HLA-DR Compatibility Research Articles

Orchestrating the Impact of KIR/HLA Interactions on Kidney Transplant.

This study examines the interplay between human leukocyte antigen (HLA) compatibility and killer-cell immunoglobulin-like receptor (KIR) genotypes in influencing kidney transplantation outcomes. Understanding these interactions is crucial for improving graft survival and minimizing rejection risks. We evaluated 84 kidney transplant recipients, dividing them into two groups based on post-transplant outcomes: there were 68 with stable graft function (SGF) and 16 who experienced chronic rejection (CR). Patients were selected based on specific inclusion criteria. HLA mismatches (Class I: HLA-A, -B; Class II: HLA-DR) and KIR genotypes were determined using standard genotyping techniques. Statistical analyses, including logistic regression, were performed to correlate these factors with transplant outcomes. Significant age differences were observed, with younger patients more likely to experience graft rejection, while no significant gender-based differences were noted. A significant correlation was found between Class II mismatches and increased rejection rates, highlighting the importance of HLA-DR compatibility. Further analysis revealed that certain inhibitory KIRs, such as KIR3DL1, were associated with favorable outcomes, suggesting a protective role against graft rejection. These findings were corroborated by evaluating serum creatinine levels over multiple years, serving as a biomarker for renal function post transplant. This study underscores the critical need for meticulous HLA matching and the consideration of KIR genotypes in pre-transplant evaluations to enhance graft survival and minimize rejection risks. Integrating these genetic factors into routine clinical assessments could significantly improve personalized transplant medicine strategies, ultimately enhancing patient outcomes. Further research is needed to explore the underlying mechanisms and validate these findings in larger, diverse populations.

340.3: Comparison of HLA Compatibility Algorithms to Predict Longterm Survival and CLAD Following Lung Transplantation

Introduction: Outcomes following lung transplantation (LTx) remain poor, despite recent advances in sequencing technology and the development of multiple algorithms defining immunological compatibility between recipient and donor. No consensus has been achieved regarding the best approach to define HLA compatibility in LTx. Here, we compared numerous available HLA compatibility approaches, including T- and B-cell epitopes, electrostatic charge and amino acid mismatching, using a high resolution typed, well characterised cohort, to determine which approach best predicts outcomes following LTx. Methods: In this retrospective single-center study, 277 donor-recipient transplant pairs were retrospectively HLA typed by Next generation sequencing (NGS) for all HLA loci. (HLA-A-DPA). HLA mismatching was defined using HLAMatchmaker eplets (epMM), HLA-EMMA epitopes (EMMA), PIRCHE T-cell epitopes (PIRCHE), electrostatic differences (EMS) and amino Acid mismatches (AAMM). Associations with mismatching scores generated by the different algorithms with CLAD (BOS/RAS) and overall survival were calculated using adjusted cox proportional modelling and Kaplan-Meier survival curves to demonstrate time to outcomes (SPSS v.21). Results: Lower HLA-class II compatibility was associated with increased overall survival for all algorithms, with lower HLA-DR, -DQ and –DQA mismatches generated by PIRCHE and epMM independently associated with increased survival. Lower HLA-DR compatibility was significantly associated with increased time to RAS for all algorithms. Lower epMM and PIRCHE HLA-DQA was also associated with increased time to RAS, however the algorithms that did not separate DQA and DQB, did not reach significance. Conclusion: Lower class II mismatching, specifically for HLA-DR and DQ, for all approaches associated with improved graft and patient survival. The PIRCHE and HLAMatchmatcher algorithms that separate compatibility based on individual alleles/chains provide a higher degree of granularity, which may be useful to select the best matched recipient. Regardless, reducing the level of HLA mismatching, in either T- or B-cell epitopes, electrostatic differences or amino acid would improve outcomes following LTx and potentially guide immunosuppression strategies.

