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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 109 records · Page 6Linked to original sources
PubMed1996

Identification of complement activation sites in human immunodeficiency virus type-1 glycoprotein gp120.

Recombinant glycoprotein 120 (rgp120) of human immunodeficiency virus type-1 (HIV-1) activates the human complement system in the absence of anti-gp120 antibodies. HIV-1 glycoprotein gp120 can dissociate from the viral envelope either spontaneously or after binding of HIV-1 to the CD4 molecule. As a consequence, gp120 can circulate in the patient's serum and attach to the surface of uninfected CD4+ T cells. Complement activation by cell-bound HIV-1 glycoprotein gp120 with subsequent opsonization may represent a mechanism for the elimination of uninfected CD4+ cells by the reticuloendothelial system, thereby enhancing the progression of HIV disease. In the current study, the complement proteins C4,C3,C5,C9, and properdin were found to bind to a synthetic peptide covering positions 233-251 of the gp120BRU sequence on incubation with normal human serum. Complement activation by the peptide was comparable with that induced by aggregated IgG, complete rgp120, and the previously described complement-activating gp41-peptide 609-623. Activation occurred via the classical pathway and was abrogated in the presence of EDTA, Mg2+/EGTA, or C4-deficient human serum. Peptides partly overlapping the sequence 233-251 activated complement to a lesser extent. The complement-activating capacity of the gp120 sequence 233-251 was not restricted to the HIV-1BRU isolate, because a peptide from the corresponding sequence of the HIV-1MN strain was also capable of activating complement. An additional strong complement-activating site was identified in the gp120 sequence 321-360 of the HIV-1MN strain. These data indicate that distinct sites in gp120 are able to activate human serum complement via the classical pathway in the absence of anti-gp120 and independent of glycosylation.

Amino Acid Sequence↗
PubMed1996

Evaluation of the permissible mismatch concept.

Maruya et al. described a method of separating one HLA-A+B+DR mismatched transplants into permissible and immunogenic categories (published in Clinical Transplants 1993). For the permissible subgroup, they observed an outcome similar to that of zero-A+B+DR mismatched transplants. The classification was based on the HLA type combination of donor and recipient. We evaluated this concept with the data of the Collaborative Transplant Study (CTS). We did not obtain significant differences between the outcome of immunogenic and permissible mismatched transplants. The pairwise p-values for the comparison of zero-mismatched with permissible mismatched transplants are significant for cadaver transplants. The indifferent results obtained in our analysis do not support the concept of permissible mismatches. A more restrictive definition of the permissible mismatches might be helpful. The current method appears to be of insufficient reliability due to the relatively small numbers of transplants in the individual subgroups used to identify permissible combinations.

Cadaver↗
PubMed1996

Five-year results of renal transplantation in highly sensitized recipients. Collaborative Transplant Study.

A special program for the priority allocation of cadaver donor kidneys to highly sensitized patients was initiated 10 years ago. During the period from 1985 to 1994, 329 transplants were performed at 35 transplant centers. Five-year graft survival rates were: 59 +/- 4% for 156 first grafts, 52 +/- 5% for 133 second grafts, and 18 +/- 7% for 40 third or fourth grafts. The success rates of first and second grafts were comparable with the corresponding success rates of first and second cadaver transplants in non-sensitized recipients reported to the Collaborative Transplant Study. There was a highly significant impact of HLA matching on graft survival. Among first and second grafts, 35 transplants with no mismatches for HLA-B+DR had a 76 +/- 8% success rate at 5 years, compared with a 55 +/- 4% rate for 208 grafts with one or two mismatches and a 37 +/- 8% rate for 46 grafts with three or four mismatches (weighted regression P < 0.001).

Graft Survival↗
PubMed1996

Allograft survival following immunization with membrane-bound or soluble peptide MHC class I donor antigens: factors relevant for the induction of rejection by indirect recognition.

T cells recognize foreign antigens in the form of peptide fragments resulting from antigen processing by antigen-presenting cells. In contrast to this indirect recognition, MHC molecules of foreign cells can be directly recognized by T cells. Direct recognition has for a long time been considered the only mechanism responsible for transplant rejection. Recent studies have provided evidence of a role of indirect recognition in rejection. In the current series of experiments, we studied the influence of indirect alloactivation, induced either by donor MHC class I peptides or by membrane-bound MHC I molecules, on heart allograft rejection in rats. Recipients were immunized before transplantation with synthetic donor MHC I peptides. The animals developed antibody and T-cell responses. Depending on the rat strain, peptide pretreatment either had no effect on graft survival (DA-->PVG; untreated controls 8.5 +/- 0.6 days, treated rats 9.5 +/- 0.6 days) or led to accelerated rejection (DA-->LEW; untreated controls 7.5 +/- 0.3 days, treated rats 5.1 +/- 0.2 days; P < 0.0002). Importantly, sensitization by indirect activation induced acute rejection in a donor-recipient combination (LEW.1A-->LEW.1WR2) in which neither direct nor indirect recognition led to rejection (untreated controls > 400 days, pretreated rats 15 +/- 4.2 days). Another group of animals was immunized with allogeneic or congenic erythrocytes carrying the MHC I antigen from which the peptides were derived. Although the immunization elicited a measurable immune response, it did not lead to accelerated rejection. We conclude that sensitization by indirect recognition is able to initiate an acute rejection even in recipients in which neither direct nor indirect recognition is effective, and that this effect is strain-dependent. The form in which the donor antigen is administered is decisive for the induction of rejection by indirect activation.

