HLA-DR Matching Research Articles

Class II HLA Epitope Matching—A Strategy to Minimize De Novo Donor-Specific Antibody Development and Improve Outcomes

De novo donor-specific antibody (dnDSA) develops in 15–25% of renal transplant recipients within 5 years of transplantation and is associated with 40% lower graft survival at 10 years. HLA epitope matching is a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize epitope mismatches at 395 potential HLA-DR/DQ/DP conformational epitopes for 286 donor–recipient pairs. Epitope specificities were assigned using single antigen HLA bead analysis and correlated with known monoclonal alloantibody epitope targets. Locus-specific epitope mismatches were more numerous in patients who developed HLA-DR dnDSA alone (21.4 vs. 13.2, p < 0.02) or HLA-DQ dnDSA alone (27.5 vs. 17.3, p < 0.001). An optimal threshold for epitope mismatches (10 for HLA-DR, 17 for HLA-DQ) was defined that was associated with minimal development of Class II dnDSA. Applying these thresholds, zero and 2.7% of patients developed dnDSA against HLA-DR and HLA-DQ, respectively, after a median of 6.9 years. Epitope specificity analysis revealed that 3 HLA-DR and 3 HLA-DQ epitopes were independent multivariate predictors of Class II dnDSA. HLA-DR and DQ epitope matching outperforms traditional low-resolution antigen-based matching and has the potential to minimize the risk of de novo Class II DSA development, thereby improving long-term graft outcome.

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HLA matching in kidney transplantation is a major factor in long term survival of the graft. In Saudi Arabia, the majority of deceased donors (DD) are non-Saudi, making it difficult to achieve minimal HLA mismatches between the donor and the recipient. The aim of this study was to analyze HLA types of 200 DD and compare it with that of the Saudi population. This is a retrospective study analyzing HLA types of the last 200 deceased donors processed at King Abdulaziz Medical City, Riyadh. Results of the HLA types of all donors were compared with HLA types form our control panel of healthy Saudi cohort. HLA types were significantly different between the deceased donor group and the Saudi cohort. In all deceased donors, we never achieved a recipient who is 6/6 HLA zero mismatches. The major differences in HLA types were in HLA-A ∗ 02 (14% in DD vs 30% in Saudi controls), B ∗ 15 (16% in DD vs 5% in Saudi controls), B ∗ 40 (9% in DD vs 2% in Saudi controls), B ∗ 50 (4% in DD vs 19% in Saudi controls), DRB1 ∗ 14 (5% in DD vs 1% in Saudi controls), DRB1 ∗ 15 (21% in DD vs 13% in Saudi controls) and in DRB1 ∗ 04 (10% in DD vs 19% in Saudi controls). As most of our DD are non-Saudis this makes it difficult to match for HLA-A, B and DR. HLA-DR matching should be attempted nationwide by adopting different strategies including typing donors centrally and distributing results to all centers, agreeing on a national point system for allocating DD organs.

HLA-DR Matching in Organ Allocation: Balance Between Waiting Time and Rejection in Pediatric Kidney Transplantation

HLA-DR Matching in Organ Allocation: Balance Between Waiting Time and Rejection in Pediatric Kidney Transplantation

Association of human cytomegalovirus viremia with human leukocyte antigens in liver transplantation recipients

Human cytomegalovirus (HCMV) reactivation is a common complication after liver transplantation (LT). Here, we investigated whether human leukocyte antigen (HLA)-matching was related to HCMV infection and subsequent graft failure after LT for hepatitis B virus cirrhosis. This retrospective study reviewed 91 LT recipients. All the patients were grouped according to HLA-A, HLA-B, and HLA-DR locus matching. Clinical data were collected, including complete HLA-typing, HCMV viremia, graft failure, and the time of HCMV viremia. HLA typing was performed using a sequence-specific primer-polymerase chain reaction kit. HCMV was detected by pp65 antigenemia using a commercial kit. The incidence of HCMV infection post-LT was 81.32%. Graft failure was observed in 16 of 91 (17.6%) patients during the 4-year study. The incidence of HCMV viremia was 100% (5/5), 91.4% (32/35), and 72.5% (37/51) in HLA-A two locus, one locus, and zero locus compatibility, respectively. Nevertheless, the degree of the HLA-A, HLA-B, or HLA-DR match did not influence the time of HCMV viremia, graft failure, or the time of graft failure after a diagnosis of HCMV viremia (all P > 0.05). An interesting discovery was that the risk of HCMV viremia tended to be higher in patients with better HLA-A compatibility. Graft failure, time of HCMV viremia, and graft failure after a diagnosis of HCMV viremia appear to be independent of HLA allele compatibility.

