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Paul I Terasaki

Publications and source records attributed to Paul I Terasaki.

At least 19 recordsLinked to original sources
PubMed2007

Analysis of HLA class I specific antibodies in patients with failed allografts.

BACKGROUND: The goals of this study are first to determine the epitope specificity of donor specific antibody (DSA) in the serum of alloimmunized transplant patients with a failed renal graft; and second to understand the correlation between the development of DSA and nondonor specific antibody (NDSA). METHODS: The sera of 35 pretransplant panel reactive antibody (PRA)-negative patients with failed allografts were examined with single-antigen (SA) luminex beads to identify human leukocyte antigen (HLA)-A and -B antibodies. Potential HLA antibody epitopes were identified by using computer software and verified by absorption and elution from single-antigen cell lines. RESULTS: Twenty-seven patients developed donor-specific HLA-A and/or -B antibodies, while the remaining eight patients had only nondonor-specific HLA-A and/or -B antibodies. The DSA-positive patients also had a long list of NDSA. Sixty-eight percent of the reactions found in 27 recipients with DSA were attributable to 66 epitopes on the mismatched donor HLA molecule. All 39 NDSA in eight patients with only NDSA shared 17 epitopes within positive allele specificities. By absorption and elution using recombinant cell lines having a single HLA specificity, we confirmed the epitopes involved in three patients. CONCLUSION: Development of most NDSA in patients with failed allografts is likely due to sharing epitopes with DSA and/or other NDSA.

Antibody Formation↗
PubMed2006

HIV-positive renal recipients can achieve survival rates similar to those of HIV-negative patients.

BACKGROUND: Although patients positive for HIV were once thought to be unsuitable candidates for kidney transplantation, their increasing numbers with end-stage renal disease (ESRD) and the introduction of highly active antiretroviral therapy has indicated that they should no longer be excluded for transplantation. To counteract suggestions that human immunodeficiency virus (HIV) patients received suboptimal kidneys, we provide studies of kidneys transplanted from the same donor into patients with and without HIV. METHODS: United Network for Organ Sharing kidney transplant data between 1997 and 2004 were analyzed. Graft and patient survival of 38 HIV patients who had received a renal transplant were compared with the survival of 38 recipients who had received a graft from the same donor. RESULTS: The 38 HIV-positive recipients were younger (49.0 vs. 52.3 years, P=0.14) and had lower peak panel-reactive antibodies (PRA; 5.1% vs. 15.6%, P=0.07) when compared with their bilateral donor to HIV-negative recipients. Sirolimus was used more frequently in HIV patients than in non-HIV patients (36.8% vs. 23.7%, P=0.09). The serum creatinine at 1, 3, and 5 years posttransplantation were higher in HIV patients when compared to non-HIV patients. Although not statistically significant, graft survival was higher among HIV-positive patients compared with their negative controls (76.1% vs. 65.1% at 5 years, P=0.21), as was patient survival (91.3% vs. 87.3% at 5 years, P=0.72). More grafts failed due to death with a functioning graft than rejection in HIV-positive patients. CONCLUSION: This study supports the position that there is no longer an ethical question surrounding the use of kidneys for HIV-positive patients.

Female↗
PubMed2006

Frequency of MIC antibody in rejected renal transplant patients without HLA antibody.

Antibodies to MICA and MICB antigens were sought in the sera of 139 kidney transplant recipients. MICA*001, *002, *007, *008, and MICB*002 antigens were produced in Escherichia coli and then tested using enzyme-linked immunosorbent assay plates. Among 35 normal sera, 6% had MIC antibodies, and among 14 sera from pregnant women, 21% had MIC antibodies. Among 34 patients with functioning transplants with human leukocyte antigen (HLA) antibodies, 24% had MIC antibodies, and 19% of 32 patients without HLA antibodies had MIC antibodies. Among 46 patients who lost grafts with HLA antibodies, 26% had MIC antibodies, and among 27 failed patients without HLA antibodies, 37% had MIC antibodies. We conclude that antibodies to MIC are produced in the course of immunization by pregnancies and kidney transplants. They also occurred more frequently in rejected patients (30%) than in those with functioning grafts (21%).

