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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 181 records · Page 10Linked to original sources
PubMed1993

Computer analysis of cadaver kidney allocation procedures.

Data of 32,000 donors were utilized for a computer simulation to analyze the effect of selection parameters on the outcome of kidney transplants. If the HLA match grade is considered for organ allocation, the overall 1-year graft survival rate is up to 7% higher for first cadaver transplants and up to 12% higher for second transplants than if HLA matching is disregarded. This solely success-oriented organ allocation method, however, leads to prolonged waiting times for patients with rare HLA phenotypes. We developed a selection procedure that yields results near the theoretical optimum: 95% of all patients can be transplanted with 0-2 HLA-A, -B, -DR antigen mismatches, the average waiting time decreases to 20 months, and no patient needs to wait longer for a transplant than 6 years. The overall graft survival rate is only 0.4% lower than the rate obtainable with strictly HLA-oriented allocation. The method prevents "poorly matchable" patients from accumulating on the waiting list. Additionally, the unfavorable race ratio in the North American recipient pool can be largely normalized.

Cadaver↗
PubMed1992

Striking inverse association of IgG-anti-Fab gamma antibodies and CD4 cell counts in patients with acquired immunodeficiency syndrome (AIDS)/AIDS-related complex.

The contribution of autoimmune phenomena to the pathogenesis of acquired immunodeficiency syndrome (AIDS) is poorly understood. We investigated the relationship between IgG-anti-Fab gamma autoantibodies and the main immunologic feature of AIDS, the decrease of CD4+ helper lymphocytes. Sera of 33 human immunodeficiency virus (HIV) infected (HIV+) hemophilia patients with AIDS/AIDS-related complex (ARC), 57 HIV+ patients without AIDS/ARC, 23 HIV-negative (HIV-) patients, and 76 healthy controls were tested for antibody activity against the Fab region of IgG. Patients with AIDS/ARC had significantly higher IgG-anti-Fab gamma activity than HIV+ patients without AIDS/ARC, HIV- patients, or controls (P less than .0001). A striking inverse association was found between IgG-anti-Fab gamma and CD4+ cell counts (r = -.69; P less than 10(-6)). Sequential testing in 16 AIDS/ARC patients showed that an increase in the IgG-anti-Fab gamma activity was invariably accompanied by a decrease in the CD4+ cell count. IgG-anti-Fab gamma antibodies may play an important role in the immunopathogenesis of AIDS.

AIDS-Related Complex↗
PubMed1992

An immunoglobulin-specific autoantibody occurring during alloimmunization suppresses the antibody response.

Our previous studies showed that a broadly reactive immunoglobulin G (IgG) anti-immunoglobulin (IgG-anti-Ig) autoantibody is induced during the immune response of LEW rats to BN blood cells. The present experiments analyze the immunoregulatory effect of this physiological autoantibody on antigen receptor-activated B cells in cell cultures. The results show that: (a) At 0.9 pg IgG-anti-Ig/10(6) B cells, an almost complete suppression of the antibody response is induced: we calculated that a few IgG-anti-Ig molecules are sufficient to suppress the antibody response of one B cell; (b) IgG-anti-Ig-induced B-cell suppression is dose-dependent; (c) IgG-anti-Ig suppresses B cells contained in their natural environment (mixed spleen cell population). These data demonstrate that the IgG-anti-Ig autoantibody is an extremely efficient regulatory molecule of the alloimmune response.

Animals↗
PubMed1992

DNA typing: an important step forward? Collaborative Transplant Study.

In a collaborative project which was supported by 96 transplant centers, DNA typing of HLA-DR antigens was carried out on over 7,000 transplant donors and recipients at 8 participating laboratories. Approximately 25% of the individuals were found to have been typed incorrectly by serological means. An analysis of over 2,500 first cadaver kidney transplants showed a significant correlation of matching for the HLA-DR antigens in transplants where the serological typing was confirmed by DNA typing. In transplants where the serological typing was found to be incorrect, the analysis of serological HLA-DR mismatches resulted in no correlation with graft outcome whereas a significant correlation was found when the corrected DNA typed HLA-DR antigens were analyzed. Transplants which had been reported to the Collaborative Transplant Study based on serological typing as matched for HLA-A, -B, -DR or HLA-B, -DR were found to have a superior graft survival rate only if HLA-DR compatibility was confirmed by DNA typing.

DNA Fingerprinting↗
PubMed1992

Success rate and impact of HLA matching on kidney graft survival in highly immunized recipients. Collaborative Transplant Study.

From 1985 to 1990, 225 highly immunized recipients were transplanted based on a program of serum exchange and priority allocation of kidneys to crossmatch negative recipients. The 1-year graft survival rate in first transplant recipients was 73% and in second transplant recipients, 71%. Recipients of third or fourth transplants had a 25% lower success rate. HLA matching exerted a significant influence on graft outcome. Twenty-five first or second grafts with zero mismatches for HLA-B,-DR had a 91% 1-year survival rate, in contrast to a 58% survival rate of 38 grafts with of three or four HLA-B,-DR mismatches (log rank P < 0.001).

