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Biomedical subjects

J C Scornik

Publications and source records attributed to J C Scornik.

At least 19 recordsLinked to original sources
PubMed1992

Hyperacute and acute kidney graft rejection due to antibodies against B cells.

Because of the perception of its uncertain clinical significance, the B cell crossmatch is not universally performed before renal transplantation. Even though sporadic cases of hyperacute rejection associated with B cell antibodies have been reported, doubts remain in light of other studies suggesting no effect on graft survival. This report describes 4 cases of graft rejection (3 hyperacute and 1 acute) that occurred in patients with anti-B-cell antibodies specific against donor HLA-DR or DQ antigens. Absence of anti-donor class I antibodies was confirmed in all cases by 2-color flow cytometry. Strong evidence for an antibody-mediated mechanism was found in one patient with anti-class I and anti-class II antibodies in serum transplanted with a class II mismatched kidney. In this case, only anti-class II antibodies were recovered in the eluate of the nephrectomy specimen. These four cases were compiled from three different institutions over a four-year period, which confirms the infrequent occurrence of these events. While anti-class II antibodies may not always be detrimental for graft survival, these results also confirm that they have the potential to cause hyperacute or acute graft loss. We conclude that the information provided by the B cell crossmatch should be available at the time that a decision to proceed with a renal transplant is made.

Adult↗
PubMed1992

Immunosuppression without prophylactic antilymphocyte preparations.

1. Triple-drug immunosuppression following third party transfusion can result in graft survival equal to protocols that employ prophylactic antilymphocyte preparations. 2. T1/2 was statistically improved in cadaveric and living-related donor grafts in the CsA era. 3. Patients 65 years and older had an excessive death rate. Younger groups were admixed. Extreme youth was not a risk factor. 4. Black recipients had excessive late graft loss. 5. Diabetic recipients had only a slight decline in graft and patient survival rates. 6. First and multiple graft recipients had similar transplant survival rates. 7. Delayed graft function remains costly in this immunosuppressive scheme.

Academic Medical Centers↗
PubMed1991

Intramolecular specificity of anti-HLA alloantibodies.

Recent descriptions of epitopes within HLA class I antigens recognized by mouse monoclonal antibodies are providing an antigenic map of such molecules. However, for transplantation purposes, it is crucial to understand the epitope specificity of alloantibodies. To investigate this issue, we performed sequential absorption/elution studies with serum from a broadly sensitized patient and homozygous typing cells (HTCs) which shared one HLA-A,B antigen with the patient. Antibody reactivity in the different eluates was measured by flow cytometry in a panel of 20 HTCs. These studies revealed two major findings: (a) There were multiple antibodies recognizing one HLA antigen. For example, there were 8 anti-B62 antibodies, 8 anti-B51, 5 anti-B57, 5 anti-B46, and 4 anti-B35. (b) The reactivity of most antibodies correlated highly with the presence of specific amino acids at a given position in the target HLA molecule. Such residues were absent in most HLA antigens not recognized by the antibody. Most of the target residues were located in the accessible alpha helices or connecting loops, but at least one antibody reactivity appeared to be influenced by residues located in the beta sheets. The HLA antigens evaluated in this study were those of the B5, B15, B17 cross-reactive group which have multiple epitopic sites. However, further studies are necessary to determine if alloantibodies directed to other HLA molecules will have a similar or more restricted degree of complexity.

Amino Acid Sequence↗
PubMed1991

HLA epitope matching. Contribution of matched residues to epitopes recognized by alloantibodies.

Applying absorption-elution techniques with homozygous typing cells and flow cytometry, a number of alloantibodies that recognized HLA-B62 but not B46 were identified. B62 and B46 are identical except in amino acids 66-76, which are probably recognized by the B62-specific antibodies. The patients who made these antibodies, however, had HLA antigens sharing amino acids 66-76 with B62, indicating that residues that are identical to the patient's own contribute to the antigenic determinants of foreign HLA molecules. Fine specificity analysis of most of these antibodies revealed that they recognized residues in the 66-76 segment in addition to other residues which were located in close proximity to this segment. We conclude that mismatched amino acid residues located in one part of the HLA molecule can interact with residues that are not different from those in the patient's own HLA molecules to form epitopes recognizable by alloantibodies. These findings should be helpful in improving our understanding of how to use current knowledge at the molecular level for the purpose of matching transplant donors and recipients.