Reciprocal HLA-DR allogenicity between mother and child affects pregnancy outcome parameters

Successful pregnancy outcome depends on local immunoregulatory mechanisms preventing a detrimental immune response towards the semi-allogeneic fetus. We investigated the influence of HLA-DR (in)compatibility on pregnancy outcome parameters in 480 women. The parameters tested were birth weight, individualized birthweight ratio (IBR), gestational age, and maternal highest diastolic blood pressure. Irrespective of pregnancy complications, maternal-fetal HLA-DR incompatibility resulted in increased IBR. We conclude that reciprocal HLA-DR allogenicity between mother and child positively affect pregnancy outcome parameters.

Non–Heart-Beating Donor Kidney Transplantation Survival Is Similar to Donation After Brain Death: Comparative Study With Controls in a Regional Program

Non–heart-beating donors (NHBD) are an increasing source of organs for kidney transplantation (KT) compared with donation after brain death (DBD), but the results in each regional transplantation program require local analysis. We compared 164 KT from NHBD (83 Maastrich type II A-B [T2] and 81 type III [T3]) with 328 DBD controls. NHBD kidneys were implanted with less cold ischemia, mean time on renal replacement therapy for NHBD recipients before transplantation was less too, and a higher proportion of thymoglobulin was also used. Besides NHBD-T2 more frequently showing the A group and patients being younger (48.9 ± 11 vs DBD 55.2 ± 15 years old; P < .001), there was a lower proportion of retransplant recipients and HLA sensitization; HLA-DR compatibility was slightly worse. Proportion of nonfunctioning allograft and necessity of dialysis after transplantation for NHBD were 4.9 and 68.3% versus DBD 4.3 and 26.9% (P < .001); renal function after a year was significantly less in NHBD (serum creatinine 1.79 ± 0.9 mg/dL vs 1.46 ± 0.5 in DBD; P < .001). NHBD recipient survival rates were 96% and 96% for the 1st and 3rd years, respectively, versus 96% and 94% for DBD, respectively (not significant [NS]). Graft survival rates censored by death were 91% and 89% (1st and 3rd years, respectively) versus 95% and 94% for DBD, respectively (NS). We did not find significant differences about survival between NHBD-T2 and T3. In the multivariable survival study (Cox, covariables with statistical significance demonstrated previously in our region), NHBD is not a prognosis factor for recipient or graft survival. Regarding current criteria for choosing donors and the graft allocation applied in Andalusia, short-term survival for NHBD transplantation is similar to DBD. Renal function in the short term is slightly worse, which is why it is important to monitor results over a long term, especially those from NHBD-T2.

Survival of Kidney Allograft of Donors after Circulatory Death Is Similar to Donors after Brain Death: Experience in a Regional Program

BackgroundDonors after circulatory death (DCD) are an increasingly crucial source of organs to maintain deceased donor kidney transplant activity when faced with a standstill in donors after brain death (DBD). We analyzed the influence on graft survival since the use of DCD organs was implemented in Andalusia (2010–2014). MethodsWe compared 164 kidney transplants from DCD (83 Maastricht type II and 81 type III) and 1488 DBD transplants in recipients over the age of 18, excluding combined transplants. ResultsDCD were more frequently men from the A blood group who were younger (48.9 ± 11 vs 55.2 ± 15 years old for DBD, P < .001). Kidneys from DCD were implanted in younger recipients (51.2 ± 11 vs 53.5 ± 13 years old for DBD, P = .03), more frequently in men from blood group A who spent less time in renal replacement therapy (39.8 vs 51.5 months), in a lower proportion of immunized recipients and re-transplant patients, and had worse HLA-DR compatibility. DCD presented a proportion of primary nonfunctional allografts and an initial need for dialysis of 8.8% and 69.6% vs 5.5% and 29.6% for DBD (P < .001). DCD allograft recipient survival was 96% and 96% at the first and third year respectively, vs 96% and 93% with a DBD graft (NS). Survival of the graft was 91% and 86% at the 1st and 3rd years, vs 90% and 86% with a DBD allograft (NS). No significant difference was found between Maastricht type II and III. DCD were related to lower graft survival versus DBD under the age of 50 (n = 445), 86% vs 92% (P = .02) in the third year, but were similar to DBD from age 50 to 59 (n = 407) and higher than DBD over age 60 (n = 636), 80% at the 3rd year (NS). The survival of DCD recipients was not different than DBD in those under 60 and was significantly better than DBD at or over the age of 60 (96% vs 87% in the 3rd year, P = .036). In the multivariable survival study (Cox, covariates of influence previously demonstrated in our region) DCD are not a significant survival prognosis factor for the recipient or the allograft. ConclusionsWith the current guidelines of donor selection and allocation of organs applied in Andalusia, the survival of kidney transplants from DCD overall is similar to DBD. The graft performance tends to be better than DBD over the age of 60, the main source of donors at present.