Animals↗
PubMed1996

A single center evaluation of the Collaborative Transplant Study (CTS) DNA project.

Historical HLA class II serological typing results of transplantations performed in "The Leuven Collaborative Group for Transplantation" were subjected to retrospective Restriction Fragment Length Polymorfism (RFLP) DNA control typing by the Collaborative Transplant Study (CTS) DNA project using Polymerase Chain Reaction (PCR)-based DNA methods. We re-evaluated the serology/ RFLP-discrepant CTS DNA data for our local patients transplanted during a historical period (January 1988 until May 1992) before any class II DNA typing was performed in our tissue typing laboratory. These retyping results confirm both the CTS data for patient typing and the Eurotransplant data for donor typing. A confirmed high discrepancy rate of 19.0% (after exclusion of 2.2% transcription errors) was found in the patient population. A low discrepancy rate of 6.8% (after exclusion of 2.2% transcription errors) for the donor population is concordant with the Eurotransplant donor data. Only 4 of the 588 individuals were found to be incorrectly typed by the RFLP method; all involving the specificities DRB1*1102. This indicates that RFLP typing, as performed by the CTS DNA project, can be considered a valid, retrospective DNA typing system for the accurate interpretation of class II matching in organ transplantation. A second conclusion to be drawn from this study is the need for prospective DNA typing for kidney transplant recipients, as the discrepancy rate in this cohort is high. Our results suggest that with good quality serological HLA-DR typing, prospective donor DNA typing is not urgently needed.

Belgium↗
PubMed1996

Does AIDS emerge from a disequilibrium between two complementary groups of molecules that mimic MHC?

There is increasing evidence that a disturbance of self-nonself-recognition plays an important role in the immunopathogenesis of AIDS. Here, Caner Susal, Volker Daniel and Gerhard Opelz speculate that the immune system is balanced between two groups of molecules that mimic major histocompatibility complex (MHC) proteins; AIDS is suggested to emerge as a consequence of human immunodeficiency virus (HIV) disturbing this balance in favor of anti-MHC class II responses.

Acquired Immunodeficiency Syndrome↗
PubMed1996

Association of T cell dysfunction with the presence of IgG autoantibodies on CD4+ lymphocytes in haemophilia patients; results of a 10-year study.

HIV induces progressive dysfunction followed by numerical depletion of CD4+ lymphocytes. IgG autoantibodies and gp 120-containing immune complexes have been implicated in the pathogenesis of AIDS. We carried out a longitudinal study in 19 HIV- and 72 HIV+ haemophilia patients over a 10-year period in order to investigate a possible relationship between the occurrence of autoantibodies and CD4+ lymphocyte changes. IgM, IgG, C3d and gp120 on the surface of CD4+ lymphocytes were determined in heparinized whole blood with flow cytometry and double-fluorescence. The in vitro response of autoantibody-coated cells was tested in cell cultures with concanavalin A (Con A), phytohaemagglutinin (PHA), pokeweed mitogen (PWM) anti-CD3 MoAb or pooled allogeneic stimulator cells (MLC). After a 10-year follow up, 12 of 71 HIV+ and 16 of 19 HIV- haemophilia patients showed no evidence of immunoglobulins on circulating CD4+ lymphocytes. HIV- haemophilia patients without autoantibodies had CD4+ and CD8+ cell counts in the normal range (957+/-642/microliters and 636+/-405/microliters) and normal T cell responses in vitro (mean relative response (RR) > or = 0.7). In contrast, HIV+ haemophilia patients showed immunological abnormalities which were associated with the autoantibody and immune complex load of CD4+ blood lymphocytes. HIV+ patients without autoantibodies had a mean CD4+ lymphocyte count of 372+/-274/microliter, a mean CD8+ lymphocyte count of 737+/-435 microliter, and normal T lymphocyte stimulation in vitro (mean RR > or = 0.7). HIV+ patients with complement-fixing IgM on CD4+ lymphocytes had somewhat lower CD4+ (255+/-246/microliters, P = NS) and CD8+ (706 +/- 468/microliters, P = NS) lymphocyte numbers, and also normal T lymphocyte stimulation (mean RR > or = 0.7) in vitro. However, patients with complement-fixing IgG autoantibodies showed a strong decrease of CD4+ (150 +/- 146/microliters, P< 0.02) and CD8+ (360 +/- 300 microliters, (P<0.02) lymphocytes and impaired CD4+ lymphocyte stimulation in vitro with a mean RR of 0.5+/-0.5 for Con A (P = NS), 0.7 +/- 0.8 for PHA (P<0.03), 0.4 +/- 0.4 for PWM (P = NS), 0.8 +/- 1.2 for anti-CD3 MoAb (P<0.04) and 0.7 +/- 1.0 for pooled allogeneic stimulator cells (P=0.05). Patients with gp120-containing immune complexes on CD4+ blood lymphocytes demonstrated strongly decreased CD4+ (25+/-35/microliters, P<0.0001) and CD8+ (213+/-212/microliters, P<0.006) lymphocyte counts as well as strongly impaired T lymphocyte responses in vitro upon stimulation with PHA (RR 0.2+/-0.1, P<0.02), PWM (RR 0.2+/_0.2, P=0.05), anti-CD3 MoAb(RR 0.1+/-0.1, P<0.04), and allogeneic stimulator cells (RR 0.2+/-0.1, P<0.02). These data led us to speculate that autoantibody formation against CD4+ lymphocytes is an important mechanism in the pathogenesis of AIDS. We hypothesize that autoantibodies against circulating CD4+ lymphocytes inhibit CD4+ cell function, especially the release of cytokines, and induce CD4+ cell depletion. The reduction and dysfunction of CD4+ lymphocytes may be responsible for the CD8+ cell depletion observed in HIV+ patients.

