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G Opelz

Publications and source records attributed to G Opelz.

At least 145 records · Page 8Linked to original sources
PubMed1995

Clinical implications from studies of HLA antigens in idiopathic nephrotic syndrome in children.

HLA class I and II antigen frequencies were determined in two large cohorts of children with idiopathic nephrotic syndrome (NS) from Southwest France (n = 199) and Southwest Germany (n = 152) and compared with unrelated healthy individuals from the same geographical areas. Strength of HLA association was expressed by the relative risk (RR) estimated by Odd's ratio. We examined 105 steroid-resistant and 242 steroid-sensitive NS patients who were subdivided in non-relapsers, infrequent relapsers and frequent relapsers or steroid-dependent patients. In steroid-sensitive patients significant associations were found with HLA-DR7 (RR 5.1 in French, 3.2 in Germans), -DQ2 (RR 4.7/2.3) and with the phenotypic combination HLA-DR3/DR7 (RR 5.6/7.7). Significant negative associations were encountered with HLA-DR2, -DR6 and -DQ1. The associations were stronger in frequent relapsers/steroid-dependent patients than in infrequent relapsers and were not significant in non-relapsers. In steroid-resistant patients the only significant association found was with the combined occurrence of HLA-DR3/DR7. We propose that in childhood NS tissue typing for selected HLA class II antigens is helpful in prediciting the clinical course.

Adolescent↗
PubMed1994

Effect of the maintenance immunosuppressive drug regimen on kidney transplant outcome.

Renal transplant recipients require long-term maintenance immunosuppression for prevention of graft rejection. To reduce harmful side effects, combinations of immunosuppressive drugs are used. The effect on long-term outcome of different drug regimen has not been established. Over 12,000 kidney recipients who initially received triple-drug immunosuppressive therapy (cyclosporine, steroids, and azathioprine) after transplantation were studied. Graft and patient survival rates were analyzed over a 5-year period in relation to the 1-year immunosuppressive regimen. Five-year graft survival was significantly higher in 1270 patients who were changed from triple-drug therapy to steroid-free maintenance with cyclosporine (with or without the addition of azathioprine) (87 +/- 1%) than in 8024 patients who remained on triple-drug therapy (76 +/- 1%, P < 0.0001), 2829 patients on cyclosporine and steroids (79 +/- 1%, P < 0.0001), and 830 patients on steroids and azathioprine (63 +/- 2%, P < 0.0001). Patient survival was also significantly higher in patients on steroid-free maintenance (P < 0.0001). Steroid-free patients received significantly higher doses of cyclosporine than patients on regimens containing steroids (P < 0.0001). The immunosuppressive maintenance protocols that are currently most widely used appear to give suboptimal results. We suggest that discontinuation of steroid therapy should be attempted in renal transplant recipients after they have experienced several months of stable graft function on triple-drug immunosuppression.

Azathioprine↗
PubMed1994

Complement activation by recombinant HIV-1 glycoprotein gp120.

The mechanism of CD4+ cell depletion in HIV-infected patients is poorly understood. In this study we investigated whether rgp120 can activate the complement system in the absence of anti-gp120 Abs. We found that the complement proteins C4, C3d, C5b-9, and properdin bind to rgp 120-coated CD4+ T cells of healthy individuals when incubated in autologous serum. Activation of the complement system occurred primarily via the classical pathway and was abolished in sera deficient in C1q and C4 as well as in the presence of EDTA. No cell lysis was observed in a lymphocytotoxicity assay using human serum, possibly because of homologous restriction of complement lysis. In contrast, addition of rabbit sera induced lysis of the rgp 120-precoated cells. Cell lysis by rabbit serum was found to be because of naturally occurring IgM anti-gp 120 Abs. The rgp 120, which was immobilized on the surface of microtiter plates activated complement in the absence of lymphocytes. Complement activation by cell-bound HIV-1 envelope glycoprotein gp120 with subsequent opsonization may be relevant for the elimination of noninfected CD4+ T cells in HIV-infected patients.

Amino Acid Sequence↗
PubMed1994

Association of IgA-anti-Fab autoantibodies with disease stage in head-and-neck cancer.

