Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants.

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement-dependent cytotoxicity crossmatch (CDCXM) for the detection of anti-donor antibodies, that mediate hyperacute rejection and graft loss in the early post-transplant period in renal transplant recipients. The role of FCXM in predicting long-term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long-term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n = 100) with peak panel reactive antibody (PRA) levels > 30%, who received cadaveric renal transplants between 1/1/'90 and 12/31/'95 at our institution, were divided into FCXM + and FCXM - groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM + patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM + patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM - patients. There was no statistically significant difference in 1-, 2-, or 3-yr graft survival between FCXM + and FCXM - patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM + cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long-term allograft survival, FCXM may be a useful predictor of long-term clinical outcome in this sub-group of renal transplant recipients.

The genetic basis of alopecia areata: HLA associations with patchy alopecia areata versus alopecia totalis and alopecia universalis.

Many diseases, notably those having a strong autoimmune component, have been shown to have an association with specific human leukocyte antigens (HLA). The molecular basis for this genetic association with disease is the fact that HLA bind and present peptides derived from self and foreign protein antigens to the immune system for recognition and activation of the immune response. Previous studies with heterogeneous groups of alopecia areata (AA) patients have suggested associations with some HLA class I and class II antigens. For this study we selected only patients with long-standing disease and stratified them into two groups by strict definitions of duration and extent of disease: those with patchy AA and those with either alopecia totalis (AT) or alopecia universalis (AU). The patients were tissue typed for HLA class II antigens by biomolecular methods that provided antigen discrimination at an allele level. More than 80% of all of the AA patients typed were positive for the antigen DQB1*03 (DQ3), suggesting that this antigen is a marker for general susceptibility to AA. In addition, two other antigens were found significantly increased in frequency only in the group of AT/AU patients, DRB1*0401 (DR4) and DQB1*0301(DQ7). This strongly suggests that the two clinical types of AA, namely patchy AA versus AT/AU, can be distinguished by a genetically based predisposition to extent of disease.

An analysis of discrepancies in HLA phenotypes of cadaver donors in the united network for organ sharing registry.

BACKGROUND: HLA matching is an important component of the United Network for Organ Sharing algorithm for kidney allocation and is the primary factor in the mandatory sharing of kidneys that have zero HLA antigens mismatched with specific patients on the waiting list. An assessment of the HLA-A, -B, and -DR antigen discrepancy rate in the Organ Procurement and Transplantation Network database is desirable to judge the adequacy of the HLA typing data upon which the allocation program is based. METHODS: A subset of the Organ Procurement and Transplantation Network database, composed of 10,047 cadaver donor HLA phenotypes that have been repeated by laboratories affiliated with organ recipient centers, was analyzed for the overall rate of HLA phenotype discrepancy and for the type and frequency of discrepancies of the individual HLA antigen assignments. The United Network for Organ Sharing HLA antigen equivalences were applied to the data. RESULTS: Fourteen percent of 12,419 HLA typing comparisons were discrepant in at least one HLA antigen of six possible antigens per phenotype. Of a possible 74,514 individual HLA antigen assignments, 2.7% were discrepant. For African-American donors, the discrepancy rate was 5.1% as compared with 2.4% for Caucasian donors. The most frequent type of discrepancy was the assignment of an antigen blank versus a named antigen. CONCLUSIONS: The discrepancy rate is comparatively low and can be expected to improve as more laboratories adopt methods for HLA typing by DNA typing techniques. It is recommended that the HLA data be further reviewed by the laboratories for possible typographical errors and that centers review the UNOS listing of HLA antigen equivalences and encourage laboratories to split HLA antigens.

HLA class II antigen associations help to define two types of alopecia areata.

BACKGROUND: Multiple HLA class I and class II antigen associations have been described for alopecia areata (AA). As in other immune-mediated diseases, the HLA antigens associated with AA could influence the patient's ability to respond to immune challenge from both self- and non-self-antigens and may offer clues to the cause and prognosis of and potential therapy for the disease. OBJECTIVE: Our purpose was to determine which HLA class II antigens are associated with two forms of long-standing AA, which we define to be long-standing patchy AA and long-standing alopecia totalis (AT) and alopecia universalis (AU). We also examined other factors such as age at onset of disease and familial and patient histories of autoimmune disease for correlation with the two groupings. METHODS: Patients were typed for HLA class I and class II antigens by serologic methods and were typed by molecular methods for the subtypes of the HLA class II antigens. RESULTS: HLA-DR11 (DRB1*1104) and HLA-DQ7 (DQB1*0301) were found to be highly significantly increased in frequency in patients with long-standing AT/AU (group III) but not in patients with long-standing patchy AA (group II); both patient groups showed increased frequencies of HLA-DQ3 (DQB1*03). Group III patients were unique in their early age at onset of disease. Familial incidence of AA was 37% in patients who had their first patch by 30 years of age and 7.1% with the first patch after 30 years of age. CONCLUSION: The data support the differential association of two well-defined clinical forms of AA, namely long-standing AT/AU and long-standing patchy AA, with specific HLA antigens and age at onset; they also suggest that the broad antigen HLA-DQ3, DQB1*03, is a likely candidate for general susceptibility to AA. Our findings also suggest a bimodal pattern of disease with an early-onset form associated with greater severity, long duration, and family history of the disease and a late-onset form characterized by milder severity, shorter duration, and low family incidence.

Two patterns of sensitization demonstrated by recipients of donor-specific transfusion. Limitations to control by Imuran.

Characteristics of the sensitization response to donor-specific transfusion (DST) have been studied in the context of the pretransfusion panel reactive antibody (PRA) status of the recipient. Two distinct patterns of response to DST and Imuran treatment have been found. In patients with one-haplotype-matched donors, the panel nonreactive patient (PRA less than 10%) has a 19% incidence of DST sensitization that is further reduced by Imuran treatment to 6%; antibodies are both anti-T cell and anti-B cells, are transient, and are specific to the mismatched HLA antigens of the blood donor. Panel-reactive patients (PRA greater than 10%) have a 56% incidence of DST sensitization; the antibodies appear within 2 weeks of the first transfusion, are anti-T cell, and are generally of broad specificity and persistent duration consistent with amplification of a previous antigenic exposure; Imuran seems to have little or no effect in reducing the incidence of sensitization in these panel-reactive patients. However, panel reactive patients whose PRA levels spontaneously fall to panel-nonreactive levels immediately prior to DST therapy have an exceedingly low (0-8%) incidence of sensitization with or without Imuran coverage.