Enzyme-Linked Immunosorbent Assay↗
PubMed2005

Detection of antibodies to HLA-DP in renal transplant recipients using single antigen beads.

With the development of single DP-antigen beads, antibodies to DP could clearly be segregated from other HLA antibodies. We studied 323 sera of patients from four different centers with functioning or rejected kidney grafts. DP antibodies were found in 5.1% of 138 patients with functioning grafts, and 19.5 % of 185 patients with rejected grafts (P<0.001)). 42.9% and 63.9% of the DP antibody positive patients had DR/DQ antibodies among the functioning and rejected group. Among patients who did not have Class I and DR/DQ antibodies, 13% of those who rejected a graft had DP antibodies, compared to 3.5% of patients with functioning grafts (P<0.05). DP 0301 had the highest specificity frequency in the rejected group. In conclusion, HLA-DP antibodies were detected at a higher frequency in patients who have rejected their grafts than those with functioning grafts. For regrafts, DP tissue typing is recommended to avoid presensitized DP alleles.

Antibody Specificity↗
PubMed2005

Predictive value of HLA antibodies and serum creatinine in chronic rejection: results of a 2-year prospective trial.

In this large collaborative study, 2,231 transplanted patients with functioning kidneys were tested for HLA antibodies, then examined 2 years later for graft survival. Among 478 patients with antibodies, 15.1% failed in 2 years, compared to 6.8% failure in 1,753 patients without antibodies (P=0.00000002). Cytotoxicity testing correlated better with outcome than flow cytometry or ELISA testing on HLA coated beads, possibly because it detected non-HLA antigens. When the patients were further broken down into those with serum creatinine at the time of testing of 0.5-1.9, 4.4% of antibody patients failed at 2 years, compared to 4.3% of patients without antibodies. This 0.1% difference increased among patients with serum creatinine values of 2.0-2.9 to 17.9%, and among those with 3.0-3.9 to 16.3%. We conclude that HLA antibodies posttransplantation is predictive of subsequent graft failure, and its predictive value can be enhanced among patients with higher serum creatinine values.

Antibodies↗
PubMed2005

Frequency and clinical implications of development of donor-specific and non-donor-specific HLA antibodies after kidney transplantation.

The involvement of immunologic and nonimmunologic events in long-term kidney allograft failure is difficult to assess. The development of HLA antibodies after transplantation is the witness of ongoing reactivity against the transplant, and several studies have suggested that the presence of HLA antibodies correlates with poor graft survival. However, they have not discriminated between donor-specific (DS) and non-specific (NDS) antibodies. A total of 1229 recipients of a kidney graft, transplanted between 1972 and 2002, who had over a 5-yr period a prospective annual screening for HLA antibodies with a combination of ELISA, complement-dependent cytotoxicity, and flow cytometry tests were investigated; in 543 of them, the screening was complete from transplantation to the fifth year postgrafting. Correlations were established between the presence and the specificity of the antibodies and clinical parameters. A total of 5.5% of the patients had DS, 11.3% had NDS, and 83% had no HLA antibodies after transplantation. NDS antibodies appeared earlier (1 to 5 yr posttransplantation) than DS antibodies (5 to 10 yr). In multivariate analysis, HLA-DR matching, pretransplantation immunization, and acute rejection were significantly associated with the development of both DS and NDS antibodies and also of DS versus NDS antibodies. The presence of either DS or NDS antibodies significantly correlated with lower graft survival, poor transplant function, and proteinuria. Screening of HLA antibodies posttransplantation could be a good tool for the follow-up of patients who receive a kidney transplant and allow immunosuppression to be tailored.

Adult↗
PubMed2005

Living-unrelated donors yield higher graft survival rates than parental donors.

