Institutional Affiliations Chair Costanzo MR: Midwest Heart Foundation, Lombard Illinois, USA Task Force 1 Dipchand A: Hospital for Sick Children, Toronto Ontario, Canada; Starling R: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Anderson A: University of Chicago, Chicago, Illinois, USA; Chan M: University of Alberta, Edmonton, Alberta, Canada; Desai S: Inova Fairfax Hospital, Fairfax, Virginia, USA; Fedson S: University of Chicago, Chicago, Illinois, USA; Fisher P: Ochsner Clinic, New Orleans, Louisiana, USA; Gonzales-Stawinski G: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Martinelli L: Ospedale Niguarda, Milano, Italy; McGiffin D: University of Alabama, Birmingham, Alabama, USA; Parisi F: Ospedale Pediatrico Bambino Gesu, Rome, Italy; Smith J: Freeman Hospital, Newcastle upon Tyne, UK Task Force 2 Taylor D: Cleveland Clinic Foundation, Cleveland, Ohio, USA; Meiser B: University of Munich/Grosshaden, Munich, Germany; Baran D: Newark Beth Israel Medical Center, Newark, New Jersey, USA; Carboni M: Duke University Medical Center, Durham, North Carolina, USA; Dengler T: University of Hidelberg, Heidelberg, Germany; Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, USA; Frigerio M: Ospedale Niguarda, Milano, Italy; Kfoury A: Intermountain Medical Center, Murray, Utah, USA; Kim D: University of Alberta, Edmonton, Alberta, Canada; Kobashigawa J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Shullo M: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Stehlik J: University of Utah, Salt Lake City, Utah, USA; Teuteberg J: University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Uber P: University of Maryland, Baltimore, Maryland, USA; Zuckermann A: University of Vienna, Vienna, Austria. Task Force 3 Hunt S: Stanford University, Palo Alto, California, USA; Burch M: Great Ormond Street Hospital, London, UK; Bhat G: Advocate Christ Medical Center, Oak Lawn, Illinois, USA; Canter C: St. Louis Children Hospital, St. Louis, Missouri, USA; Chinnock R: Loma Linda University Children's Hospital, Loma Linda, California, USA; Crespo-Leiro M: Hospital Universitario A Coruna, La Coruna, Spain; Delgado R: Texas Heart Institute, Houston, Texas, USA; Dobbels F: Katholieke Universiteit Leuven, Leuven, Belgium; Grady K: Northwestern University, Chicago, Illlinois, USA; Kao W: University of Wisconsin, Madison Wisconsin, USA; Lamour J: Montefiore Medical Center, New York, New York, USA; Parry G: Freeman Hospital, Newcastle upon Tyne, UK; Patel J: Cedar-Sinai Heart Institute, Los Angeles, California, USA; Pini D: Istituto Clinico Humanitas, Rozzano, Italy; Pinney S: Mount Sinai Medical Center, New York, New York, USA; Towbin J: Cincinnati Children's Hospital, Cincinnati, Ohio, USA; Wolfel G: University of Colorado, Denver, Colorado, USA Independent Reviewers Delgado D: University of Toronto, Toronto, Ontario, Canada; Eisen H: Drexler University College of Medicine, Philadelphia, Pennsylvania, USA; Goldberg L: University of Pennsylvania, Philadelphia, Pennsylvania, USA; Hosenpud J: Mayo Clinic, Jacksonville, Florida, USA; Johnson M: University of Wisconsin, Madison, Wisconsin, USA; Keogh A: St Vincent Hospital, Sidney, New South Wales, Australia; Lewis C: Papworth Hospital Cambridge, UK; O'Connell J: St. Joseph Hospital, Atlanta, Georgia, USA; Rogers J: Duke University Medical Center, Durham, North Carolina, USA; Ross H: University of Toronto, Toronto, Ontario, Canada; Russell S: Johns Hopkins Hospital, Baltimore, Maryland, USA; Vanhaecke J: University Hospital Gasthuisberg, Leuven, Belgium.

http://www.jsht.jp/uploads/ISHLT_GL_TaskForce2_110810.pdf

The International Society of Heart and Lung Transplantation Guidelines for the care of heart transplant recipients

The microdroplet lymphocyte cytotoxicity test is universally accepted as the standard test for HLA antigen determination. An update of the technical details of the test is given, based on the authors’ testing 160,000 persons. Methods for quality control of the test as well as reproducibility data are provided. International standardization of the specificities has been accomplished by seven international workshops and a continuous cell exchange involving testing of 108 cells since 1974 by as many as 180 laboratories. The test has recently become applicable to the detection of HLA-D determinants, previously thought to be detectable only by lymphocyte-determined (LD) tests. Purified peripheral blood lymphocytes are reacted with antisera from which HLA-A, -B, and -C antibodies have been removed. B lymphocytes were found to be smaller than T lymphocytes by Coulter counter sizing. The purity of cell suspensions enriched for B lymphocytes can be individually monitored, as shown by the reactions produced by 126 test samples. HLA-D antigens have a linkage disequilibrium with certain HLA-A and -B specificities as demonstrated by population and family studies. Haplotypes found in 34 parents of 18 families demonstrate the new haplotypes, which now consist of four antigens per haplotype. Studies of HLA-D frequencies in Caucasians, Negroes, and Orientals show a distinctive distribution in the races. B lymphocytes also appear to have an autoantigen against which autoantibodies are readily produced. The autoantibodies are more active against B than T lymphocytes and act most effectively at 5 C. Although they appear in many diseases, most notably in systemic lupus erythematosus, they also occur in 10% of normal males and females. In patients awaiting kidney transplants, antibodies against B lymphocytes are often found. Patients with cold B-cell antibodies (autoantibodies) were shown to have higher transplant survival rates than those with warm B-cell antibodies (allogeneic). Thus, in performing crossmatch tests it is now necessary to distinguish antibodies against T and B lymphocytes and those that react in cold and in warm conditions.