HLA-DR Matching in Organ Allocation

To determine the impact of HLA-DR mismatching on rejection, graft survival, and sensitization in a local allocation system that emphasizes donor quality rather than HLA antigen matching for pediatric patients and to determine the likelihood of finding an appropriate donor based on HLA-DR mismatch. Retrospective cohort study. A single institution. A total of 178 patients younger than 21 years who underwent kidney transplantation with daclizumab induction between 1997 and 2006. The association between HLA-DR mismatching and rejection or graft survival was determined using survival analysis. Sensitization was defined as a posttransplantation panel reactive antibody level greater than 0% in patients with a pretransplantation level of 0%. Median follow-up was 4.1 years (interquartile range, 2.1-6.1 years). One- and 5-year graft survival rates were 97% and 82%, respectively. HLA-DRB1 mismatches were a significant risk factor for rejection; patients with 1- or 2-HLA-DRB1 mismatches had 1.7 times greater odds of rejection than those with 0-HLA-DR mismatches (P = .006). HLA-DRB1 mismatching was not a significant risk factor for either graft failure or sensitization, but history of rejection was an independent predictor of graft failure (hazard ratio, 7.7; P = .01) and sensitization (odds ratio, 9.7; P = .001). Although avoiding HLA-DRB1 mismatching reduces rejection, the probability of finding ABO-matched local donors younger than 35 years without DR mismatches was extremely low. Although avoiding HLA-DRB1 mismatching is beneficial, the likelihood of finding an HLA-DRB1-matched donor should also be considered in donor selection.

Association of Mismatches for HLA-DR With Incidence of Posttransplant Hip Fracture in Kidney Transplant Recipients

Bone fractures are a frequent complication after kidney transplantation, for which various predisposing factors have been identified. It has been suggested that human leukocyte antigen (HLA) mismatch increases the risk. Data on hip fractures occurring in the first 5 years posttransplant were analyzed among kidney transplants from deceased donors performed between 1995 and 2008 and reported to the Collaborative Transplant Study. In the 20,509 patients analyzed, the cumulative rate of hip fracture by year 5 posttransplant was 0.85%. Cox regression analysis identified the following risk factors: female recipients aged 40 to 59 years (hazard ratio [HR] 2.26, P=0.029), female recipients 60 years or older (HR 5.14, P<0.001), male recipients 60 years or older (HR 2.39, P=0.028), and donor age more than or equal to 60 years (HR 1.75, P=0.009). Using the rate of fractures in recipients with zero HLA-DR mismatch as the reference, the risk of hip fracture increased for grafts with one HLA-DR mismatch to HR 1.85 (95% confidence interval [CI] 1.18-2.89, P=0.007) and with two HLA-DR mismatches to HR 2.24 (CI 1.25-4.02, P=0.007). There was a significant association between the number of HLA-DR mismatches and the diagnosis of osteoporosis 5 years after transplantation: one HLA-DR mismatch risk ratio 1.26 (CI 1.12-1.43, P<0.001) and two HLA-DR mismatches risk ratio 1.45 (CI 1.20-1.74, P<0.001). The risk of hip fracture after kidney transplantation seems to be markedly exacerbated by HLA-DR mismatching. These findings add to the growing base of evidence that HLA-DR matching influences morbidity after kidney transplantation.

HLA matching for organ transplantation… Why not?