Patients with head-and-neck cancer commonly have immune defects. It was reported that these patients have raised serum IgA levels. We investigated whether IgA-anti-Fab autoantibodies, which occur in association with immune dysfunction, are present in patients with head-and-neck cancer. Sera of 101 patients with squamous-cell carcinoma (SCCHN) and 8 patients with adenoid cystic carcinoma (ACCHN) of the head and neck were tested in ELISA for IgA-anti-Fab autoantibody activity. IgA-anti-Fab serum activity was significantly higher in both SCCHN and ACCHN patients than in healthy controls. In patients with SCCHN, an association between disease stage and IgA-anti-Fab activity was established. Stage-IV patients had significantly higher IgA-anti-Fab than stage-I patients or healthy controls. Stage-II and stage-III patients had intermediate levels. Extremely high IgA-anti-Fab activity was observed in 7 patients who died within 6 months following testing, suggesting a relationship of autoimmunity with terminal disintegration of physiological body functions. IgA-anti-Fab autoantibodies may explain the occurrence of immune defects in patients with head-and-neck cancer.

Adult↗
PubMed1994

The influence of HLA compatibility on graft survival after heart transplantation. The Collaborative Transplant Study.

BACKGROUND: In cardiac transplantation, it is standard practice for donor hearts to be allocated to recipients without consideration of the extent of HLA matching. Because the HLA system is highly polymorphic, the likelihood that donor hearts will be well matched to their recipients by chance alone is extremely small. It has therefore not been possible in the past to analyze adequately the success rate of transplantation with HLA-matched hearts. METHODS: We initiated a collaborative study in 1985 to evaluate the influence of HLA compatibility on graft survival in heart transplantation. Data were collected from 104 centers in 24 countries. RESULTS: Of the 8331 patients, 128 received a graft with no HLA-A, B, or DR mismatches or only one mismatch. This frequency (1.5 percent) corresponds to the rate that would be expected from a random allocation of donor organs. The three-year rate of graft survival correlated strongly with HLA compatibility, decreasing from a mean (+/- SE) of 83 +/- 4 percent for the 128 donor hearts with no mismatches or only one mismatch to 76 +/- 2 percent for the 439 hearts with two mismatches and 71 +/- 1 percent for the 7764 hearts with three to six mismatches (P < 0.001). Multifactorial Cox regression analysis showed that this effect was independent of the age and sex of the donor and recipient, the type of underlying disease, the duration of cold ischemia, and the use of prophylaxis with antilymphocyte antibodies (P = 0.005). CONCLUSIONS: Graft survival in heart transplantation is significantly influenced by the extent of HLA compatibility.

Adolescent↗
PubMed1994

Comparative study of antibodies that are associated with disease progression in HIV disease.

Two types of antibodies which previously were found to be inversely associated with CD4+ cell counts and which may contribute to the progression of HIV disease were measured in parallel in 55 serum samples of 7 longitudinally tested HIV-infected patients (4 homosexual men, 3 haemophilic men) and in 15 serum samples from 15 patients with advanced AIDS. HIV-infection enhancing antibodies were determined in the presence of near-physiologic human complement concentration using a complement receptor type 2 (CR2) carrying HIV-target cell line. IgG and IgA class autoantibodies directed against human IgG-Fab fragments were measured in specific ELISA assays. In agreement with our previous studies obtained in HIV-seropositive haemophilic patients, significant negative correlations were found between CD4+ cell counts and IgG anti-Fab and IgA anti-Fab antibodies (Spearman correlation coefficient r = -0.587, P < 0.0001; and r = -0.269, P = 0.024, respectively). A significant positive correlation was observed between complement-dependent enhancing antibodies and IgA anti-Fab antibodies (r = 0.408, P = 0.003), whereas the correlation with IgG anti-Fab antibodies was only weak (r = 0.288, P = 0.034). Serum samples with high titres of complement-dependent enhancing antibodies had almost 3 times higher IgA anti-Fab autoantibody activity than sera with low titres (P = 0.0038). Our findings indicate that the two disease markers in HIV disease, enhancing antibodies and autoantibodies directed against the Fab moiety of IgG, are not identical. However, anti-Fab antibodies may contribute to complement-dependent HIV infection enhancement.

Acquired Immunodeficiency Syndrome↗
PubMed1994

IL-6 independent monocyte/B cell defect in renal transplant recipients with long-term stable graft function.

