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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 127 records · Page 7Linked to original sources
PubMed1995

Efficacy of rejection prophylaxis with OKT3 in renal transplantation. Collaborative Transplant Study.

The results of renal cadaver transplants performed between 1984 and 1994 and reported to the Collaborative Transplant Study were analyzed to examine the effect of rejection prophylaxis with OKT3. OKT3 prophylaxis with sequential (i.e., delayed) addition of cyclosporine (CsA), compared with immunosuppressive treatment that included CsA but not OKT3, resulted in a significantly higher overall 3-year graft survival rate in recipients of first transplants (75 +/- 1% vs. 71 +/- 1%, respectively; P < 0.0001) and in recipients of retransplants (68 +/- 2% vs. 62 +/- 1%, respectively; P < 0.001). In contrast, the simultaneous administration of OKT3 and CsA from the first posttransplant day did not result in improved graft survival over treatment with CsA alone. Graft survival rates were significantly associated with matching for HLA-A, -B, and -DR antigens in both first and retransplant recipients treated with a sequential protocol of OKT3/CsA (P < 0.01). Among patients with preformed panel reactive lymphocytotoxic antibodies > 50%, significantly better 3-year graft survival rates were obtained with sequential OKT3/CsA than were achieved without OKT3 in first transplant recipients (80 +/- 5% vs. 63 +/- 1%, respectively; P < 0.001) and in retransplant recipients (73 +/- 5% vs. 58 +/- 1%, respectively; P < 0.01). Significantly improved 3-year graft survival rates with OKT3 and sequential CsA were likewise obtained in two other groups of high-risk patients: black recipients (P < 0.001) and pediatric recipients (P < 0.01). The results demonstrate an advantage for OKT3 prophylaxis in conjunction with delayed CsA therapy among renal transplant recipients at high immunological risk, particularly among presensitized patients.

Black People↗
PubMed1995

Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation.

In mice, retrovirus-associated breast cancers are promoted by immune mechanisms, and immunosuppression during the premalignant phase reduces the incidence of breast cancer and prolongs life. If some women likewise have immune promotion of breast cancer, the incidence of breast cancer in patients receiving therapeutic immunosuppression should be lower than that in a comparable cohort of non-immunosuppressed women. We examined the incidence of de-novo breast cancer arising in women receiving immunosuppressive therapy after kidney or heart transplantation, comparing the figures with published rates. In 25,914 immunosuppressed women followed for 1-11 years there were 86 cases of breast cancer compared with 113.8 expected (p = 0.009). Incidence was particularly low in the first transplant year with relative risk 0.49, rising to 0.84 in subsequent years. For all other major cancers the incidence was higher in the immunosuppressed women. If, as in mice, the reduced incidence of breast cancer is a direct effect of immunosuppression, these observations raise the possibility of therapeutic manipulation of specific immune mechanisms that promote tumour growth.

Adult↗
PubMed1995

[Immunological aspects of kidney transplantation in Switzerland 1981-1992. Swiss Transplant Work Group Kidney Transplantation].

Every year some 200-260 kidney transplants are performed in Switzerland, improving the quality of life of patients with end stage renal disease. The current organ shortage is delaying transplantation of the 400 patients on the waiting list, a situation which calls for optimal utilization of the available donor kidneys. It is well established that AB0-compatibility, negative cytotoxic crossmatch, and optimal immunosuppressive therapy including cyclosporin A are important for a favorable clinical outcome. To identify further factors influencing transplant outcome, we undertook a retrospective study of all 1656 transplants to which the above criteria applied. We defined transplants matched for at least 1A, 1B, and 1DR HLA antigen as the better matched, and the remainder as the less well matched grafts. In patients who were not or only weakly immunized to alloantigens, the 5-year graft survival probability was 0.78 versus 0.69 for the better versus the less well matched transplants (p < 0.005). The strongly immunized patients did not, however, show a significant association between the degree of HLA matching and graft survival, presumably because there were more immunized patients in the HLA matched group. As expected, the patients previously immunized to alloantigens showed significantly reduced graft survival early after transplantation. Positive CMV serology, sex mismatch, and cold ischemia time did not correlate with graft survival. Compared to results obtained in the USA or Germany, the survival time of donor kidneys transplanted in Switzerland was significantly increased. Factors contributing to the good results in Switzerland are discussed. Future goals are reduction of alloimmunization and optimized HLA compatibility.

Cyclosporine↗
PubMed1995

Striking inverse correlation between IgG anti-F(ab')2 and autoantibody production in patients with cold agglutination.

