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Biomedical subjects

G Opelz

Publications and source records attributed to G Opelz.

At least 289 records · Page 16Linked to original sources

Importance of preoperative (not peroperative) transfusions for cadaver kidney transplants.

The outcome of 684 cadaver kidney transplants in recipients who had never been transfused was compared to that in 371 recipients who had been transfused only preoperatively. No significant difference in graft survival was observed. Peroperative transfusions were ineffective regardless of their number or the type of blood product. These results contradict a recent report on the benefits of peroperative transfusions. Transfusions given before transplantation continued to show a striking graft improvement effect in a new series of 538 transplants performed in 1979.

Blood Group Antigens↗

Lymphocytotoxic antibody responses to transfusions in potential kidney transplant recipients.

A series of 737 hemodialysis patients were studied for the relationship between lymphocytotoxic antibody formation and blood transfusions; 331 thereof were studied prospectively. With up to 20 transfusions, highly reactive (greater than 90% reactivity against random panel) antibodies were not found in any of the prospectively studied males or females without previous pregnancies. Nearly 90% of the males failed to form antibodies against greater than 10% of the panel donors. Patients with previous pregnancies developed antibodies at a much higher rate. Among 316 patients tested, antibodies against B cells were found more frequently than antibodies against T cells. Both T and B cell antibody levels often decreased in spite of additional transfusions. It is concluded that the risk of rendering a patient untransplantable because of sensitization as a result of transfusions is very small.

Antibody Formation↗

An alternative to cadaver kidney transplants for patients with insulin-dependent diabetes mellitus.

The benefits of successful kidney transplants for patients with end stage renal disease associated with insulin-dependent diabetes mellitus are well known, and the potential advantages of earlier transplantation have been emphasized in other reports. Cadaver transplants, which are not always available for these patients, have not provided a high degree of success in many centers. This has discouraged the use of transplants unless well matched related donors are available. Most patients do not have well matched family members who are able to donate. We have attempted to increase the availability of related transplants for diabetic patients by using a new protocol in which related donors who are poorly matched by mixed lymphocyte culture (MLC) testing (stimulation index (SI) greater than or equal to 7) can often serve as the source of the transplant. This protocol of pretransplant donor-specific transfusions (DSTs) has been applied to 20 diabetic patients. Sixteen transplants have been performed after serial immunological studies following the DSTs detected no specific evidence of recipient sensitization to the respective transfusion donors. Only one of the transplants has been rejected, and this occurred in a patient who intentionally terminated immunosuppressive therapy. Graft survival for the group of 16 patients is 93 and 84% at 1 and 3 years, respectively. The quality of renal function for most of the patients is very good, with a mean serum creatinine of 1.9 and 1.5 ml/dl for those transplants at risk for 12 and 24 months. This new method has given encouraging results for poorly matched related transplants in diabetic patients and makes earlier transplantation possible by providing an alternative to cadaver transplants.

Adult↗

The association of an HLA 'asthma-associated' haplotype and immediate hypersensitivity in familial asthma.

Fifty-seven members from ten families in which one parent and at least one child have asthma were studied with dilutional skin tests and RAST to grass pollens after determination of HLA haplotypes. We found no direct evidence for linkage of a hypothetical asthma locus with HLA or for a significant association of asthma with HLA haplotypes. Linkage between the HLA loci and a gene or genes which allow for the expression of clinical asthma could neither be proven nor disproven due to the small sample size. All of the asthmatic children had positive dilutional skin tests and RAST, suggesting that atopic asthma may be genetically controlled by the HLA chromosome (chromosome 6). Nonetheless, determination of the histocompatibility antigens can increase the value of predictive risk analysis for asthma. Such a determination may be important in the early identification of a child born to a family with atopic asthma.

Adult↗

Pretreatment with donor-specific blood transfusions in related recipients with high MLC.

Pretreatment with deliberate DST has not resulted in hyperacute or irreversible rejection in patients receiving kidneys after negative donor-specific crossmatches, but has afforded immunologically disparate related recipients enhanced opportunity at successful transplantation. Additionally, with a post-transplant course paralleling that of HLA-identical siblings, high-dose immunosuppressive therapy for rejection has been spared in many recipients. Transplantation, however, proved unsuccessful in a patient receiving a kidney from his positive B-warm crossmatch blood donor in a protocol departure. This case experience and subsequent antibody studies have reconfirmed our initially established criterion of not proceeding with transplantation against a persistently positive B-warm donor-specific crossmatch. By pursuing the initially established DST protocol, it appears that a potentially unsuccessful living related transplant can be avoided, while the transplants actually performed have enhanced prospects of success. The nature of the various immunologic responses in this patient population remain to be more clearly defined.

Antibody Formation↗

Blood transfusions as "transplantation pretreatment": incidence of immunization against unfractionated lymphocytes, T- and B-lymphocytes.

Since May 1980 patients waiting for cadaveric kidney grafts have been pretreated with at least 5 units of leukocyte poor blood. In this study we have analysed the occurrence of antibodies against unfractionated cells, T and B cells following these transfusions. Of the previously untransfused nineteen patients none formed cytotoxic T cell antibodies while warm B cell antibodies were found in sera from three patients, one being broadly cytotoxic killing also unfractionated lymphocytes. Broadreactive cold B cell antibodies were found in serum from one patient. Of the previously transfused fourteen patients none formed T cell antibodies following transfusions with the "lacking" blood units, while two patients formed warm B cell antibodies. Thus, immunization against B cells was more common than immunization against T cells. The significance of these B cell antibodies is unclear, but these antibodies did not show anti-HLA-DR specificity.

