Analysis of donor/recipient HLA and minor H antigen typing.

<div><p>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</p> <p>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.</p> <p>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.</p> <p>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).</p></div

Minor H antigen PCR-SSP.

<div><p>PCR-SSP of DNA of two unrelated individuals (CAN and 80821) was performed and analyzed as described in the Materials and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0000042#s3" target="_blank">Methods</a> section.</p> <p>The first lane of each minor H locus represents the immunogenic allele; the second lane displays the non-immunogenic allele.</p> <p>Bands relevant for minor H antigen typing are boxed.</p> <p>The products of 439 and 504 bp reflect the internal control for the immunogenic and the non-immunogenic allele respectively.</p> <p>The control band for UGT2B17 has a size of 761 bp.</p> <p>Since the minor H antigens UGT2B17 and H-Y have no allelic counterpart, the latter typing was performed with a single set of primers.</p></div

Structure of the minor H antigen database (dbMinor).

<div><p>Data from dbMinor are obtained via direct submission and from literature screening.</p> <p>The data in dbMinor can be analyzed via an HLA-based query, a full typing query and a minor H antigen query.</p> <p>Results from these queries are linked to external data from the NCBI database.</p></div

Table_1.PDF

<p>Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.</p