Biomedical subjects
Publications and source records attributed to J Groth.
Anti-IgG autoantibodies are reported to possess immunoregulatory properties. In the present study, we investigated the effect of pretransplant serum IgG-anti-F(ab')2gamma autoantibody activity on kidney graft outcome in recipients from two transplant centers.
In our effort to find an optimum immunosuppressive protocol for kidney transplantation we introduced two forms of ATG prophylaxis: 1. high-dose single-bolus prophylaxis (9 mg/kg) in non-sensitized patients (PRA < 5%); and 2. low-dose 8-day prophylaxis (1.5-3.0 mg/kg) in sensitized patients (PRA > 5%). A total of 204 kidney graft recipients were included in this study and treated with a triple-drug therapy (TDT). In comparison with TDT-treated controls, in sensitized patients the 8-day ATG prophylaxis resulted in a reduced rate of rejection episodes (25.5% vs 47%), an improved 1-year graft survival (82% vs 71%) and patient survival (94% vs 90%). In non-sensitized patients the high-dose single-bolus ATG prophylaxis induced a T-cell lymphopenia lasting 4 to 5 days and, in comparison with the corresponding controls, resulted in a shortened hospital stay (31.2 days vs 36.7 days), a reduced rate of rejection episodes (25.5% vs 53%), an improved 1-year graft survival (92% vs 86%) and patient survival (100% vs 94%).
Pretransplant sera of 474 kidney graft recipients were tested for IgG-anti-F(ab')2 gamma activity. The patients had significantly higher IgG-anti-F(ab')2 gamma activity than healthy controls (P = 0.0004). Serum lymphocytotoxic antibodies were correlated with IgG-anti-F(ab')2 gamma (P = 0.004), whereas CMV infection and blood transfusions were not. We found a significant association between pretransplant IgG-anti-F(ab')2 gamma activity and early and 1-year kidney graft outcome. This association was pronounced in recipients with no lymphocytotoxic antibodies. Recipients with immediately functioning grafts and a creatinine < 130 mumol/L at 1 year had strikingly higher pretransplant IgG-anti-F(ab')2 gamma activity than patients with graft failure (P < 0.0001).
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A commercially available plasma expander (Gelifundol) containing 5.5% oxypolygelatine in buffered saline was used instead of serum as a supplement for freezing several types of human cell and a mouse myeloma cell line in liquid nitrogen. Viability, recovery, proliferation and cytotoxic activity were compared after freezing with a plasma expander and after conventional freezing with human AB serum or fetal calf serum. The plasma expander proved to be equivalent or superior to AB serum by all parameters tested and acceptable even when compared with fetal calf serum. Furthermore, this preparation is cheap, sterile, free of BSE, viral and mycoplasmal contamination or antibodies and foreign serum proteins. We therefore recommend it for freezing of cells for culture of HLA typing.
Between 1980 and 1986 465 cadaveric kidney transplants were performed at the Kidney Transplant Centre Berlin-Friedrichshain. The post-transplant risk to acquire a cytomegalovirus (CMV) infection depended on the preoperative CMV antibody status of donor and recipient, on the nettoimmunosuppression and on the recipient's age. The highest infection rate and the most serious courses showed seronegative recipients from seropositive donors. The typical time interval of clinical manifestation included the postoperative months 1-3. A significant dependence of the frequency of infection on different immunosuppressive protocols could not be proven. But there was a significant coincidence between CMV infection and rejection crises. In spite of the raised frequency of rejection crises an influence of the CMV infection on the 1-year-graft and patient survival rates could not be demonstrated. Both an early diagnosis and an adequate therapy are of particular importance.
A cohort of children diagnosed at age seven as suffering from deficits in attention, motor control and perception was compared at age 13 with a group of children without such problems. More than two-thirds of the index children no longer had any clearly detectable motor problems at 13, but they still had significantly prolonged complex reaction times. These results suggest that children with these deficits in the early school years have a fair biological prognosis by the early teen years.
The excretion capacity of 24 kidney allografts which had been dialyzed because of non-function was examined. It has been shown that only 4 out of 24 allografts (16.7%) were truly without function. All other transplants did show a slight or more improvement of the excretion capacity prior to irreversible loss of graft function. As a cause the non-identified graft rejection is discussed.
Twenty retransplant patients were serially screened for donor-reactive antibodies (DRA). DRA appeared exclusively in patients whose grafts permanently failed and these DRA shared some common features, namely early appearance (days 4-8 post-transplant), high titers (1:10 up to more than 1:400), and broad anti-HLA specificity. This preliminary data would suggest that regrafted patients with primary graft failure represent a distinct subgroup of particularly immune responsive individuals.
We used the strength of suppression of the interleukin-1-induced peak CRP response (CRPmax) post-transplant as a measure for the individual steroid susceptibility in vivo. This suppressive effect proved to be fully reversible after abrogation of steroid therapy following graft removal. The standardized suppressive therapy immediately post-transplant led to extremely different results in individual patients ranging from no suppression (26.1% of the patients) to a strong or practically absolute suppression of CRP synthesis in 20.7% of the patients studied. This behaviour is also reflected in anti-rejection bolus therapy whereby the percentage of prednisolone resistant patients strongly correlated with increasing (unsuppressed) CRPmax values. From our data we conclude that the disparate anti-inflammatory susceptibility for corticosteroids seems to be an individual feature of patients under high-dose steroid treatment.