HLA matching for organ transplantation… Why not?

Pre-kidney-transplant blood transfusions do not improve transplantation outcome: a Dutch national study

Female renal transplant candidates are prone to be sensitized by prior pregnancies, and undetected historical sensitization might decrease transplantation outcome. Hypothesis of our study was that pre-transplant blood transfusions (PTFs) can elucidate historical sensitization and that the avoidance of the associated antigens can improve transplantation outcome. Data from all female non-immunized renal transplant candidates who received a random PTF (rPTF) (n = 620), matched PTF (mPTF) (one HLA-A and B and one HLA-DR match) (n = 86) or donor-specific blood transfusion (DST) (n = 100) between 1996 and 2006 were collected. Complement-dependent cytoxicity was used to detect anti-HLA antibodies. Sensitization and transplantation outcomes after a PTF were analyzed. Non-immunized female renal transplant recipients who did not receive a PTF were used as the control group. In 165 patients, anti-HLA antibodies (IgG) were detected after the PTF. Both historical and primary sensitizations were found. A DST induced donor-specific anti-HLA antibodies in 25% of the DST recipients. Our policy did not improve transplantation outcome in recipients of a kidney from a deceased donor (n = 368) or in recipients of a living donor [DST (n = 49) and mPTF (n = 66)]. A PTF did elucidate historical sensitization but induce primary sensitization as well. No beneficial effect of PTFs on transplantation outcome was found, and PTFs with the intention to detect historical sensitization are therefore not suggested.

HLA-DR-matched Parental Donors for Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-risk Acute Leukemia

The immunomodulating effect of human leukocyte antigen (HLA)-DR and the central role of CD4 T cells in alloimmunity provide clues suggesting that HLA-DR-matched, partially mismatched related donors could be feasible alternative donors of allogeneic hematopoietic stem cells for transplantations (allo-HSCT). We describe our experience with allo-HSCT in eight patients with high-risk acute leukemia; donors included one of each of the parents. Among the eight patients, seven were identical HLA-DR matches with the donors. The stem cells were not manipulated in vitro. Graft-versus-host disease (GVHD) prophylaxis consisted of antithymocyte globulin, cyclosporine, and methotrexate. All patients had successful trilineage engraftment. Only one patient had grade 2-4 acute GVHD. Two patients died before day +100 due to complications. At the end of follow-up, four patients had survived for 18-48 months and three are alive and without relapse. Our results suggest that HLA-DR fully-matched parents are feasible alternative donors for allo-HSCT in patients with high-risk acute leukemia under an intensive conditioning regimen.

Multitransplantation der Nieren: Operationstechnik, Ergebnisse, Komplikationen

Third renal transplants were performed in 31 patients (25 men and 3 women: mean age 33 +/- 11 years) with terminal renal failure. Surgical complications occurred in four of them. Acute rejection crises were frequent (48%). In three cases acute humoral vascular rejection led to loss of the grafted kidney. One patient died within 3 months. The proportion of functioning transplants was 83% at 3 months, 59% at 1 year and 20% at 5 years. Such factors as the concentration of panel-reactive antibodies, a history of previous acute humoral rejection crises or the timing of the previous transplant loss had no influence on the prognosis of the new graft. After a mean observation period of 35, 4 months patients whose HLA-DR antigens matched those of the donor at one or two loci had a markedly higher proportion of functioning renal transplants (69% and 64%, resp.) than patients without HLA-DR compatibility (0%; P less than 0.01). These results indicate that a third renal transplant does not carry any increased perioperative risk, and that the proportion of functioning transplants is good in the short term, though the long-term results are poor. Prolonged survival of the renal transplant can be expected only if there is an optimal HLA-DR match between donor and recipient.

