphoproliferative disorders (PTLD), and first and subsequent primary occurrences of NMSC post-HT.ResultsThe study identified 307 patients on SRL-based and 216 on CNI-based maintenance IS. Over a median follow-up of 10 years after HT, overall de novo malignancies (non-NMSC) occurred in 31% of CNI patients and in 13% of SRL patients (adjusted hazard ratio [HR]: 0.34; 95% confidence interval [CI]: 0.18 to 0.62; p < 0.001). The incidence of the first NMSC was similar in the SRL and CNI groups (HR: 0.92; 95% CI: 0.66 to 1.28; p = 0.62). However, conversion to SRL was significantly associated with a decreased risk of subsequent primary occurrences of NMSC compared with that of CNI (adjusted HR: 0.44; 95% CI: 0.28 to 0.69; p < 0.001). The adjusted PTLD risk was significantly decreased in the SRL group (HR: 0.13; 95% CI: 0.03 to 0.59; p = 0.009). Late survival post-HT was markedly decreased in patients who developed non-NMSC, PTLD, or non-PTLD compared with patients who did not develop these malignancies, whereas NMSC had no significant effect on survival.ConclusionsConversion to SRL was associated with a decreased risk of all de novo malignancies, PTLD, and subsequent primary occurrences of NMSC after HT. These findings provided further explanation of the late survival benefit with long-term SRL use.