Link to the University of Pittsburgh Homepage
Link to the University Library System Homepage Link to the Contact Us Form

Multiscreen serum analysis of highly sensitized renal dialysis patients for antibodies toward public and private class I HLA determinants: Implications for computer-predicted acceptable and unacceptable donor mismatches in kidney transplantation

Duquesnoy, RJ and White, LT and Fierst, JW and Vanek, M and Banner, BF and Iwaki, Y and Starzl, TE (1990) Multiscreen serum analysis of highly sensitized renal dialysis patients for antibodies toward public and private class I HLA determinants: Implications for computer-predicted acceptable and unacceptable donor mismatches in kidney transplantation. Transplantation, 50 (3). 427 - 437. ISSN 0041-1337

[img]
Preview
PDF
Accepted Version
Available under License : See the attached license file.

Download (1MB) | Preview
[img] Plain Text (licence)
Available under License : See the attached license file.

Download (1kB)

Abstract

A multiscreen serum analysis program has been developed that permits a determination of antibody specificity for the vast majority of highly sensitized patients awaiting transplantation. This program is based on a 2 x 2 table analysis of correlations between serum reactivity with an HLA-typed cell panel and incorporates two modifications. One implements the concept of public HLA determinants based on the serologic crossreactivity among class I HLA antigens. The other modification derives from the premise that most highly sensitized patients maintain the same PRA and antibody profiles over many months and even years. Monthly screening results for patients with persistent PRA values can therefore be combined for analysis. For 132 of 150 highly sensitized patients with > 50% PRA, this multiscreen serum analysis program yielded information about antibody specificity toward public and private class IHLA determinants. The vast majority of patients (108 of 112) with PRA values between 50 and 89% showed antibody specificity generally toward one, two, or three public markers and/or the more common private HLA-A, B antigens. For 24 of 38 patients with > 90% PRA, it was possible to define one or few HLA-specific antibodies. The primary objective of the multiscreen program was to develop an algorithm about computer-predicted acceptable and unacceptable donor HLA-A, B antigens for patients with preformed antibodies. A retrospective analysis of kidney transplants into 89 highly sensitized patients has demonstrated that allografts with unacceptable HLA-A, B mismatches had significantly lower actuarial survival rates than those with acceptable mismatches (P = 0.01). This was shown for both groups of 32 primary transplants (44% vs. 67% after 1 year) and 60 retransplants (50% vs. 68%). Also, serum creatinine levels were significantly higher in patients with unacceptable class I mismatches (3.0 vs. 8.4 mg% [P = 0.007] after 2 weeks; 3.9 vs. 9.1 mg% [P = 0.014] after 4 weeks). Histopathologic analysis of allograft tissue specimens from 47 transplant recipients revealed a significantly higher incidence of humoral rejection (P = 0.02), but not cellular rejection, in the unacceptable mismatch group. These results suggest that the multiscreen program can establish which donor HLA-A, B mismatches must be avoided in kidney transplantation for most highly sensitized patients. For 18 of 150 high PRA renal dialysis patients, the multiscreen program could not define HLA-specific antibody. Most patients had > 90% PRA, and many of their sera appeared to contain IgM type nonspecific lympho- cytotoxins that could be inactivated by dithioerythreitol (DTE). Preliminary studies have shown that this treatment enabled the detection of HLA-specific antibodies upon subsequent screening on many occasions. These data suggest that non-HLA specific reactivity revealed by multiscreen analysis can often be removed by DTE treatment. Multiscreen analysis offers an attractive approach to regional organ-sharing programs for highly sensitized renal transplant candidates. It enables the development of an efficient strategy for donor selection based on the computer assignment of acceptable HLA-A, B mismatches for each patient. © 1990 by Williams and Wilkins.


Share

Citation/Export:
Social Networking:
Share |

Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Duquesnoy, RJ
White, LT
Fierst, JW
Vanek, M
Banner, BF
Iwaki, Y
Starzl, TEtes11@pitt.eduTES11
Centers: Other Centers, Institutes, or Units > Thomas E. Starzl Transplantation Institute
Date: 1 January 1990
Date Type: Publication
Journal or Publication Title: Transplantation
Volume: 50
Number: 3
Page Range: 427 - 437
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 0041-1337
Other ID: uls-drl:31735062116870, Starzl CV No. 1134
Date Deposited: 08 Apr 2010 17:19
Last Modified: 13 Oct 2017 21:56
URI: http://d-scholarship.pitt.edu/id/eprint/4520

Metrics

Monthly Views for the past 3 years

Plum Analytics


Actions (login required)

View Item View Item