Graft Survival↗
PubMed1992

Strength of HLA-A, HLA-B, and HLA-DR mismatches in relation to short- and long-term kidney graft survival. Collaborative Transplant Study.

The separate influence of HLA-A, HLA-B, and HLA-DR mismatches on short- and long-term kidney graft survival was analyzed in a series of over 40,000 recipients of first cadaver kidney transplants. As expected, during the early posttransplant period, HLA-DR mismatches had a stronger influence on graft survival than HLA-B mismatches, and HLA-A mismatches had a very small influence. Surprisingly, during the period from 6 months to 5 years post transplantation, all three HLA loci had approximately the same influence. When the graft survival computation was started at 100% at 6 months, the difference between grafts with zero or two mismatches at the end of 5 years was 6%, regardless of whether HLA-A, HLA-B, or HLA-DR antigens were analyzed. The influence of the three loci was additive so that the survival rate difference between transplants with zero or six mismatches for HLA-A, -B, -DR was 17% at 5 years. We concluded that, although the HLA-A locus exerts only a weak influence during the early posttransplant course, its influence on long-term survival is comparable to that of HLA-B and HLA-DR. In order to obtain optimal long-term survival, all three loci must be considered in the donor-recipient matching procedure.

Cadaver↗
PubMed1992

Current status of HLA matching in renal transplantation. The Collaborative Transplant Study.

The impact of HLA compatibility on the success rate of kidney transplants was studied in over 80,000 recipients of primary transplants. The transplants were done from 1982 to 1991 at over 300 transplant centers in 43 countries. The results show that matching the HLA chromosomes in related donor transplants has a striking influence. It is also important that matching for individual HLA antigens in cadaver transplants provides a highly significant improvement in graft survival (P less than 0.0001). After 5 years, matched grafts have a survival rate approximately 20% higher than completely mismatched grafts. The matching effect is particularly strong in presensitized and second graft recipients. There is now direct evidence that even if it is necessary to transport well-matched kidneys a long way, they have a significantly higher success rate than locally transplanted poorly matched kidneys. New data based on molecular technology show that the precise identification of HLA-DR antigens by DNA typing further improves the success rate of HLA-matched transplants.

Follow-Up Studies↗
PubMed1992

Restriction mechanisms of B cell regulation by a physiological IgG-anti-immunoglobulin autoantibody.

Immunization of LEW rats with strongly histoincompatible BN blood cells induces, in addition to anti-donor antibody, a broadly reactive IgG autoantibody which binds to IgG and IgM molecules (IgG anti-Ig). Minute amounts of affinity purified IgG anti-Ig (0.2 pg/10(6) cells) suppress the antibody production in vitro of antigen receptor (AgR)-stimulated B cells derived from rats of the same strain. The suppressive antibody is also active in the whole serum IgG fraction. Importantly, anti-Ig-induced suppression is governed by restriction mechanisms: only AgR-occupied B cells are affected, the suppression is cell cycle dependent, and maximum suppression is obtained at an optimum IgG concentration. Treatment of rats in vivo with 0.8 mg Ig-anti-Ig (whole IgG fraction) along with allogeneic cells resulted in nearly complete suppression of the anti-donor antibody response. Possible mechanisms of B cell suppression by IgG anti-Ig are crosslinking of AgR with FcR, or cocapping of the two receptors with sterical interaction as a consequence of their separate occupation. Both alternatives lead to the release of an inactivating signal.

Animals↗
PubMed1992

Regulation of antibody response by an IgG-anti-Ig autoantibody occurring during alloimmunization. I. A few IgG molecules inactivate one B cell.

We have shown previously that alloimmunized rats develop a broadly reactive IgG-antiimmunoglobulin autoantibody in addition to antidonor antibodies. The findings presented herein demonstrate that this "physiological" antibody suppresses antigen receptor-induced IgM production of B cells derived from rats of the same strain. When affinity-purified IgG-anti-Ig was added to cell cultures, the antibody production of B cells was maximally inhibited at the minute concentration of 0.9 pg/10(6) cells. Higher or lower IgG-anti-Ig concentrations resulted in weaker suppression. The same result was obtained when spleen lymphocytes were used instead of purified B cells. Based on the molecular weight of IgG and Avogadro's number, our results indicate that a few molecules of IgG-anti-Ig are sufficient to inhibit the antibody production of a single B cell. Activity at this minuscule concentration demonstrates that IgG-anti-Ig antibodies are exquisitely active immunoregulatory molecules. In addition to the stimulatory effect of IgM-anti-Ig rheumatoid factors reported by others, our findings define the second component of an immunoregulatory mechanism: suppression of the B cell response by an IgG-anti-Ig autoantibody produced during alloimmunization.