Antigen-Antibody Complex↗
PubMed1996

[Illness stage and IgA-anti-Fab/F(ab')2 autoantibody activity in serum of patients with malignant head-neck tumors].

BACKGROUND: Patients with malignant tumors of the head and neck often show immune defects. Increased serum IgA levels have been reported in these groups of patients. We investigated whether IgA-anti-Fab or IgA-anti-F(ab')2 autoantibodies, which have been shown to correlate with severe dysfunction of the immune system, also appear in patients with head and neck cancer. PATIENTS: Sera of 110 patients with squamous cell carcinoma, eight patients with adenoid cystic carcinoma, and 57 healthy controls were tested with an ELISA for IgA-anti-Fab autoantibody activity. RESULTS: Patients with head and neck cancer showed a higher IgA-anti-Fab activity (OD:399, n = 118) than healthy controls (OD: 84, n = 57, p < 0.0001). An association between stage of disease and IgA-anti-Fab activity could be established in patients with SCCHN. Stage IV patients had a significantly higher IgA-anti-Fab activity (OD: 538, n = 51) than stage 1 patients (OD: 283, n = 18, p < 0.05). Patients with stage II (OD: 293, n = 13) or stage III (OD: 379, n = 28) showed intermediate activity. Also a higher IgA-anti-Fab activity than in healthy controls was demonstrated in the eight patients with ACCHN (OD: 314, n = 8, p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within six months after testing (OD: 1004, n = 8). Similar results were obtained for IgA-anti-F(ab')2 autoantibodies. Our findings suggest an association between autoimmunity and final desintegration of physiological body functions. CONCLUSIONS: The occurrence of IgA-anti-Fab/IgA-anti-F(ab')2 autoantibodies might be interpreted as an aspect of immune deficiency in patients with malignant tumors of the head and neck.

Adult↗
PubMed1996

CD8+ lymphocyte decrease in HIV disease: association with anti-CD4+ but not with anti-CD8+ lymphocyte autoantibodies.

HIV+ patients form autoantibodies against CD4+ and CD8+ lymphocytes. It was shown that anti-CD4+ lymphocyte autoantibodies are associated with the depletion of CD4+ cells. In the present study we analyzed the relationship of anti-CD4+ and anti-CD8+ autoantibodies with the CD8+ lymphocyte decrease commonly observed during HIV disease. IgM and IgG antibodies as well as complement fragments were determined on the surface of CD4+ and CD8+ lymphocytes using double fluorescence flow cytometry. Anti-CD8+ lymphocyte autoantibodies were found more often in HIV + hemophilia patients (75/105 = 71%) than HIV- hemophilia patients (13/37 = 35%; p < 0.0001), patients with pharyngeal carcinoma (20/44 = 45%; P = 0.002), habitual abortions (3/13 = 23%; p = 0.0009) or healthy individuals (93-223 = 42%; p < 0.0001). Anti-CD8+ antibodies, mostly of the IgM type, occurred significantly more frequently than anti-CD4+ antibodies in healthy controls (p < 0.0001), patients with pharyngeal carcinoma (p = 0.0001), or HIV- patients (p = 0.01). In HIV+ patients, however, anti-CD4+ autoantibodies were found more often than anti-CD8+ antibodies (85 vs 71%; p = 0.02). 70 of 104 (67%) HIV+ patients had autoantibodies on both CD4+ and CD8+ lymphocytes and the IgG/IgM/C3d autoantibody pattern was identical in 31 (44%) of the patients. Interestingly, peripheral blood CD8+ cell counts were significantly associated with anti-CD4+ (p = 0.01) but not with anti-CD8+ lymphocyte autoantibodies. It is hypothesized that the inhibition and depletion of CD4+ cells by anti-CD4+ autoantibodies is associated with a loss of regulatory functions that leads to a depletion of antiviral cytotoxic CD8+ lymphocytes.

Autoantibodies↗