Human Leukocyte Antigen-DR Matching Improved Skin Graft Survival From Transgenic Pigs to Accommodate SCID Mice Reconstituted With Human Peripheral Blood Mononuclear Cells

The shortage of human organs has encouraged scientists to develop genetically modified pigs for xenotransplantation, such as CD55 or CD46, and CD59 transgenesis as well as α-galactosyl transferase gene knockouts. In allotransplantation, the match of human leukocyte antigen class II (HLA-II) may improve graft survival although the role of HLA-II in xenotransplantation is unknown. HLA-II transgenic pigs, including DP, DQ, and DR, have been successfully generated and HLA-DR15 + transgenic pig skin pieces grafted onto severe congenital immunodeficiency (SCID) mice reconstituted intraperitoneally with HLA-DR15 + or HLA-DR15 − human peripheral blood mononuclear cells (hPBMCs). This study sought to develop an animal model to evaluate the effects of HLA-DR matching on xenograft survival. Human CD4 + and CD8 + were detected from days 7 to 29 after hPBMC reconstitution in SCID mice. Both CD4 + and CD8 + cells of HLA-DR15 − reconstituted SCID mice were significantly higher at day 29 postgrafting compared with HLA-DR15 + reconstituted SCID mice. An HLA-DR15 + transgenic pig dermal graft survived and integrated into SCID mice reconstituted with hPBMCs/HLA-DR15 + as proven by the histopathological finding that the collagen layer remained intact with little lymphocytic response. In contrast, the transgenic pig dermal graft showed more collagen disruption as well as mild to moderate lymphocytic infiltration when reconstituted in an hPBMC/HLA-DR15 − SCID mouse. The results suggested that HLA-DR matching eased xenograft rejection; however, it was not yet clear that the response was mediated by T cells.

Antibodies against MICA Antigens and Kidney-Transplant Rejection

Good HLA-A, HLA-B, and HLA-DR matches do not guarantee rejection-free renal transplantation. Some kidney transplants fail despite such matches, suggesting that other antigens might be targets for rejection. Major-histocompatibility-complex (MHC) class I-related chain A (MICA) antigens are polymorphic and can elicit antibody production. We sought to determine whether an immune response to MICA antigens might play a role in the failure of kidney allografts. Pretransplantation serum samples from 1910 recipients of kidney transplants from deceased donors were tested for anti-MICA antibodies with an assay in which single MICA antigens were attached to polystyrene microspheres. Antibodies against MICA alleles were detected in 217 of the 1910 patients (11.4%). The presence of MICA antibodies was associated with renal-allograft rejection. The mean (+/-SE) 1-year graft-survival rate was 88.3+/-2.2% among recipients with anti-MICA antibodies as compared with 93.0+/-0.6% among recipients without anti-MICA antibodies (P=0.01). Among recipients of first kidney transplants, the survival rate was even lower among MICA antibody-positive patients (87.8+/-2.4%) than among MICA antibody-negative recipients (93.5+/-0.6%, P=0.005). In addition, the association of MICA sensitization with reduced graft survival was more evident in kidney-transplant recipients with good HLA matching: among 326 recipients who received well-matched kidneys (0 or 1 HLA-A plus HLA-B plus HLA-DR mismatch), sensitization against MICA was associated with poorer allograft survival (83.2+/-5.8% among those with anti-MICA antibodies vs. 95.1+/-1.3% among those without such antibodies, P=0.002). Presensitization of kidney-transplant recipients against MICA antigens is associated with an increased frequency of graft loss and might contribute to allograft loss among recipients who are well matched for HLA.

The Predictive Value of HLA-DR Matching and Cytokine Gene Polymorphisms in Renal Allograft Acute Rejection: a Living-unrelated Donor (LURD) Study.