A New HLA Allocation Procedure of Kidneys From Deceased Donors in the Current Era of Immunosuppression

IntroductionIt has recently been proposed to replace the current Eurotransplant kidney allocation based primarily on mismatches (MM) at the 3 HLA loci by a simpler system based on full HLA-DR compatibility. The present study analyzes this system in the current era of immunosuppression. MethodsFrom 1999 to 2012, 723 renal grafts were performed on 586 patients who were treated with a calcineurin inhibitor, mycophenolate mofetil, and in most cases antilymphocyte globulins. Four groups of HLA MM were compared: (A) A+B 2-4/DR 1-2 MM (n = 397), (B) A+B 2-4 MM/DR 0 MM (n = 106), (C) A+B 0-1 MM/DR 1-2 MM (n = 138), and (D) A+B 0-1/DR 0 MM (n = 82). ResultsAcute rejection episodes were less frequent during the first post-transplantation year in group D than in the other groups (P = .018). Patient survival was lower in group A than in the other groups (P = .008). Immunologic graft survival was higher in group D than in the other groups in univariate (P = .015) and multivariate analyses (P = .033; 96.4% vs 90.1% at 10 years). ConclusionsIn the current era of immunosuppression, allocation of kidneys from deceased donors could be performed primarily according to full DR compatibility then to the best A+B matching, affording excellent graft outcome to most recipients.

De Novo DQ Donor-Specific Antibodies Are Associated With a Significant Risk of Antibody-Mediated Rejection and Transplant Glomerulopathy

The importance of human leukocyte antigen (HLA) matching in renal transplantation is well recognized, with HLA-DR compatibility having the greatest influence. De novo DQ donor-specific antibodies (DSAbs) are the predominant HLA class II DSAb after transplantation. The aim of this study was to establish the incidence and outcomes after the development of DQ DSAbs along with the impact of class II HLA mismatch on their development. We retrospectively analyzed 505 patients who received a renal-alone transplant between 2005 and 2010. We excluded patients who received an ABO- and HLA-incompatible allograft, which we defined as those with a positive crossmatch or preformed DSAbs detected by single-antigen beads only. Of 505 patients, 92 (18.2%) developed DSAbs, with 50 (54.3%) of these 92 patients having DQ DSAbs. Patients who developed DQ DSAbs were at significant risk for antibody-mediated rejection, transplant glomerulopathy, and allograft loss (P<0.0001). Of 505 patients, 108 (21.4%) were matched at both the DR and DQ loci, 284 (56.2%) were mismatched at both loci, 38 (7.5%) were matched at DR alone, and 75 (14.9%) were matched at DQ alone. Patients mismatched at both DR and DQ were at risk for developing class II DSAbs when compared with those mismatched at either DR or DQ alone, P=0.001, and were at risk for antibody-mediated rejection, P=0.001. DQ DSAbs are associated with inferior allograft outcomes. This study shows the importance of establishing the DQ match before transplantation to define immunologic risk.