We showed previously that the B cell response in renal transplant recipients with long-term stable graft function (ST patients) is significantly affected by T suppressor activity. To further assess the role of the monocyte/B cell compartment in B cell regulation, we tested B cell responses in 30 ST patients (> 1 year after transplant) and 15 patients with chronic rejection (CR patients). PWM was used for T cell-dependent B cell stimulation in an allogeneic coculture system, and SAC I for T cell- and monocyte-independent B cell stimulation. B cell responses were assessed in a reverse hemolytic plaque assay and by ELISA determination of IgM, IgG, and IL-6 in culture supernatants. In PWM-stimulated cultures of ST patients, we found a diminished immunoglobulin-secreting cell (ISC) formation (P < 0.0001 and P < 0.05, compared with controls and CR patients, respectively) and diminished IgM secretion (P = 0.06 and P < 0.01, respectively), whereas CR patients and controls were not significantly different. Two of 35 (6%) controls and 3 of 15 (20%) CR patients, in contrast to 20 of 30 (67%) ST patients, displayed defective ISC formation (P < 0.0001). This defective B cell response may be the result of reduced CD36+ monocyte counts in ST patients (P < 0.005), as PWM-stimulated B cell responses and CD36+ cell counts were significantly associated (P < 0.05, ISC and IgM response). A role of monocytes in the impairment of B cell function is further supported by decreased plasma neopterin levels in ST compared with CR patients (P = 0.0001), a significant association between plasma neopterin and PWM-stimulated B cell responses (P < 0.05, ISC response; P = 0.0001, IgM response), and by the finding that B cell responses in ST patients after monocyte-independent stimulation with SAC I were unaffected. ST and CR patients showed no significant differences in B cell subsets, plasma IL-6, or IL-6 responses of mitogen-stimulated cultures. Our data indicate that an IL-6-independent monocyte or B cell defect plays a role in the maintenance of stable transplant function.

Adult↗
PubMed1994

HLA class II associations with idiopathic nephrotic syndrome in children.

The occasional familial occurrence of idiopathic nephrotic syndrome (NS) points to a genetic predisposition. Reports on associations with certain HLA class II antigens support this hypothesis. In order to define the immunogenetic background of NS more precisely, HLA class II allele frequencies in 161 children with NS were studied by restriction fragment length polymorphism (RFLP) typing. The patient cohorts consisted of 87 children from Southwest-France and 74 from Southwest-Germany. The control group consisted of 118 French and 101 German unrelated individuals from the same geographical areas. HLA alleles were defined in patients with steroid-sensitive (SS) and steroid-resistant (SR) NS and in controls. RFLP typing revealed that the previously reported association between SSNS and HLA-DR7 is confined to the RFLP split 7.1 (DRB1*07) with a combined relative risk (RRcomb) of 6.2. HLA-DQB typing showed an increased frequency of the allele DQB2b (DQB1*0201) (RRcomb = 7.8). HLA-DQA typing showed an association of SSNS with DQA3 (DQA1*0201,0301,0302) (RRcomb = 4.1). The highest RR (16.5) for SSNS was found in German patients who carried the two DRB1 specificities 17.1 (DRB1*0301) and 7.1 (DRB1*07). All associations were stronger in SS patients with frequent relapses or steroid dependency than in non- or infrequent relapsers. SR patients exhibited no significant associations with HLA class II alleles.

Alleles↗
PubMed1994

Isotypes and IgG subclasses of anti-Fab antibodies in human immunodeficiency virus-infected hemophilia patients.

We reported recently that anti-Fab autoantibodies of the IgG isotype are associated with the decrease of helper/inducer (CD4+) lymphocytes in human immunodeficiency virus-infected (HIV+) hemophilia patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC). In the present study we investigated the subclass distribution of IgG-anti-Fab autoantibodies, and whether anti-Fab antibodies of the IgA and IgM isotypes also are associated with the development of AIDS. Sera of HIV+ patients with AIDS had significantly higher IgA-anti-Fab activity than HIV+ patients with ARC (p < 0.02), HIV+ patients without AIDS/ARC (p < 0.0001), HIV-negative (HIV-) patients (p < 0.001), or healthy controls (p < 0.0001). An inverse association was found between IgA-anti-Fab activity and CD4+ cell counts (r = -0.396, p < 10(-6)). In contrast, no association of CD4+ cell counts was observed with IgM-anti-Fab. However, IgM-anti-Fab was significantly increased in patients with thrombocytopenia. We found a significant association between IgA-anti-Fab activity and serum neopterin concentrations (r = 0.310, p < 10(-5)). IgG-anti-Fab activity was detected mainly in the IgG3 fraction, although in HIV+ patients with AIDS/ARC various IgG subclasses were present. Affinity-purified anti-Fab antibodies isolated from sera of AIDS patients bound to rgp120-preincubated CD4+ cells of a healthy individual, supporting our hypothesis that anti-Fab antibodies and free circulating gp120 molecules are involved in the elimination of uninfected CD4+ cells. Removal of anti-Fab autoantibodies from the circulation by immune adsorbance might be a useful approach in the treatment of AIDS.