In addition to Human Leukocyte Antigens (HLA) compatibility, gene polymorphism in cytokines might be important in the quality of allogeneic immune response. In this study HLA-DR matching and a number of cytokine gene polymorphisms have been evaluated in occurrence of acute rejection after living-unrelated donor (LURD) kidney transplantation. A total of 42 renal transplants that were performed at Hashemi Nejad Kidney Hospital (Tehran/Iran) and then followed up for 3 months post-transplantation were included in our study. Using PCR-SSP, HLA-DR alleles (DR1-18) of recipient and donor pairs and gene polymorphisms in TNF-, TGF-1, IL-10, IL-6, and IFN- of recipients were determined. Acute rejection was observed in 11(26.2%) of 42 renal recipients. The frequency of one and two HLA-DR mismatches in rejector and nonrejector groups were 2(18.2%), 9(81.8%) and 13(41.9%), 17(54.8%) respectively. HLA-DR incompatibility was not significantly higher in rejector (1.820.40) than nonrejector (1.520.57) recipients (P=0.069) and more than half of nonrejectors had completely mismatched HLA-DR antigens with their donors. Polymorphisms associated with all the cytokines mentioned above were found to have no correlation with acute rejection. Regarding to high frequency of HLA-DR mismatching in nonrejector group, we can postulate that the immunogenecity of LURD renal transplant is not similar to the cadaveric one, and predictive value of HLA-DR mismatching for acute rejection is not as reliable as in cadaveric transplant. Although, there is no doubt about influence of HLA compatibility on allograft survival. In addition, we failed to demonstrate further association between combined recipient cytokine genotypes and HLA-DR matching with acute rejection in this study. Thus, we conclude that a more detailed immunogenetic profile is necessary to predict transplant outcome or immunosuppression tailoring.

The Gene Locus Distribution of HLA in the Chinese Population by High Resolution Typing of HLA-A,B,C,DR,DQ and Its Effect on Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (AHSCT)can potentially cure a variety of hematopoietic and congenital metabolic disorders. Ideally, one would hope to find identical unrelated donors who are genotypically identical to the patients at all HLA loci. To explore distribution of HLA gene subsites in the Chinese population and its effect on AHSCT. High resolution typing of HLA-A,B,Cw,DR,DQ were performed on 101 cases from the data base of China Marrow Donor Program (CMDP) donors and 76 patients (ALL 23cases, CML 32cases, AML 23cases)by using PCR-SSP and PCR-SSO. The HLA subsites with highest gene frequency were A*0201, A*0207, A*1101, A*2402, B*4001,B*4601, C*0102, C*0702, DR*0901, DR*1202,DQ*0301and DQ*0303(PF>0.2). The subsites with secondary high frequency were A*3101,A*3303,B*1301,B*1302,B*1501, B*5101,B*5801,C*0303,C*0304,C*0602,C*0801, DR*0405, DR*0406,DR*0701,DR*0803, DR*1501,DQ*0202,DQ*0302,DQ*0401, DQ*0502, DQ*0601(PF>0.1). The phenotypic frequency of A*1101,B*4601,C*0102,DR*0901, DQ*0303 in the Chinese population was as high as 0.38, Among which B*4601and DR*0901 were the single allele with highest frequency. The gene locus in HLA with linkage disequilibrium were A*0207-B*4601- DR*0901-C*0102-DQ*0301or0303;A*0201-B*4601-DR*0405 or DR*0803- C*0102-DQ*0302orDQ*0502;A*3001-B*1302-DR*0701-C*0602-DQ*0202 and A*3303- B*5801-DR*0901-C*0302-DQ*0303 or DQ*0302, respectively. CMDP demonstrated the effect of HLA-A and B allele matching on the development of severe acute GVHD and on the overall survival rate. HLA-DR matching are less effective than classIfor clinical outcomes. Additionally, the HLA-C mismatch was found to have a synergistic effect on the acute GVHD and survival rate when another HLA locus mismatch coexisted. Our results demonstrated that the frequency distribution of HLA gene subsites is important for selecting more suitably matched donor for HSCT and is helpful for making donor recruitment strategy. As the HLA-Cw played important role on aGVHD occurrence and the failure of BMT, more attention should be paied on HLA-Cw allele in clinical HSCT.