Antibody Specificity↗
PubMed1990

Induction of erythrocyte HLA expression during interferon treatment and HIV infection.

Although HLA antigens are present on the surface membrane of most cells, erythrocytes express little or no HLA. Occasionally red cells from normal individuals or patients with certain diseases express elevated levels of these molecules. The reasons for such variations are currently not understood. We report here that the expression of very high levels of HLA on erythrocytes occurs in response to interferon alpha given as a therapeutic agent for viral hepatitis. Increased expression became apparent after the second or third week of treatment, peaked at 3-4 months, and decreased at the end of the treatment period. This chronology suggests that elevated HLA expression is originated during erythropoiesis and persists throughout the lifetime of the erythrocyte. Furthermore, erythrocyte HLA expression did not correlate with changes of plasma HLA or beta 2-microglobulin concentrations and was not affected by in vitro chloroquine treatment, ruling out the possibility that HLA was adsorbed from plasma. Increased expression of HLA on erythrocytes was also demonstrated in patients infected with the human immunodeficiency virus, a disease in which increased production of endogenous interferon has been previously documented. We conclude that high HLA expression in red cells occurs in response to persistent interferon stimulation. Further studies will determine if this effect can also be produced by interferon tau or other factors.

Adult↗
PubMed1990

Evaluation of individual specificities of class I HLA on platelets by a newly developed monoclonal antibody.

In order to quantify each specific HLA-A or -B antigen on platelets, a monoclonal antibody against HLA heavy chains was developed and designated as 2F2 monoclonal antibody. This monoclonal antibody reacted on Western blot with platelet HLA from each of 10 individuals with different HLA phenotypes and precipitated all 35S-methionine-labeled HLA-A and -B antigens from three different Epstein-Barr Virus--transformed lymphoblastoid cell lines. The results indicate that the 2F2 monoclonal antibody recognizes an epitope shared by different HLA-A and -B antigens. The quantitative variation of specific HLA antigens on platelets was then studied in nine different donors by isoelectric-focusing gel electrophoresis and immunoblot using the 2F2 monoclonal antibody. The results of our studies showed that the shared HLA antigens such as A2, B35, and B62, varied three- to fivefold among different individuals and individual HLA-A or -B antigen was not equally expressed on a person's platelets. The relative quantities of specific HLA-A and -B antigens on lymphocytes were also noted to be the same as those on platelets. The finding suggests that differential expression of HLA specificities may not be restricted to platelets but is a more general phenomenon including other nucleated cells.

Antibodies, Monoclonal↗
PubMed1989

Renal transplantation: a 20-year experience at the University of Florida.

Substantial gains have been made in both patient and graft survival during 20 years of transplanting kidneys at the University of Florida. The number of transplant recipients yearly has increased from six in 1966 to more than 100 in 1986. The use of immunosuppression reflects our evolving understanding of transplant immunology, with current morbidity and mortality rates considerably improved over those of the early years. This paper summarizes our transplantation experience over the past two decades.

Adolescent↗
PubMed1989

Incidental and purposeful random donor blood transfusion. Sensitization and transplantation.