BACKGROUND: Living-unrelated donors (LURD) have been shown to yield kidney graft survival rates equivalent to that of related donors. Here, we show that in three diseases, LURDs supply grafts that survive at a higher rate than parental or offspring donors. METHODS: We analyzed 111,643 first adult kidney transplants from the United Network for Organ Sharing database performed between 1991 and 2003 by Kaplan-Meier curves, log-rank tests, and Cox proportional hazard tests. RESULTS: Five-year kidney graft survival rates in patients receiving grafts from LURD, parental, and offspring donors were 75.4%, 74.3%, and 75.7% among patients with typical original diseases excluding three diseases. In focal glomerulosclerosis (FGS), the corresponding results were 87.4%, 70.1%, and 81.6%. In polycystic kidney disease (PC) rates were 86.4%, 78.6%, and 85.3%, and in diabetes mellitus (type 1 DM) rates were 75.9%, 69.8%, and 70.5%. Parental donors yielded significantly lower graft survival rates than LURDs in all three diseases. Although statistically significant differences were lost in the Cox tests, functional graft survival showed significantly lower graft survival rates from parental donors compared with LURDs, suggesting that donor age was a significant factor. CONCLUSIONS: If living donors are considered for kidney transplantation into patients with FGS, PC, or type 1 DM, grafts from LURD are preferred over parental and offspring donors. Although genetic susceptibility of parental and offspring donor grafts may be a factor, the simple donor age factor probably results in lower survival of parental donor grafts. Lower survival of offspring donor grafts may suggest genetic susceptibility because such donors were, in general, younger than in LURD grafts.

Cadaver↗
PubMed2005

Human leukocyte antigen antibodies for monitoring transplant patients.

Human leukocyte antigen (HLA) antibody-mediated hyperacute rejection has dramatically decreased since the clinical introduction of crossmatch technology. However, the role of HLA antibody in acute and chronic rejection remains unclear. In this article, we cite publications to show the correlation between HLA antibody and allograft rejection. Potential pathological mechanisms of antibody-mediated rejection are also proposed and the rationale of commonly used HLA antibody detection techniques are introduced. The advantages and disadvantages of these technologies are further discussed in detail. We conclude that owing to the recent availability of improved antibody detection methods, a causal relationship between HLA antibodies and allograft rejection is now considered to exist.

Graft Rejection↗
PubMed2005

Humoral theory of transplantation: further evidence.

In the two and a half years following our initial paper on the humoral theory of transplantation, many publications have emerged in support of the hypothesis, with no studies in opposition. It is accepted that the role of antibodies is incontrovertible in hyperacute rejection, although what fraction of acute rejection is humoral remains to be determined. A recent large-scale prospective trial showing that transplant patients with antibodies have twice the failure rate as those without antibodies suggests that chronic rejection is also caused by antibodies. Together with serum creatinine, HLA antibodies are, therefore, the best predictor of graft function in kidney patients.

Antibody Formation↗
PubMed2005

Humoral theory of transplantation: mechanism, prevention, and treatment.

We discuss the potential mechanisms of antibody-induced primary endothelium injury, which includes complement-dependent pathway (membrane attack complex formation, recruitment of inflammatory cells, and complement-complement receptor-mediated phagocytosis) and complement independent pathway antibody-dependent cell cytotoxicity. Secondary to endothelium injury, the following pathological reactions are found to be responsible for progressive tissue injury and final graft function loss: platelet activation and thrombosis, pathological smooth muscle and endothelial cell proliferation, and humoral and/or cellular infiltrate-mediated parenchyma damage after endothelium injury. We also introduce three categories of therapeutic strategy in the prevention and treatment of antibody-mediated rejection: (1) inhibition and depletion of antibody producing cells (immunosuppressants, antilymphocyte antibodies, splenectomy); (2) removal or blockage of preexisting or newly developed antibodies (immunoadsorption, plasmapheresis/plasma exchange, intravenous immunoglobulin); and (3) impediment or postponement of antibody-mediated primary and secondary tissue injury (anticoagulation, glucosteroids). In conclusion, because alloantibodies have destructive effect on allografts, alloantibody monitoring becomes extremely important. It will help clinicians to determine a patient's humoral responses against allograft and will therefore direct clinicians to optimize and/or minimize immunosuppressive drug therapy.