Regional Kidney Allocation Based Only on Full HLA-DR Compatibility Is Not Feasible

Regional Kidney Allocation Based Only on Full HLA-DR Compatibility Is Not Feasible

A study of HLA-G polymorphism and linkage disequilibrium in renal transplant patients and their donors

The role of the Major Histocompatibility Complex (MHC) in transplantation immunology is widely known. Incompatibilities associated with Human Leukocyte Antigens (HLA) between donors and recipients are related to poorer prognosis in allograft acceptance and survival, often resulting in rejection episodes. HLA-A, HLA-B, HLA-DR and HLA-DQ compatibility are widely studied in clinical transplants but few studies investigated the influence of non-classical HLA loci, such as HLA-G, a non-classical class I HLA gene located at 6p21.31 in the MHC region, i.e. 300 kb telomeric to HLA-A. MHC region genes are characterized by extreme polymorphism as well as strong positive linkage disequilibrium (LD) between HLA loci (alleles). LD studies related to MHC region provide investigators with a tool to assess candidate genes with an at-risk HLA haplotype, with implications for allograft transplants, human reproduction and disease susceptibility. Many studies reported striking LD between HLA-G and HLAA alleles and also between HLA-G and HLA Class II alleles, but the biologicalimplications for these findings are not clear yet. DNA sequencing methodology was used to determine HLA-G (exons 2 and 3) polymorphisms from 52 patients who underwent kidney transplantation and their donors. It is the purpose of this study to investigate the influence of HLA-G polymorphism in a set of kidney transplants and the occurrence of rejection episodes. It was observed that pairs with 2 HLA-G matches presented a lower risk of rejection occurrence than those pairs with 0 or 1 match. It was also observed that subjects whose genotype presented one synonymous substitution (S) in one HLA-G allele in the HLA-G⁎0101 group of alleles and another allele with a non-synonymous substitution (N/S) on HLA-G⁎0103, HLA-G⁎010401, HLA-G⁎010403 or HLA-G⁎0105N alleles, apparently had a greater chance of rejection episodes. Additionally, HLA-G, as well as HLA-A, -B e -DR, compatibility may also be important for allograft acceptance (rejection probability lower than 0.09%). Besides, heterozygous S/NS patients had a five times greater chance of rejection than S/S and NS/NS patients. Some haplotypes found in the present study were already described in literature: A⁎01-G⁎01B (⁎010102 or ⁎0106), A⁎03-G⁎0101A, A⁎23-G⁎010401, A⁎26-G⁎01B, A⁎31-G⁎0103, A⁎02-G⁎0101A, A⁎24-G⁎0101A, A⁎33-G⁎0103, A⁎68-G⁎01B. We have also described LD between HLA-G alleles and HLA class II DRB1⁎ allelic groups and found significant LD between DRB1⁎04-G⁎01B, DRB1⁎13-G⁎010401, DRB1⁎14-G⁎010108, DRB1⁎15-G⁎0103, DRB1⁎03-G⁎0101A and DRB1⁎03-G⁎01B.

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.

Simpler and Equitable Allocation of Kidneys From Postmortem Donors Primarily Based on Full HLA-DR Compatibility

The introduction of human leukocyte antigen (HLA)-matching in nonliving kidney transplantation has resulted into a better graft outcome, but also in an increase of waiting time, especially for patients with rare HLA phenotypes. We addressed the question of the differential influence of HLA-DR-matching versus HLA-A,B in clinical kidney transplantation. We used Kaplan-Meier product limit method to estimate survival rates, and Cox proportional hazard regression for the estimation of relative risks (Hazard-ratios) for different variables. A single center study (n=456 transplants, performed between 1985 and 1999) showed that full HLA-DR compatibility leads to a lower incidence of biopsy confirmed acute rejections in the first 180 posttransplantation days. These results were substantiated using the Eurotransplant database (n=39,205 transplants performed between 1985 and 2005) where graft survival in the full HLA-DR compatible group was significantly better than in the incompatible. An additional positive effect of HLA-A,B matching was only found in the full HLA-DR compatible group. In both studies, the introduction of a single HLA-DR incompatibility eliminates the HLA-A,B matching effect. We propose to allocate postmortem kidneys only to patients with full HLA-DR compatibility, and use HLA-A,B compatibility as an additional selection criterion. All patients, irrespective of their ethnic origin, will profit since the polymorphism of HLA-DR is by far lower than that of HLA-A,B. Excessive kidney travel and cold ischemia time will be significantly reduced.