Previous experiments showed that the physiologic IgG anti-F(ab')2 antibody suppresses the response of human autoreactive B cells. In the present study, we analyzed the IgG anti-F(ab')2 antibody in 293 patients with cold agglutination (CA). Their average IgG anti-F(ab')2 titer was not much different (211 +/- 8.3) from that of 279 healthy persons (195 +/- 6.7). However, CA patients with high anti-F(ab')2 titers had low CA autoantibody titers and vice versa (P = .0028; rho = -0.175). The stratification of patients according to the auto-antibody's specificity (anti-I, anti-i, anti-Pr) showed an inverse correlation between anti-F(ab')2 and CA in the anti-I group (P = .0057; rho = -0.180). Interestingly, the association was present only in patients whose disease was caused by noninfectious agents (P < .0001; rho = -0.423). The inverse correlation argues for an important role of the IgG anti-F(ab')2 in the regulation of autoantibody production in CA patients.

Agglutinins↗
PubMed1995

In vitro cytokine treatment of B cell defects in HIV-infected hemophilia patients.

HIV-infected patients exhibit defects in B cell differentiation and in the IL-6 response of B cells, in association with autoantibody formation against T cells. These autoantibodies have been implicated as important factors in the development of immunodeficiency disease. As the restoration of defective B cell responses might prevent autoantibody formation and the resulting immunosuppression, we studied whether in vitro treatment with recombinant IL-2 (rIL-2), recombinant IL-4 (rIL-4) or recombinant IL-6 (rIL-6) might restore the response of B cells of HIV-infected patients. B cells of 6 HIV-negative hemophilia patients, 4 HIV-positive patients at CDC stage II, III, 4 HIV-positive patients at CDC stage IV, and 6 healthy controls were tested in Staphylococcus aureus Cowan I (SAC-I)-stimulated B cell cultures and Pokeweed mitogen (PWM)-stimulated allogeneic B and T cell cocultures. B cell differentiation was assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG and IL-6 in culture supernatants. In vitro application of rIL-6 resulted in suppression of both elevated unstimulated and mitogen-stimulated B cell responses in a dose-dependent manner which was in part due to feedback inhibition. PWM- and SAC-I-stimulated IgG and IgM responses, respectively, could be restored after addition of 10 U/ml rIL-2 in HIV-negative patients, but not in HIV-positive patients. Addition of rIL-4 to cultures resulted in suppression of both unstimulated and mitogen-stimulated IL-6 secretion and B cell responses. Severely depressed B cell responses in CDC IV patients were not significantly affected by cytokine application. These results indicate that defective Ig responses in HIV-negative patients may be restored by rIL-2 treatment whereas HIV-induced B cell defects are not corrected by supply of T cell help or cytokines promoting B cell growth and differentiation.

Autoantibodies↗
PubMed1995

[Cellular immune defect caused by postoperative irradiation in patients with squamous epithelial carcinomas of the upper aerodigestive tract].

The effect of locoregional postoperative radiation therapy on cellular immunity was investigated in 11 patients with head and neck cancer. During the course of the radiation therapy, total lymphocyte counts, CD8+ lymphocyte counts and especially CD4+ lymphocyte counts decreased significantly. The mean CD4+ lymphocyte counts dropped from 739/microliters to 183/microliters (p < 0.001) and the average CD4+/CD8+ ratio also decreased significantly. In addition all patients showed impaired in vitro lymphocyte stimulation responses to several mitogens, with reductions found to be 10% to 50% of normal responses. Within 3-4 weeks after radiation therapy there was a slight increase of CD4+ lymphocyte counts and the in vitro lymphocyte stimulation responses showed a tendency to normalization. These results indicate that locoregional postoperative radiation therapy in patients with head and neck cancer can induce a severe impairment of cellular immunity.

CD4 Lymphocyte Count↗
PubMed1995

Influence of treatment with cyclosporine, azathioprine and steroids on chronic allograft failure. The Collaborative Transplant Study.

The efficacy of different immunosuppressive regimens was analyzed in a multicenter series of cadaver kidney transplants reported to the Collaborative Transplant Study. Induction therapy with steroid-free cyclosporine regimens resulted in significantly better graft survival than induction including a combination of cyclosporine and steroids (P < 0.001) or azathioprine and steroids (P < 0.0001). Because immunosuppressive protocols frequently changed during the first post-transplant year, graft survival from the first to the fifth year was used to analyze the efficacy of long-term maintenance immunosuppressive regimens. Steroid-free maintenance with cyclosporine resulted in significantly better five-year graft survival (P < 0.0001) and patient survival (P < 0.01) than maintenance with steroid-containing cyclosporine regimens or maintenance on azathioprine and steroids without cyclosporine (P < 0.0001). Steroid-free patients received significantly higher doses of cyclosporine than patients on steroid-containing cyclosporine regimens. These results suggest that steroid-free maintenance immunosuppression with cyclosporine should be attempted in patients with an uncomplicated posttransplant course.

Azathioprine↗