AIDS-Related Complex↗
PubMed1994

A prospective, randomized trial of pretransplant blood transfusions in cadaver kidney transplant candidates. Leuven Collaborative Group for Transplantation.

To assess the effect of pretransplant blood transfusions on the outcome of cadaveric kidney transplantation, a single-centre analysis was performed of 171 patients randomly assigned to receive no pretransplant transfusion (n = 85) or to receive at least three random blood transfusions (n = 86). After transfusion 18 of the latter patients developed circulating lymphocytotoxic T-cell antibodies, but the sensitization was only transient. At the time of transplantation, none was still sensitized. In both groups 60 patients have been transplanted. Patient and graft survival rates were significantly higher in the transfused group than in the non-transfused group. In the non-transfused patients the higher mortality was due to complications related to repeated anti-rejection therapy. Non-transfused patients had more repeated acute rejection episodes than the transfused patients. The present study indicates that pretransplant blood transfusions still facilitate graft acceptance even in the setting of good HLA matching and with cyclosporine as the basic immunosuppressant. The risk of sensitization is very low.

Adult↗
PubMed1994

Non-Hodgkin's lymphoma after kidney or heart transplantation: frequency of occurrence during the first posttransplant year.

The incidence of non-Hodgkin's lymphoma was analysed in over 70,000 kidney transplant recipients and over 10,000 heart, heart-lung or lung transplant recipients. An increased incidence of lymphomas during the first posttransplant year was observed in cadaver kidney recipients as compared to related kidney recipients, in thoracic organ recipients as compared to kidney recipients, in heart-lung recipients as compared to heart or lung recipients, in patients transplanted in North America as compared to patients transplanted in Europe, in patients receiving cyclosporine in combination with azathioprine as compared to patients with other immunosuppressive regimens, and in patients receiving ATG/ALG or monoclonal OKT3 for rejection prophylaxis.

Germany↗
PubMed1994

A method for HLA-DQA typing by the PCR-SSP technique.

There is preliminary evidence that matching for HLA-DQ is important for kidney graft survival. We developed a method for HLA-DQA typing based on the PCR-SSP principle. The procedure consisted of three steps: DNA isolation, PCR amplification and visualization of the PCR product under UV light. For the identification of all currently known DQA1 alleles, we designed 18 different primers that allowed typing for the specificities DQA1*0101, *1012, *0103, *0104, *0201, *03, *0401, *0501 and DQA1*0601. For the typing of a single individual, 12 PCR mixes were needed, each containing a primer pair specific for a certain allele group, and a pair of control primers that amplified a non-polymorphic region. The time required for this procedure was approximately 3 h from the time of blood collection. Comparison of this method with DQA typing by the RFLP method in 151 individuals revealed only a single discrepancy. The method can be easily applied for prospective cadaver donor typing.

DNA Primers↗
PubMed1994

Comparison of serological and DNA HLA-DR typing results for transplantation in Western Europe, Eastern Europe, North America and South America.

In a previous study, DNA typing revealed that 25% of serological HLA-DR typings of kidney transplants were incorrect. In the current study, we analyzed whether this error rate had improved in recent years, and whether there were differences according to geographical region. From 1988 to 1991 the error rate of serological typing improved slightly in Western Europe from 19% to 16%, and in North America, from 21% to 16%. In Eastern Europe, the error rate decreased from 49% to 33% in 1991, whereas the rate remained high in South America at 60% in 1988 and 72% in 1991. The high error rates in South America and Eastern Europe reflected a lack of good quality serological typing reagents. The 16% typing errors in Western Europe and North America demonstrated the current limit of serological techniques for cadaver donor typing and underlined the need for prospective DNA typing.

DNA↗
PubMed1994

HLA class II DNA-RFLP typing in 102 individuals from Northern Greece.

