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. 2006 Dec 20;1(1):e42.
doi: 10.1371/journal.pone.0000042.

V体育官网 - A uniform genomic minor histocompatibility antigen typing methodology and database designed to facilitate clinical applications

Eric Spierings  1 , Jos Drabbels, Matthijs Hendriks, Jos Pool, Marijke Spruyt-Gerritse, Frans Claas, Els Goulmy
Affiliations

A uniform genomic minor histocompatibility antigen typing methodology and database designed to facilitate clinical applications

Eric Spierings et al. PLoS One. .

Abstract

Background: Minor Histocompatibility (H) antigen mismatches significantly influence the outcome of HLA-matched allogeneic stem cell transplantation. The molecular identification of human H antigens is increasing rapidly VSports手机版. In parallel, clinical application of minor H antigen typing has gained interest. So far, relevant and simple tools to analyze the minor H antigens in a quick and reliable way are lacking. .

Methodology and findings: We developed a uniform PCR with sequence-specific primers (PCR-SSP) for 10 different autosomal minor H antigens and H-Y V体育安卓版. This genomic minor H antigen typing methodology allows easy incorporation in the routine HLA typing procedures. DNA from previously typed EBV-LCL was used to validate the methodology. To facilitate easy interpretation for clinical purposes, a minor H database named dbMinor (http://www. lumc. nl/dbminor) was developed. Input of the minor H antigen typing results subsequently provides all relevant information for a given patient/donor pair and additional information on the putative graft-versus-host, graft-versus-tumor and host-versus-graft reactivities. .

Significance: A simple, uniform and rapid methodology was developed enabling determination of minor H antigen genotypes of all currently identified minor H antigens. A dbMinor database was developed to interpret the genomic typing for its potential clinical relevance. The combination of the minor H antigen genomic typing methodology with the online dbMinor database and applications facilitates the clinical application of minor H antigens anti-tumor targets after stem cell transplantation. V体育ios版.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

"V体育官网入口" Figures

Figure 1
Figure 1. Minor H antigen PCR-SSP.
PCR-SSP of DNA of two unrelated individuals (CAN and 80821) was performed and analyzed as described in the Materials and Methods section. The first lane of each minor H locus represents the immunogenic allele; the second lane displays the non-immunogenic allele. Bands relevant for minor H antigen typing are boxed. The products of 439 and 504 bp reflect the internal control for the immunogenic and the non-immunogenic allele respectively. The control band for UGT2B17 has a size of 761 bp. Since the minor H antigens UGT2B17 and H-Y have no allelic counterpart, the latter typing was performed with a single set of primers.
Figure 2
Figure 2. Structure of the minor H antigen database (dbMinor).
Data from dbMinor are obtained via direct submission and from literature screening. The data in dbMinor can be analyzed via an HLA-based query, a full typing query and a minor H antigen query. Results from these queries are linked to external data from the NCBI database.
Figure 3
Figure 3. Analysis of donor/recipient HLA and minor H antigen typing.
A. Query section: Minor H antigen typing data can be entered by marking the checkboxes per allele per minor H antigen. HLA typing data has the 2-digit format. Full typing for all HLA loci is not required. After submitting the query, a page with results will appear B. Results: The results section lists minor H antigens relevant in the particular donor-recipient combination based upon the HLA typing. In case donor and recipient are minor H antigen matched, as is the case here for HA-1, the sign “ = ” will appear between donor and recipient. In case recipient and donor are minor H antigen mismatched, the disparities are indicated by an arrow. The direction of the arrow indicates the direction of the immune responses. In this example immune reactivity can occur in the recipient-to-donor (host-versus-graft, rejection) direction for HA-2 and HA-3 and in the donor-to-recipient (graft-versus-host) direction for HA-8 and for the various H-Y antigens. The tissue distribution of each relevant minor H antigen is listed as “broad” or “restricted”. By clicking these terms, a detailed list of target cells expressing the minor H antigen will be displayed. Minor H antigens are presented by selected HLA molecules. The HLA alleles expressed by recipient and donor that are not able to present a minor H antigen are listed at the bottom of the results section. Information will appear in case a particular minor H antigen cannot be presented by a specific HLA sub-allele (4-digit format; in this example HLA- DQB1*0503/0504 for DQ5/H-Y).
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References

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