Animals↗
PubMed1992

Regulation of antibody response by an IgG-anti-Ig autoantibody occurring during alloimmunization. II. Selective inactivation of antigen receptor-occupied B cells.

Heterologous antiimmunoglobulin antibodies are efficient regulators of the B cell response. We have shown that during the immune response against allogeneic cells the immune system develops autologous IgG-antiimmunoglobulin. A few molecules of this "physiological" autoantibody suppress the IgM production of one B cell in vitro. In the current series of experiments we further define the regulation of antigen receptor-activated B cells by this autoantibody. To mimic the in vivo situation, where IgG-anti-Ig appears a few days after alloimmunization, the antibody's effect on an already ongoing B cell response was studied. Interestingly, we found that the IgG-anti-Ig loses its suppressive effect when added to the cell culture 1 or 2 days after B cell activation, but that suppression can be completely restored when the cells are restimulated via their antigen receptor. Thus, the IgG-anti-Ig antibody suppresses B cells only when their antigen receptor is occupied. Even restimulated B cells become refractory 8 hr after activation, and later (24 hr) regain their susceptibility to IgG-anti-Ig-induced suppression. The Fc receptor is involved in mediating suppression since the antibody's suppressive capacity is abolished after removal of its Fc region. Possible mechanisms of B cell suppression by IgG-anti-Ig are crosslinking of antigen receptor with Fc receptor, or cocapping and functional interaction of the two receptors as a result of their separate occupancy. Our experiments demonstrate that B cell regulation by IgG-anti-Ig produced during an immune response to allogeneic cells is governed by 3 restriction mechanisms: antigen receptor occupancy, activation stage dependency, and optimal antibody concentration.

Animals↗
PubMed1992

The association of kidney graft outcome with pretransplant serum IgG-anti-F(ab')2 gamma activity.

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).

Antibodies, Anti-Idiotypic↗
PubMed1992

Soluble IL-2 receptor and tumour necrosis factor-alpha in plasma of haemophilia patients infected with HIV.

We measured plasma concentrations of soluble receptors for IL-2 (sIL-2R) and tumour necrosis factor-alpha (TNF-alpha) in 149 haemophilia patients. Soluble IL-2R levels were elevated in 37% of 62 HIV-seronegative patients (mean 570 +/- 27 U/ml versus 361 +/- 17 U/ml in the control group, P less than 0.0001), in 78% of 68 HIV-seropositive patients (928 +/- 49 U/ml, P less than 0.0001), and in 95% of 19 AIDS/ARC patients (1578 +/- 199 U/ml, P less than 0.0001 compared with controls and with HIV-seronegative patients; P less than 0.005 compared with HIV-seropositive asymptomatic patients). A negative correlation was observed between sIL-2R, relative and absolute numbers of CD4+ cells (P less than 0.0001), and CD4/CD8 ratios (P less than 0.0001). There was also a negative correlation between sIL-2R in plasma and the cellular expression of IL-2R (P less than 0.001). We found a significant association of sIL-2R and plasma neopterin (P less than 0.0001). With progression of the disease from HIV-seronegative to seropositive without symptoms and to full manifestation of AIDS/ARC, sIL-2R plasma levels increased. The highest levels were found at the time of diagnosis of AIDS/ARC, but the levels decreased again during the following 18 months. Eight per cent of HIV-seronegative patients, 32% of HIV-seropositive patients, and 24% of patients with AIDS/ARC had increased plasma TNF-alpha. We conclude that sIL-2R and TNF-alpha plasma levels are elevated in HIV-infected haemophilia patients and that sIL-2R is a marker for disease progression from asymptomatic HIV-seropositive to AIDS/ARC.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Autoantibodies in HIV-infected hemophilia patients against different epitopes on CD4+ lymphocytes and recombinant CD4.

We studied 684 sera obtained from 20 hemophilia patients with AIDS/AIDS-related complex (ARC), 89 asymptomatic HIV+, 76 HIV- hemophilia patients and 151 healthy controls for antibodies against recombinant CD4 (rCD4). Twenty-two percent of AIDS/ARC patients, 10% of asymptomatic HIV+ patients, 17% of HIV-patients, and 1% of healthy controls had anti-rCD4 antibodies. Purified anti-rCD4 antibodies did not react with human CD4+ lymphocytes. This may explain why formation of anti-rCD4 antibodies correlated neither with the occurrence of autoantibodies against CD4+ lymphocytes nor with a decrease in CD4+ cell counts. Antibodies that were eluted from CD4+ lymphocytes after sequential adsorption and elution with separated CD8+ and CD4+ cells reacted with CD4+ lymphocytes of only some healthy individuals, suggesting diversity of CD4 expression.

Acquired Immunodeficiency Syndrome↗