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Enhancing alloantiserum was produced by immunizing male BD IX inbred rats with density gradient separated nylon-wool adherent spleen lymphocytes from male rats of the major histocompatibility complex (MHC) different inbred strain Sprague-Dawley (SD). Long-term surviving (BD IX X SD) F1 to BD IX kidney grafts were achieved by treating the recipients with 1 ml alloantiserum at the time of transplantation. After greater than 100 days 7 passively enhanced F1 kidneys were retransplanted into naive BD IX rats. Four out of 7 secondary recipients, producing only low levels of lymphocytotoxic antibodies, survived for greater than 100 days, 3/7 rats died of surgical or infection complications. Twenty-one naive BD IX recipients of normal F1 kidneys were treated with serum (1 ml i.v.) and/or spleen lymphocytes (1 X 10(7) i.v.) obtained from the long-term survivors. An indefinite graft survival was achieved in 13 out of 21 rats. After greater than 150 days 6 out of these 13 passively enhanced F1 kidneys were retransplanted into naive BD IX rats which were challenged at the time of grafting with 4 X 10(7) SD lymphocytes to elicit rejection. Six out of 6 kidneys survived greater than 150 days. Thus, the long-term survival of rat kidney allografts in this model is associated with a strong reduction of graft immunogenicity as well as the development of suppressor cells and enhancing antibodies.
In 32 healthy adults between 20 and 50 years, the number of theophylline-resistant T-lymphocytes (T-res) was determined to be 51 +/- 4% or 1,161 +/- 326 per microliter, and that of theophylline-sensitive T-lymphocytes (T-sens), 11 +/- 2% or 252 +/- 95.--The decrease in number of rosette-forming cells after incubation with 1 mM theophylline was not caused by reduced vitality (51Cr-release test). The testing of various theophylline concentrations (1, 3, 5, and 10 mM) did not result in a changed count of T-sens. By a variation of the lymphocyte: sheep erythrocyte ratio and of incubation temperature it was found that T-sens possess high-affine and T-res low-affine receptors for sheep erythrocytes. While about 30% of the cells of both subpopulations proved to have Fc-IgM-receptors, among T-sens a significantly higher number of cells carried Fc-IgG-receptors than among T-res (29% vs. 10%).
At different intervals (2, 4, 8, 12 and 21 days) after preimmunization of BD IX inbred rats with density gradient-separated nylon-wool-adherent spleen lymphocytes from rats of the MHC different inbred strain Sprague-Dawley, (BD IX X SD)F1 kidneys were transplanted into the immunized BD IX rats. The non-immunized control rats died after 11-16 days. Kidneys transplanted 8 or 12 days after preimmunization survived indefinitely without any signs of rejection. In contrast, the rats grafted 2 and 4 days after preimmunization showed elevated levels of blood urea nitrogen (mean: 70-83 mmol/l) on the 7th post-operative day. The transplantation on day 21 resulted in a slight rejection episode on the 7th postoperative day. These results suggest the efficacy of nylon-wool-adherent lymphocytes in inducing an active transplant protection.
In 75 patients after kidney transplantation during the whole stay in hospital after operation the serum concentration of C-reactive protein (CRP) was determined serially and quantitatively as well as all the urines were investigated with regard to the appearance of a CRP-uria. We succeeded in proving CRP in the urine in a high percentage (67%) in transplants which never functioned and in a smaller extent (25%) during the postoperative renal failure. For the diagnostic ascertainment of the rejection crises as well as for the estimation of the effectiveness of the antirejection therapy with high doses of prednisolone the daily CRP serum control is a valuable contrivance. The judgement of the CRP-values should always be performed together with the other data received by laboratory investigations as well as also with the clinical data.
The appearance, specificity and dynamics of donor reactive antibodies have been studied in 9 patients who experienced early irreversible graft failure. In 5 out of 9 patients we were able to detect donor reactive antibodies. Their reaction patterns may be ascribed to a common responder type ("high responder"). Diagnostic and preventive possibilities for preventing early irreversible graft failures have been discussed.
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In the peripheral blood of healthy adults the number of theophylline-resistant T-lymphocytes (T-res) is 51 +/- 4% and 1,161 +/- 326/microliter, respectively, and the number of theophyllins-sensitive 11 +/- 2% and 252 +/- 95/microliters. The membrane markers show a heterogeneous distribution. The quotient from T-res/T-sens is 4.9 +/- 1.3. Within the T-sens 14% are CD4+ and 30% CD8+, 29% carry Fc-IgC and 34% Fc-IgM-receptors. Thus the T-res in their netto-function were helper cells and the T-sens suppressor/cytotox cells. Before the transplantation the preoperative ratio of the two subpopulation is significantly diminished (Q = 3.66 +/- 1.53), however, prognostic statements cannot be deduced from this. Activations of the immune system (rejection crises, cytomegalovirus infections) are accompanied by significant diminutions of the T-sens, whereby the T-res/T-sens-Quotient increases. Thus they are unequivocally included into immunoregulatory processes.