The serological identification of HLA class II alleles is often doubtful. Since accurate HLA typing is essential for the matching of donor-recipient pairs in allogeneic transplantation, an effort was made to establish DNA restriction fragment length polymorphism (RFLP) typing and to assess the correlation between the serological and RFLP techniques in the population of Northern Greece. One hundred and two healthy individuals (204 HLA-DR alleles) from Northern Greece were HLA-DR, DQ typed with both the microcytotoxicity and the Taq I RFLP method, using three exon-specific probes. DNA-RFLP typing revealed (1) concordant results with serology in 69.9% (142/204) of the alleles and (2) at least one HLA-DR allele discrepant to serology in 30.4% (62/204) of the alleles. Incorrect serological DR types (weak reactions or inability to distinguish between two alleles with a common epitope) were identified in 54 alleles (26.5%), while 3.9% (8/204) of serological "blank" alleles turned out to be definable alleles by RFPL. Of the individuals tested, 10.8% (11/102) were DR-homozygous by RFLP. This comparison of results obtained by serology and RFLP demonstrated the necessity of the clinical application of DNA typing, especially for organ transplantation where accurate HLA typing has an important influence on graft survival.

Alleles↗
PubMed1994

Prolonged rat allograft survival induced by temporary elimination of alpha/beta T cells with monoclonal antibody.

We tested the ability of lewis (LEW; RT-1(1)) recipients to reject DA (RT-1av1) cardiac allografts following the selective elimination of alpha/beta T cells with the mouse monoclonal antibody R73. One group of adult rats (6 weeks old) received 1000 microg R73 i.p. on days 2 and 1 before transplantation, and 100 microg R73 every third day after transplantation up to day 18. Prolonged cardiac graft survival was noted (30, 30, 32, 51, 62, 108, > 500, > 500, > 500 days). Untreated controls (n = 10) rejected their grafts within 7 +/- 1 days. R73 therapy induced a dramatic decrease in alpha/beta T cells from 69% before treatment to 5% within the first 5 days, followed by an increase to 64% by day 8. The T cell increase was paralleled by the appearance of anti-mouse antibody. A second group of adult rats (10 weeks old) received the same treatment. These "older" recipients rejected their grafts within 20 +/- 5 days. Chronic R73 therapy from birth until the day of transplantation (100 microg R73 i.p. twice a week) resulted in graft survival of 37 +/- 9 days in eight animals. Two rats had a graft survival of more than 200 days. When chronic R73 therapy was continued to day 70 after transplantation, DA hearts were accepted well in all animals for more than 100 days. Alpha/beta T cells were virtually absent throughout the whole time of treatment. Antibodies against R73 were not detected. We concluded that selective elimination of alpha/beta T cells has a strong effect on allograft survival.

Age Factors↗
PubMed1994

Heart allograft survival in rats following immunization with soluble peptide MHC class I donor antigens: evidence for the role of indirect recognition in rejection.

The current series of experiments addressed the question of whether indirect priming with donor MHC antigens affects heart allograft survival. LEW (RT-1(1)) rats were immunized with a mixture of two peptides corresponding to the variable region of MHC class I locus Aa antigen (alpha1 and alpha2 domain). The recipients were transplanted with a DA (RT1-1a) heart 1 month after immunization, and graft survival was closely monitored by ECG. All peptide-treated recipients presented with anti-peptide antibodies at the time of transplantation and developed a strongly accelerated graft rejection. These findings indicated that indirect recognition of MHC I donor antigens promotes heart allograft rejection.

Amino Acid Sequence↗
PubMed1994

Pretransplant serum IgA concentration and IgA-anti-Fab autoantibody activity as prognostic indicators of kidney graft survival.

IgA concentration and IgA-anti-Fab autoantibody activity were tested in pretransplant sera of 308 kidney graft recipients. Recipients with a serum IgA concentration of 2 g/l or greater had a 1-year graft survival rate of 83%, compared with a 68% rate in recipients with serum IgA of less than 2 g/l (P < 0.005). Serum IgA concentration and IgA-anti-Fab autoantibody activity were significantly associated (r = 0.38, P < 0.0001). Recipients with a high pretransplant IgA-anti-Fab activity had a significantly better graft survival rate (81%) than patients with low pretransplant IgA-anti-Fab (67%, P < 0.025). When IgA-anti-Fab and serum IgA were considered together, 137 recipients with high IgA-anti-Fab and high serum IgA had a 86% 1-year graft survival rate, which was significantly better than the 63% survival rate in patients with low IgA-anti-Fab and low serum IgA (P < 0.0005). The pretransplant serum IgA level and IgA-anti-Fab autoantibody activity were excellent predictors of kidney graft outcome.

Autoantibodies↗