HLAMatchmaker: A Molecularly Based Algorithm for Histocompatibility Determination. V. Eplet Matching for HLA-DR, HLA-DQ, and HLA-DP

This report describes the design of the eplet version of HLAMatchmaker to determine class II compatibility at the structural level. This matching algorithm is based on the hypothesis, developed from molecular modeling of crystallized antigen-antibody complexes, that functional epitopes are represented by patches of surface-exposed nonself-amino acid residues surrounded by residues within a 3-Å radius. Patch determinations with a molecular viewer of crystalline structural models downloaded from the Entrez Molecular Modeling Database Web site led to the identification of 44 DRB, 33DQB, 29 DQA, 20 DPB, and 9 DPA unique combinations of polymorphic positions. The residue compositions of these patches were then determined from amino acid sequences. This analysis resulted in a repertoire of 146 DRB, 74 DQB, 58 DQA, 45 DPB, and 19 DPA eplets. In many eplets, the residues are in short linear sequences, but many other eplets have discontinuous sequences of residues that cluster on or near the molecular surface. This analysis has also shown that all serologically defined DR and DQ antigens detectable by monospecific antibodies have unique eplets. Other eplets are present in groups of class II antigens, many of which appear as cross-reacting. The eplet version of HLAMatchmaker should be considered as a hypothetical model for the structural assessment of donor-recipient compatibility and the determination of mismatch acceptability for sensitized patients. This computer algorith can be downloaded from the HLA Matchmaker Webside at http://tpis.upmc.edu.

HLA-DR Matching Improves Survival After Heart Transplantation: Is it Time to Change Allocation Policies?

HLA matching has improved outcome in kidney transplantation but is not considered in current allocation policies in heart transplantation. The aim of this single-center study was to assess the impact of HLA matching on long- term outcome after heart transplantation. The records of 240 consecutive heart transplant recipients (time period 1995 to 2002; mean age 51.8 +/- 11.7 years; mean follow-up 5.9 +/- 1.8 years) were analyzed retrospectively. According to the renal allocation policy, HLA mismatches (MM) on the major antigen loci HLA-A, HLA-B and HLA-DR were calculated, demonstrating 0 to 6 MM. Patients with primary graft failure were excluded from statistical analysis. Survival analysis revealed a statistically significant impact of HLA-DR MM on survival. Five-year survival was 90% in patients without HLA-DR MM (n = 10), 79% in patients with 1 HLA-DR MM (n = 113), and 68.1% in patients with 2 HLA-DR MM (n = 117) (1 MM vs 2 MM: p < 0.05). Freedom from cardiac allograft vasculopathy after 5 years was 89% in HLA-DR-identical recipients (n = 10), 61% in patients with 1 HLA-DR MM (n = 102), 54% in patients with 2 HLA-DR MM (n = 104). Conventional matching with 6 mismatches over the three major HLA antigen loci revealed a trend toward a higher relative risk for adverse outcome in patients with increased MM. HLA-DR matching had a significant impact on survival after heart transplantation (HTx) at our center. In the effort to achieve the best comparative use of scarce donor organs the inclusion of HLA-DR matching into allocation policies might improve long-term outcome after HTx.

Effect of human leucocyte antigen matching on the incidence of acute rejection in renal transplantation.

The influence of human leucocyte antigen (HLA) matching on the incidence of acute rejection and graft survival was examined in 181 consecutive patients receiving cadaveric renal transplants. Allografts with better HLA-DR and HLA-B matching showed significantly lower rejection rates than less well matched grafts on both univariate (rejection rates 25, 62 and 82 per cent for zero, one and two DR mismatches; P < 0.001) and multivariate analysis. Rejection episodes occurred earlier in mismatched grafts (P < 0.001). Superior matching was associated with improved graft function at 1 year after transplantation (mean serum creatinine level 137, 180 and 225 mumol l-1 for zero, one and two DR mismatches; P < 0.05). No association was, however, demonstrated between the degree of matching and overall graft survival. Good HLA matching reduces the number of acute rejection episodes, producing significant savings in drug costs and hospital stay. Long-term graft function is improved and minimizing early graft damage helps to avoid later development of chronic rejection.

Triple therapy in cadaver renal transplantation.