We conducted a prospective study to gauge the frequency and degree of sensitization by transfusion and/or pregnancy in 797 candidates for first renal transplants. Sensitization was proportional to the number of blood transfusions. Multiple transfusions or a history of pregnancy without transfusions had similar effects on sensitization. The combination of transfusion and prior pregnancy resulted in sensitization of 1/3 of the candidates. Patients who were not sensitized and were accepted for 1-haplotype living-related donor grafts or first-cadaver donor grafts were transfused to receive a total of 5 units of packed red blood cells. Parous patients had an undue rate of antibody formation and alternate means of selecting and managing parous women are described. Nonparous candidates had a low rate of sensitization (8%) that did not prove an impediment to obtaining a transplant. Only 2% of prospective LRD graft recipients developed antibody against their intended donor. Transplant patients were generally managed with azathioprine and prednisone. One-haplotype LRD graft survival of protocol patients was 93.7% one year posttransplant, and 82.1% at 5 years. One-year CD graft survival was 77%. There was no reduction in graft survival when the interval between transfusion and transplantation exceeded one year. Random donor transfusion is effective in improving renal graft survival. Some recent multiinstitutional reports indicate a reduction or absence of the transfusion effect with current immunosuppression. Discarding blood transfusion as a preparation for transplantation may be ill-advised pending a prospective study.

Blood Transfusion↗
PubMed1989

Posttransplant antidonor antibodies and graft rejection. Evaluation by two-color flow cytometry.

The posttransplant production of antibodies against cryopreserved donor cells was studied in 50 consecutive cadaveric kidney graft recipients and in 23 additional patients selected for acute rejection. Serum was obtained twice weekly during the first 3 weeks posttransplant and then monthly for 6 months. IgM and IgG anti-T cell Abs were measured by 2-color flow cytometry. Results were analyzed in conjunction with the patients' demographics, previous sensitization, HLA-matching, posttransplant blood transfusions, incidence of delayed function, rejection episodes, and biopsy results. Antidonor antibodies, predominantly IgG, were detected in 19/48 (40%) of the patients proximate to the time of rejection. In contrast, antibodies were seen in only 2/22 (9%) of nonrejecting patients, and these antibodies were exclusively IgM. Younger patients were more likely to have antibody-mediated rejections. Cytotoxic antibody reactivity against panel cells developed or increased posttransplant in some patients, but it did not correlate with rejection. Previous sensitization and posttransplant transfusions favored the development of posttransplant panel reactivity but not of antidonor antibodies. Most rejections, including those associated with antidonor antibodies, were reversed by antirejection therapy. We conclude that antidonor antibodies are involved in a significant proportion of rejection episodes and that the damage induced does not necessarily culminate with loss of the graft.

Adult↗
PubMed1989

Prevention of transfusion-induced broad sensitization in renal transplant candidates.

Blood transfusions can induce broadly reactive anti-HLA cytotoxic antibodies, particularly in patients who have had previous transplants or pregnancies. To evaluate if HLA-matched transfusions were less immunogenic, renal transplant candidates at high risk of becoming sensitized were transfused with blood from partially or totally HLA-matched donors. The study was performed in multiparous patients who in addition had low level antilymphocyte antibodies detected by flow cytometry. Only 1/24 patients (4.2%) developed cytotoxic antibodies. Crossover studies were possible in 3 patients. In 2 patients the HLA-matched transfusions did not elicit a response, but the patients produced cytotoxic antibodies of broad reactivity when they were subsequently transfused with random donor blood. The third patient developed cytotoxic antibodies after transfusions mismatched for only one HLA-A,B antigen. Subsequent transfusions mismatched for a different antigen did not, in contrast, result in sensitization. These results demonstrate that HLA-matched transfusions, unlike regular and leukocyte-free transfusions evaluated in previous studies, can prevent sensitization in patients with a high probability of becoming untransplantable if transfused with random donor blood.

Antibodies↗
PubMed1988

Association between HLA phenotype and HLA concentration in plasma or platelets.