Microdroplet testing for HLA-A, -B, -C, and -D antigens. The Phillip Levine Award Lecture.

http://cybernephrology.ualberta.ca/Banff/2015/Publications/banff09.pdf

Banff '09 meeting report: Antibody mediated graft deterioration and implementation of Banff working groups

The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non–complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific antiHLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donorspecific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). Conclusions Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.

/pdf/complement-binding-anti-hla-antibodies-and-kidney-allograft-3hvjdyrbqz.pdf

Complement-Binding Anti-HLA Antibodies and Kidney-Allograft Survival

The clinical importance of preexisting HLA antibodies at the time of transplantation, identified by contemporary techniques, is not well understood. We conducted an observational study analyzing the association between preexisting donor-specific HLA antibodies (HLA-DSA) and incidence of acute antibody-mediated rejection (AMR) and survival of patients and grafts among 402 consecutive deceased-donor kidney transplant recipients. We detected HLA-DSA using Luminex single-antigen assays on the peak reactive and current sera. All patients had a negative lymphocytotoxic cross-match test on the day of transplantation. We found that 8-year graft survival was significantly worse (61%) among patients with preexisting HLA-DSA compared with both sensitized patients without HLA-DSA (93%) and nonsensitized patients (84%). Peak HLA-DSA Luminex mean fluorescence intensity (MFI) predicted AMR better than current HLA-DSA MFI (P = 0.028). As MFI of the highest ranked HLA-DSA detected on peak serum increased, graft survival decreased and the relative risk for AMR increased: Patients with MFI >6000 had >100-fold higher risk for AMR than patients with MFI <465 (relative risk 113; 95% confidence interval 31 to 414). The presence of HLA-DSA did not associate with patient survival. In conclusion, the risk for both AMR and graft loss directly correlates with peak HLA-DSA strength. Quantification of HLA antibodies allows stratification of immunologic risk, which should help guide selection of acceptable grafts for sensitized patients.

Preexisting Donor-Specific HLA Antibodies Predict Outcome in Kidney Transplantation

Crossmatch tests of the prospective kidney-transplant donor's lymphocytes with the serum of the prospective recipient in 225 transplants showed that eight of 195 with negative crossmatch f...

Significance of the positive crossmatch test in kidney transplantation.

During the past four years 104 patients who had received kidneys from either living unrelated or cadaver donors were typed and analyzed, to assess the effect of matching on endogenous crea...

https://www.nejm.org/doi/pdf/10.1056/NEJM196809052791001?listPDF=true

Serotyping for Homotransplantation

The HL-A2 leucocyte antigen was found to be present in a significantly higher percentage of 485 patients with chronic glomerulonephritis than in 428 normal control subjects. No correlation could be shown between any of the ABO groups and chronic glomerulonephritis. There was no statistically significant difference in the frequency of HL-A2 when the controls were compared with 280 patients with a variety of other diseases. The trend toward an excess of HL-A2 positives among patients with glomerulonephritis was also seen in a study of 108 sibships, though the difference fell short of statistical significance. It was concluded that an HL-A2 positive person was about 1·5 times as likely to develop chronic glomerulonephritis as an HL-A2 negative person.

/pdf/leucocyte-antigens-and-disease-1-association-of-hl-a2-and-gs8j07o678.pdf

Leucocyte Antigens and Disease: 1. Association of HL-A2 and Chronic Glomerulonephritis

Serotyping for homotransplantation. XX. Selection of recipients for cadaver donor transplants.

During the first 11 months of an interhospital program of cadaver-kidney sharing and tissue typing, 77 possible donors were typed, and 47 kidneys from 30 donors were transplanted into 46 recipients. Sixteen transplants were compatible with respect to the five leukocyte antigens considered. There was a tendency to accumulate recipients with few or rare antigens who were difficult to match. When the effect of recipient-pool size was studied under a hypothetical situation, 80% of potential transplants were compatible if both donor kidneys were transplanted into two recipients selected from the pool of eight hospitals, whereas only 25% were compatible if the recipients were selected from the "donor" hospital alone. Interhospital cooperation could allow a maximum utilization of cadaver kidneys and rapidly provide data for a critical evaluation of tissue typing in cadaver-organ transplantation.

Ramon Patel

Papers

Significance of the positive crossmatch test in kidney transplantation.

Serotyping for Homotransplantation

Leucocyte Antigens and Disease: 1. Association of HL-A2 and Chronic Glomerulonephritis

Serotyping for homotransplantation. XX. Selection of recipients for cadaver donor transplants.

Serotyping for homotransplantation. XIX. Experience with an interhospital scheme of cadaver-kidney sharing and tissue typing.