A novel DRB1*04 allele.

Discovery of the novel DRB1*0464 allele is described. This allele contains a nucleotide substitution in codon 13 that changes the amino acid histidine coded for in all other DRB1*04 alleles to tyrosine. This allele was found in a parent and one child of a North American Caucasian family with the haplotype: A*03, B*07, DRB1*0464, DRB4*0103, DQB1*0301.

Cytotoxic flow-cytometric crossmatches (flow-tox): a comparison with conventional cytotoxicity crossmatch techniques.

Detection and avoidance of donor-reactive antibodies in the sera of potential organ transplant recipients is key to a successful transplant outcome. Techniques of antibody detection that use flow cytometry are more sensitive than those that rely upon a visual determination of cytotoxicity. However, as conventionally performed, flow-cytometric crossmatches do not distinguish between cytotoxic (complement fixing) and noncytotoxic antibodies because both types of antibodies can bind to a cell and be detected by laser-activated fluorochrome photon emission. In 1989 we described two techniques for detecting cytotoxic antibodies using flow-cytometric techniques [1]. In 1990, we expanded the application of these new techniques that we called flow cytotoxicity assays or "Flow-Tox" [2]. Flow-Tox crossmatches demonstrate an increase in both sensitivity and specificity over conventional cytotoxicity crossmatches.

Outcome of renal transplantation at Oregon Health Sciences University: 1982 to 1990.

1. Graft survival increased over the 4 periods between 1982 and 1990 (82-84, 85-86, 87-88, 89-90). The largest increase was in the 89-90 period. 2. Immunosuppression was the key to improved outcome. Cadaveric graft recipients given OKT3 induction plus triple therapy with cyclosporine, azathioprine, and prednisone had significantly better graft survival compared with all other drug combinations. Other factors were improved patient selection, donor management, and outpatient care. 3. Mean serum creatinine levels did not change after cyclosporine was introduced for immunosuppression. The mean serum creatinine level was approximately 1.7 mg/dl at 3 months, 6 months, and 12 months post-transplantation in all 4 periods. 4. Living-related donor outcome was significantly better than cadaveric donor outcome. Half-life for 2-haplotype-matched kidneys was 37 years compared with 12 years for 1-haplotype matches and 6.5 years for cadaveric kidneys. 5. Immediate function and a rejection-free first month were both associated with significantly improved graft survival. 6. Neither peak PRA nor graft number (1st vs regraft) correlated with graft survival. Highly sensitized (PRA greater than 50%) patients and regrafted patients fared as well as less sensitized (PRA less than or equal to 50%) and first graft recipients. This outcome was attributed to a sensitive crossmatch. Because of the crossmatch, highly sensitized patients received much better HLA matches. 7. The incidence of early rejection and delayed function declined significantly between the earliest and latest periods. Improved immunosuppression, donor management, and renal preservation were cited as contributing factors.

Successful cadaver kidney transplantation in patients highly sensitized by blood transfusions. Unimportance of the most reactive serum in the pretransplant crossmatch.

Six patients who underwent a prospective blood transfusion protocol developed antibodies reactive with 41-95% of a lymphocyte panel. These antibodies disappeared 9-18 months later, and all six patients were successfully transplanted with cadaver kidneys in spite of positive crossmatches with donor T and B cells using their most reactive noncurrent sera. Crossmatches with their current sera were negative. No patient underwent plasmapheresis, blood transfusions, or immunosuppression between the time of maximum panel reactivity and transplantation. Graft survival was 100% after a mean of 22.3 months, and the mean serum creatinine level was 2.1 mg/dl one year after grafting. A positive anti-donor T or warm B cell crossmatch with the most reactive serum may be disregarded if the most recent serum is crossmatch-negative with a cadaver kidney transplant donor.