THE ACCEPTABLE MISMATCH PROGRAM AS A FAST TOOL TO TRANSPLANT HIGHLY SENSITISED PATIENTS AWAITING A CADAVER KIDNEY: SHORT WAITING TIME AND EXCELLENT GRAFT OUTCOME.

O355 Aims: Transplantation of highly sensitised (HS) patients. Introduction: HS patients (≥85% PRA) accumulate on the waiting list of organ exchange organisations. Recently, several protocols have been developed to remove the donor-specific HLA antibodies from the serum of these patients before transplantation. These approaches including the use of intravenous immunoglobulins, plasmapheresis and immunoglobulins or immunoabsorption seem to lead to a certain success rate. In addition to the considerable financial burden, the additional immunosuppression needed may have an impact on the short term (infections) and long term (incidence of cancer) immune surveillance. Here, we advocate the selection of crossmatch negative donors on the basis of the Acceptable Mismatch (AM) Program as the first and best option to transplant HS-patients. The AM-Program was established about 20 years ago. It makes use of holes in the immune repertoire of the patients, which depends on the self-antigens and presumably also on those seen during the gestation period. Both historical and current immunisation of the patient is considered important. On the basis of extensive laboratory studies, those HLA antigens are defined towards which the patient never has formed antibodies. These antigens are considered to be acceptable as a mismatch in future kidney donors. Additional information is provided by Matchmaker, an algorithm based on the concept that immunogenic epitopes are represented by amino acid triplets on those parts of the HLA molecule accessible to alloantibodies, and those “self” triplets on the mismatches HLA-A or HLA-B molecules do not lead to alloimmune response. A negative crossmatch with blood-group compatible organ donors is predicted on the basis of compatibility of the donor HLA-A, B and DR antigens with the combination of the patient HLA-A, B, DR antigens and the AM. Minimal matching criteria of one HLA-B and one HLA-DR sharing or full HLA-DR compatibility are required. The organ exchange is mandatory. Results: The waiting list for the AM-patients comprises currently 163 patients. In the period 01.01.2002 – 30.06.2003, 129 patients entered the AM-program. In the same period of time 68 patients were transplanted. Fifty-seven patients (mean waiting time 9.7 months, range 0-130 months) received the offer directly via the AM and 11 patients (mean waiting time 18.6 months, range 1-96 months) via the ET-KAS. The majority of the patients transplanted via the AM received the offer within the first 6 months after entering the program. The graft survival of AM (87% at 2 years) is identical to the group of the unsensitized patients in ET. Factors, such as matching, and historical vs. current sensitisation did not alter the results. Conclusions: Highly sensitised patients profit from the AM program. As the nature of the HLA polymorphism does not allow all patients to profit from this approach removal of circulating HLA antibodies can be considered as a rescue therapy for those patients for whom the AM-program does not give a solution.

Hlamatchmaker-based determination of HLA-DR and HLA-DQ compatibility at the structural level

Hlamatchmaker-based determination of HLA-DR and HLA-DQ compatibility at the structural level

Matching for HLA in cadaveric renal transplantation revisited: major impact of the full HLA-DR compatibility allowing simpler and equitable allocation of organs

Matching for HLA in cadaveric renal transplantation revisited: major impact of the full HLA-DR compatibility allowing simpler and equitable allocation of organs

Immunologic monitoring of the beneficial effect of one HLA-DR-shared blood transfusion in heart transplant patients