Animals↗
PubMed2004

Screening of high cytotoxic tumor killer cells using a sensitive adherent target detachment assay.

Screening of high cytotoxic tumor killer cells is of great importance in adoptive immunotherapy. Here, we describe a more sensitive assay, as compared to traditional 51Cr- or Calcein-release assay, to measure cytolytic activity of killer cells. This adherent target detachment (ATD) assay is carried out in microwells of Terasaki tissue culture trays using adherent tumor cells as targets. Target tumor cells are seeded at the concentration of 300-400 cells/well and incubated overnight to allow for the adhesion of cells to the plastic surface of the wells. Effector cells were added at various effector: target (E:T) ratios, and incubated for 24 h. During incubation, dead target cells became nonadherent and together with the added effector cells were removed by washing. The remaining viable adherent target cells were stained with acrydine orange contained in the quencher and optically counted by microcomputer. A notable dose-dependent killing on target tumor cells was reproducibly obtained by tested effector cells. Cytotoxic activities of most effector cells were significantly higher in the 24-h ATD assay than those of concordant 4-h target cell lysis test. Chloroquine (chq) inhibition test in the 24-h ATD assay showed negative or weak inhibition on cytotoxicity against adherent targets. Linear regression analysis also manifested the lack of a close correlation between 4- and 24-h target cell lysis tests, indicating these two assays measured different killing activities of the same effector cells. Because of its high sensitivity and reproducibility, this semiautomatic 24-h assay with computerized fluorescence measurement system could serve as a sensitive screening assay to select high cytotoxic tumor killer cells in adoptive immunotherapy.

Cell Adhesion↗
PubMed2004

Correlation between human leukocyte antigen antibody production and serum creatinine in patients receiving sirolimus monotherapy after Campath-1H induction.

BACKGROUND: In this study, we determined whether Campath-1H induction followed by sirolimus monotherapy inhibited alloantibody production in renal transplantation. Second, we evaluated the correlation between human leukocyte antigen (HLA) antibody production and serum creatinine levels. METHODS: Sera were taken 1 to 24 months after transplantation from 24 patients treated with Campath-1H and sirolimus and tested for serum creatinine and HLA-specific antibody by using flow cytometry and enzyme-linked immunosorbent assay. RESULTS: Ten (42%) of the 24 patients treated with Campath-1H and sirolimus produced HLA antibodies. Six of these 10 developed both donor-specific antibodies (DSAs) and non-donor-specific antibodies (NDSAs), whereas only NDSAs were detected in the other four patients. In patients with biopsy-diagnosed humoral rejection (C4d+), serum levels of both DSA and NDSA significantly correlated with patient serum creatinine levels. Rejection treatment successfully reduced both DSAs and NDSAs and reversed humoral rejection. CONCLUSIONS: The numeric relationship between serum creatinine and DSA levels suggests a causal relationship between alloantibody and transplant rejection.

Alemtuzumab↗
PubMed2004

Predicting kidney graft failure by HLA antibodies: a prospective trial.

HLA antibodies have been shown to be associated with late graft loss of organ transplants in prior studies. Recently they were even shown to appear years BEFORE rejection. (1) An international cooperative study of 4763 patients from 36 centers was undertaken to determine the frequency of HLA antibodies in patients with functional transplants. The overall frequency of HLA antibodies among kidney transplant recipients was 20.9%; 19.3% in the liver, 22.8% in the heart, and 14.2% in the lung. Patients treated with CsA-MMF had significantly lower antibodies (9.8%) than those treated with CsA-Aza (18.1%) (0.00008). (2) Second, a prospective trial was performed in 23 kidney transplant centers to determine whether HLA antibodies could predict failures within 1 year. Among the 2278 patients followed up, 91 grafts failed and 34 patients died. Of 500 patients who had HLA antibodies, 6.6% failed compared with 3.3% among 1778 patients without antibodies (p = 0.0007). Among 244 patients who made de novo antibodies, 8.6% failed compared with 3.0% failures among 1421 patients who did not make antibodies (p = 0.00003). Death occurred in 1.5% of patients and was not associated with antibodies. Thus, after 1 year in this prospective trial, patients with HLA antibodies had graft failure at a significantly higher rate than those without antibodies.