Adult↗

Graft survival with high levels of cytotoxic antibodies.

In this study, pretransplant transfusions significantly improved the survival of first cadaver kidney transplants. Large numbers of transfusions had the same influence on graft survival as small number of transfusions. Graft survival was not influenced by pretransplant antibody levels, and the beneficial effect of transfusions was also independent of highest pretransplant antibody levels. The positive relationship between transfusions and cytotoxic antibodies was shown to be highly significant. B-warm and T-warm antibodies were both increased by transfusions and tended to occur together. B-cold antibodies occurred independent of transfusions, B-warm and T-warm antibodies. The results of this study suggest, but do not confirm, that B-cold antibodies benefit graft survival, while T-warm antibodies adversely influence graft survival. Transfusions and B-cold antibodies appear to influence graft survival by different mechanisms.

Antibody Formation↗

Deliberate donor-specific blood transfusions prior to living related renal transplantation. A new approach.

In order to select MLC incompatible one-haplotype related donor-recipient pairs that would achieve better graft survival and in an effort to alter the recipient immune response, 45 patients received three fresh blood transfuions from their prospective kidney donors. Recipient sensitization was evaluated by cross-match testing weekly sera obtained during and after the blood transfusions against donor T- and B-lymphocytes at 5 C (cold) and 37 C (warm). Thirteen (29%) of the 45 potential related recipients developed a positive warm T-cell cross-match or a persistent warm B-cell cross-match to their blood donor and related transplantation was not performed. Thirty-two (71%) patients had an appropriate negative cross-match to their blood donor. Thirty of these patients subsequently received kidneys from their blood donor. Ninety-seven per cent of the kidneys are functioning from one to 25 months with a single graft failure due to a patient discontinuing immunosuppressive medication. In addition to the excellent graft survival there was an unusually low incidence of rejection episodes in the recipients of kidneys from their blood donor so that the posttransplant course paralleled that of HLA-identical siblings. This approach may have future application with two-haplotype mismatched donor-recipient pairs, both related and unrelated.

Adult↗

Combined effects of HLA matching and age in renal transplantation.

Recipient age and matching for the HLA-A and B antigens each influence the graft survival rate of cadaver kidney transplants by approximately 10%. These two factors are cumulative and have a combined effect of nearly 20%. Thus, other factors that have a relatively weak influence on graft success may have a combined effect that makes their clinical consideration highly relevant.

Adolescent↗

Dominant effect of transfusions on kidney graft survival.

The number of pretransplant blood transfusions influences the graft survival of cadaver kidney transplants more than HLA-A and B matching, preformed lymphocytotoxic antibodies, or center variation. At 1 year the graft survival rate in patients with more than 20 packed cells transfusions was over 30% higher than that in nontransfused recipients (75 +/- 5% versus 41 +/- 2%, P less than 0.0001). Recipients with on packed cell transfusion had a 59 +/- 5% 1-year graft survival rate. Frozen blood and any transfusions given at the time of surgery were relatively ineffective. Pretransplant pregnancies had no significant effect on graft outcome. The improvement effect of transfusions was significant in each of the last four calendar years (1975, P less than 0.001; 1976, P less than 0.01; 1977, P less than 0.0001; 1978, P less than 0.0001). Yet, the percentage of nontransfused recipients has remained almost unchanged over the years. A preliminary survey of transplants done from January to April 1979 showed that one-third of the recipients had not been transfused. A change in transfusion policy is indicated to improve the results of cadaver kidney transplantation.

Antilymphocyte Serum↗

B cell antibodies and crossmatching.

Over 200 cadaver donor transplants were crossmatched against T and B lymphocytes at 5 and 37 C. Of 54 positive B cell crossmatches, one-half had cold antibodies and one-half had warm antibodies. The 1-year transplant survival was 58% for B-cold-positive crossmatches and 42% for B-warm-positive crossmatches. The B-warm-positive crossmatches, when subdivided into those with strong HLA-DR antibodies showed a 27% 1-year transplant survival rate. We conclude that B cell-positive crossmatches with HLA-DR antibodies are deleterious and that those with cold anti-IgM antibodies may enhance graft survival.

Absorption↗

The Lewis system and kidney transplantation.

A significant effect of Lewis antigens on cadaver kidney graft survival was found in 1,300 North American transplants. Lewis-negative recipients had a graft survival rate that was 8% lower than that of Lewis-positive recipients (P = 0.05). This effect of Lewis antigens was enhanced in patients at a high failure risk as determined by age, race, or transplant center. In patients older than 30 years, the effect of Lewis was 14% (P = 0.07), in non-Caucasians 12% (P = 0.07), in all grafts performed at centers with less than 50% overall 1-year graft survival 12% (P = 0.03), and in non-Caucasians that received transplants in centers with less than 50% overall graft survival it was 18% (p = 0.01). These data confirm previous results on the role of Lewis as a histocompatibility system in renal transplantation; furthermore, they demonstrate that the influence of Lewis is larger in patients at high risk.

Adult↗

HLA and cell-mediated immunity in HBsAg negative chronic active hepatitis.

In 20 patients with severe HBsAg negative chronic active hepatitis a significant association has been found between the HLA determinants A1, B8, and Dw3 and cell-mediated immunity directed against human liver specific lipoprotein in vitro. This observation induces further speculation that genetic immunoregulatory action might be involved in the pathogenetic mechanisms of chronic active hepatitis in vivo.

Adult↗