To understand the relationship between HLA phenotype and plasma or platelet HLA better, concentrations of plasma and platelet HLA were measured in 215 individuals of known HLA phenotypes. Precise quantitation of HLA antigens was achieved by means of an enzyme-linked immunoassay using the W6/32 monoclonal antibody and purified HLA molecules. The mean plasma and platelet HLA concentrations were 2.04 +/- 1.67 micrograms/ml (+/- SD, n = 215) and 11.28 +/- 4.65 fg/cell (+/- SD, n = 213), respectively. Statistical analysis of associations between HLA phenotypes and plasma HLA revealed that the mean plasma HLA concentration of individuals with HLA-A23 or HLA-A24 was 1.4 (p less than 0.002) or 1.9 (p less than 0.001) times higher than those without these two HLA antigens. Furthermore, the mean plasma HLA concentration of individuals who have HLA-A26 was 25% less than those without HLA-A26 (p less than 0.05). In contrast, the only association between HLA phenotypes and HLA concentrations of platelets was observed in HLA-B7-positive individuals. The mean platelet HLA concentration of HLA-B7 individuals was 27% higher than those without HLA-B7 (p less than 0.005). This finding is in accordance with previous observations made on red blood cells. The results indicate that the HLA concentrations in plasma are regulated, at least in part, by genetic factors that are different from those regulating platelet HLA.

Adolescent↗
PubMed1988

Evaluation of antibody synthesis in broadly sensitized patients.

This study was conducted to evaluate the rate of lymphocyte antibody synthesis in broadly sensitized patients. Antibody synthesis was estimated utilizing two approaches. In one, the time required by the antibodies to reach half their original values was determined by quantitating their levels by flow cytometry over periods of several months. In the other approach we measured the rate at which antibodies rose after inducing an artificial reduction by means of plasma exchanges. Patients not previously transplanted and not transfused during the study period showed low antibody synthesis and decreasing panel reactivity. In most previously transplanted patients panel reactivity did not change during the observation period. However, some patients displayed low antibody synthesis activity whereas others produced antibodies at a high rate. Extensive studies in one patient demonstrated active antibody synthesis even though he had not been transfused for more than two years. The results suggest that while frequent plasma exchanges can reduce antibody concentrations, concomitant use of immunosuppression may be needed only in patients shown to be actively producing antibodies.

Antibody Formation↗
PubMed1988

Late results of renal transplantation.

A total of 315 (64%) of 491 primary cadaver and living-related donor transplants performed from 1975 through 1984 were still functioning at 24 months. These selected patients were examined further to assess the impact of several risk factors on late graft and patient survival. Black recipients, patients with underlying diabetes mellitus or hypertension, patients with poor renal function at 24 months, and recipients of cadaver grafts had significantly poorer long-term graft survival. Age greater than or equal to 40, diabetes or hypertension, poor 24-month function, and cadaver donor transplantation were associated with poorer long-term patient survival. Considerable improvement in graft survival at 24 months was seen in 1980-1984 compared with the earlier period, coincident with our adoption of routine pretransplant random donor blood transfusion. In contrast, long-term graft survival in patients with functioning graft at two years did not improve significantly over the same period. Although living-related donor transplants showed greater graft and patient survival than cadaver donor grafts by univariate analysis, no such advantage was demonstrated by multivariate analysis.

Actuarial Analysis↗
PubMed1987

HLA-A2 epitopes recognized by alloantibodies from broadly sensitized patients.

Alloantibodies in broadly sensitized patients are difficult to characterize because they comprise mixtures with different specificities. By studying the ability of patients' sera to inhibit or enhance the binding of two anti-HLA-A2 monoclonal antibodies, BB7.2 and MA2.1, reactivity with A2 epitopes could be operationally defined. One group of patients had antibodies that inhibited the binding of both monoclonal antibodies. The inhibitory activity was removed by absorption with A2 positive cells but not with A28 or B17 positive cells. These alloantibodies apparently recognized the A2-Bw69 epitope also defined by the BB7.2 monoclonal antibody. In other patients, the inhibitory activity was removed by A2 and B17 positive cells, suggesting the involvement of the same epitope recognized by the MA2.1 monoclonal antibody. A third type of reactivity was detected in other patients. These alloantibodies enhanced the binding of BB7.2, inhibited MA2.1, and were absorbed by A2 and B17 positive cells indicating that the A2-B17 epitope was involved in these cases too. These studies underscore the potential value of monoclonal antibodies in dissecting the specificities of complex alloantibody mixtures.

Antibodies, Monoclonal↗