Antibodies↗
PubMed2004

An analysis of the OPTN/UNOS Liver Transplant Registry.

Based on data reported to the OPTN/UNOS Liver Transplant Registry between 1988-2004: 1. There was a very small difference in 5-year graft survival rates comparing living and deceased donors in adult (4.3%) and pediatric patients (2.4%). 2. Although graft survival rates of split liver transplants were lower than whole liver grafts before 1998, 5-year graft survival results of more recent split grafts (65.8%) have become comparable to those of whole liver grafts (66.5%). Among recipients in good condition, split (67.7%) and whole grafts (70.0%) yielded equivalent survival rates. 3. Lower graft survival rates were noted in ABO incompatible grafts, non-heartbeating donors, regrafted patients, and recipients who were in the ICU before transplantation. 4. There was no recipient gender effect on liver transplant outcome. 5. Primary disease distributions were different for different races. Among adult patients, the largest fraction of white patients had alcoholic cirrhosis. Among Asians, Type B cirrhosis was most frequent. Among pediatric patients, biliary atresia constituted the majority of patients. Most of the patients with alpha-1 antitrypsin deficiency were white. Autoimmune hepatitis was most frequently found among black patients. 6. Although 5-year graft survival of black patients (60.2%) was lower than whites (68.1%), Hispanics (67.6%), and Asians (68.0%), black recipients with PBC (73.3%) and PSC (69.9%) had graft survival rates similar to those of whites (78.1%) (73.6%) and Hispanics (75.3%) (77.1%). 7. Zero HLA-A,-B,-DR mismatched livers had very rapid early failures. HLA matching correlated with graft survival in autoimmune hepatitis patients, but not in cirrhosis patients. 8. Short-term graft survival for liver transplants has improved steadily since 1990. However, long-term graft survival after the first year actually declined over time. 9. In adult transplants, 5-year graft survival of autoimmune-related diseases, PBC (77.3%), PSC (73.3%), AIH (74.2%) yielded higher graft survival rates than those of hepatitis B (71.5%) and C (63.2%). 10. In pediatric patients, 5-year survival of biliary atresia (75.4%), autoimmune cirrhosis (70.8%), and alpha-1-antitrypsin deficiency (85.0%) had high graft survival rates, except for acute liver failure (61.6%). 11. Hepatitis C recurrence is now one of the major causes of graft failure in adults. Thrombosis is a major factor in graft failure for pediatric transplants.

ABO Blood-Group System↗
PubMed2004

Heart transplantation in the United States 2004.

The limited availability of donated hearts is not sufficient to meet the needs of increasing numbers of heart transplant candidates. Thus, it is important to find the best recipient for each donated heart in order to achieve the best graft and patient survival. We investigated heart transplant outcomes in the US and the factors that influence them. We present information regarding 36,277 heart transplants reported to the OPTN/ UNOS Registry from January 1988-October 2004. The annual number of transplants ranged between 2,057-2,363 during the past 14 years and has not increased since 1990. One- and 5-year graft survival rates have gradually increased and have reached 87% and 72%, respectively, for adult recipients. Non-immunological factors, such as the circumstance of the donor's death, cause of death and ischemic time, the recipient's race, age, original disease, infection, systemic cerebro-vascular disease, whether or not they were on life support, renal function etc, significantly impacted on graft survival. Immunological factors, such as previous transfusion, previous transplantation, HLA mismatches, sensitization status, rejection episodes before discharge or within one year after transplant, were associated with lower graft survival rates. In conclusion, in order to achieve the best possible outcome for heart transplant patients, we must first find the most suitable candidate for an available donated heart; secondly, we must optimize immunosuppressive regimens and other medical and surgical therapies to prevent graft rejection and transplant-related complications.

Adolescent↗