Background: Pre-transplant blood transfusion (BT) results in better graft survival in organ transplant recipients, especially when BT donor and allograft recipient share an HLA-DR antigen. Although the immunologic mechanisms involved are still poorly understood, we wanted to know whether down regulation of donor-reactive T cells play a role. Methods In a retrospective study, we analyzed the clinical effects of BT for 45 heart transplant (HTx) patients who had each received 1 BT that shared an HLA-DR-antigen with the recipient, and 55 who had a DR-mismatched BT before heart transplantation. From 30 patients, 15 with DR-shared BT and 15 with DR-mismatched BT, peripheral blood lymphocytes (PBL) were available. From each patient, we analyzed PBL samples taken at the day of transplantation (pre-transplant), and 1 to 2 months, 5 to 7 months, 9 to 14 months, 2 years, and 6 to 7 years after transplantation. Cytotoxic T-lymphocyte precursors (CTLp) and helper T-lymphocyte precursors (HTLp) were measured in a combined limiting dilution assay. Results Analysis of survival during the first 10 years revealed a significantly ( p = 0.016) better survival rate in the group of patients who had received HLA-DR–shared BT compared with the group who had received HLA-DR–mismatched BT. Patients of the DR-shared group experienced significantly ( p = 0.042) less acute rejections compared with the patients who received DR-mismatched BT. We found no differences in the development of graft vascular disease. Frequencies of CTLp specific for the organ donor did not change with time after transplantation in the individual patients, nor did we detect any differences between the two BT groups. We found the same for organ donor–specific HTLp frequencies. Conclusions These data suggest again that transfusion effect depends on HLA-DR compatibility between the heart transplant recipient and the pre-transplant BT donor. The mechanism that caused better survival rate was not down regulation of the donor-reactive T-cell frequency.

Increased HLA-DR homozygosity associated with pre-eclampsia

It is generally accepted that maternal recognition of paternally derived fetal antigens occurs during normal pregnancy and may be beneficial for implantation and maintenance of gestation. Thus, we have investigated the human leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with pre-eclampsia, their partners and in control couples. The HLA-DR antigens were tested in 70 pre-eclamptic primigravidae women and their partners and 70 healthy control couples using the serological Terasaki technique. Our results did not show any particular HLA-DR antigen to be correlated with pre-eclampsia, but a statistically significant increase of only one identifiable HLA-DR antigen, which was presumed to express homozygosity at the HLA-DR locus, in the pre-eclamptic women and their partners: 67.1 versus 7. 9% in the control couples (P < 0.000001). The analysis of HLA-DR compatibility between pre-eclamptic women and their partners showed a statistically highly significant increase of the female-to-male compatibility (P = 0.0003) and a lower but significant male-to-female compatibility in comparison with controls (P = 0.014). From our results, it emerges that HLA-DR homozygosity and reduced antigenic disparity seem to be associated to a major risk for pre-eclampsia, which consequently appears to be a 'couple's disease'.

HLA-DRB1 compatibility in cadaver kidney transplantation: correlation with graft survival and function.

The introduction of genomic HLA-DR typing has stimulated a re-evaluation of the role of HLA-DR compatibility on cadaver kidney transplantation. We retrospectively studied the influence of HLA-DRB1 matching on the survival of 416 patients using univariate and Cox regression analysis as well as its influence on the occurrence of rejection episodes and on creatinine level at the 3rd month in the 198 recipients for whom these data were available. The following parameters were also considered: HLA-A,B compatibility, donor and recipient age, graft number, pre-transplant blood transfusions and panel reactive antibodies (PRA). Twenty-four month graft survival was 100% for transplants with zero mismatches (n = 47), 87.9% for those with one mismatch (n = 191) and 81.3% for those with two mismatches (n = 178). In the Cox model, HLA-DRB1 matching was the most significant variable influencing graft survival (47% of chi 2 P = 0.001), followed by HLA-A,B matching (23%, P = 0.02) and donor age (19%, P = 0.04). Ninety-two percent of the patients with zero mismatches experienced no rejection episodes in the first 3 posttransplant months compared with 62% and 41% of patients with one and two mismatches, respectively. Mean creatinine level (mg/dl) was 1.2, 1.4, and 1.5 in patients with zero, one, and two mismatches, respectively. Should these results be confirmed by prospective studies, HLA-DRB1 compatibility will have to be considered as an organ allocation criterion.

Effect of HLA-DR compatibility between blood donor and recipient on clinical graft outcome

Effect of HLA-DR compatibility between blood donor and recipient on clinical graft outcome

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 typing: an important step forward?

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.