One hundred consecutive first (n = 72) and regrafted (n = 28) cadaver renal allograft recipients were immunosuppressed with cyclosporin, azathioprine and prednisolone (triple therapy) and followed for a median of 17.3 months (range, 7-26 months). Actuarial patient survival at 12 and 24 months was 97.7 per cent. Actuarial graft survival at 12 and 24 months was 79.5 per cent (first graft recipients 81.3 per cent and regrafted recipients 75 per cent). HLA-DR matching significantly improved graft survival which was 93 per cent at 1 year in patients given HLA-DR compatible kidneys, compared with 83 and 54 per cent, respectively, in patients who received kidneys mismatched for one or two HLA-DR antigens. There were 0.8 (s.d. = 0.7) episodes of acute rejection per patient during the first 3 months after transplantation. Triple therapy provides effective immunosuppression without evidence of over immunosuppression and reduces the incidence of cyclosporin side-effects. Although acute nephrotoxicity was uncommon, serum creatinine remained elevated 6 and 12 months after transplantation.

Banking on human embryonic stem cells: estimating the number of donor cell lines needed for HLA matching

Human embryonic stem (hES) cells are a promising source for transplantation to replace diseased or damaged tissue, but their differentiated progeny express human leucocyte antigens (HLAs) that will probably cause graft rejection. The creation of a bank of HLA-typed hES cells, from which a best match could be selected, would help reduce the likelihood of graft rejection. We investigated how many hES cell lines would be needed to make matching possible in most cases. The number of hES cell lines needed to achieve varying degrees of HLA match was estimated by use of, as a surrogate for hES-cell donor embryos, blood group and HLA types on a series of 10,000 consecutive UK cadaveric organ donors. The degree of blood group compatibility and HLA matching for a recipient population consisting of 6577 patients registered on the UK kidney transplant waiting list was determined, assuming all donor hES cell lines could provide a transplant for an unlimited number of recipients. A bank of 150 consecutive donors provided a full match at HLA-A, HLA-B, and HLA-DR for a minority of recipients (<20%); a beneficial match (defined as one HLA-A or one HLA-B mismatch only) or better for 37.9% (range 27.9-47.5); and an HLA-DR match or better for 84.9% (77.5-90.0). Extending the number of donors beyond 150 conferred only a very gradual incremental benefit with respect to HLA matching. A panel of only ten donors homozygous for common HLA types selected from 10,000 donors provided a complete HLA-A, HLA-B and HLA-DR match for 37.7% of recipients, and a beneficial match for 67.4%. Approximately 150 consecutive blood group compatible donors, 100 consecutive blood group O donors, or ten highly selected homozygous donors could provide the maximum practical benefit for HLA matching. The findings from these simulations have practical, political, and ethical implications for the establishment of hES-cell banks.

Impacts of donor and recipient's SNP of cytokine and cytokine receptor on early acute renal allograft rejection

To investigate the impact of donor and recipient's SNP of cytokine and cytokine receptor on early acute rejection after renal transplantation. (1) 129 cases of cadaveric renal allograft recipients were divided into two groups according to the presence or absence of acute graft rejection. The distribution of 21 single nucleotide polymorphisms in cytokines and cytokine receptors gene were compared between two groups as well as latent factors affecting the development of acute rejection. (2) Based on the result of HLA-DR matching between donor and recipient, the recipients with AR were stratified into two conditions, 0-1 locus mismatched (0-1MM) and completely mismatched (2MM). By aids of SPSS 11.5 software, association analysis was assessed using Kruskal Wallis test, 2 x 2 or 2 x n contingency table, the Chi-square test. (1) Of 129 recipients of renal transplantation, 39 developed acute graft rejection (30.2%). (2) Compared with recipients without acute rejection, the number of HLA-DR mismatching was significantly higher in rejection group. (3) In rejection group and non-rejection group, the gene polymorphism distribution was significantly different. (4) 0-1MM group and 2MM group were various in the gene polymorphism distribution. In the whole, the susceptibility of acute rejection after renal transplantation may be predicted by the donor and recipient's SNP of cytokine and cytokine receptor.