Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti‐HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy‐five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post‐LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence‐based typing and Luminex sequence‐specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA‐DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71–8.29 p < 0.001). When bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS) were analyzed independently, HLA‐DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46–27.97 p < 0.001) but not BOS (HR 1.92, 95% CI: 0.64–5.72, p = 0.237). HLA‐A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor–recipient immune compatibility in LTx.

Methotrexate (MTX), used as a graft-versus-host disease (GvHD) prophylactic agent in hematopoietic stem cell transplantation (HSCT), exerts its effect via folate cycle inhibition. A critical enzyme involved in folate metabolism is 5,10-methylenetetrahydrofolate reductase (MTHFR). We examined the association of a single nucleotide polymorphism (SNP) at position 677 in the MTHFR gene on GvHD outcomes in allogeneic HSCT patients administered MTX. MTHFR genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) on 193 HSCT patients and donors. A total of 140 patients were transplanted with an HLA-matched related donor and 53 with an unrelated donor. GvHD outcomes were compared between genotypes by univariate and multivariate analysis. The combined donor 677CT and TT genotypes were associated with a decreased incidence of GvHD (acute and chronic combined) in HSCT recipients with an HLA-matched related donor (75% at 1 year in the CT and TT group compared with 91% in the wild type CC group, P ¼ 0.01), increased time to onset of first GvHD (P ¼ 0.001) and time to first GvHD treated with systemic therapy (P ¼ 0.022). Unrelated donor MTHFR genotype was not associated with outcome parameters and no associations of recipient genotype in either related or unrelated donor cohorts were observed.

This study examined the contribution single nucleotide polymorphisms (SNPs) of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have on clinical outcomes in hematopoietic stem cell transplant patients treated with the antiproliferative drug methotrexate. Two common SNPs, 677C>T and 1298A>C, were genotyped by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) from samples obtained from patient DNA samples. Eleven clinical outcomes including survival and graft-versus-host disease (GVHD) were assessed against donor and recipient MTHFR genotypes against pretransplantation variables. Folinic acid (FA) as treatment for oral mucositis toxicity was used at investigator discretion in 72 of 140. Donor MTHFR 1298AA genotype was associated with decreased 5-year survival (P = .03) and event-free survival (EFS) (P = .02) in patients withheld FA. Donor MTHFR 677CC genotype was associated with earlier GVHD (P = .003), and more severe acute GVHD (P = 0.02). FA was significantly associated with decreased survival (P = 0.02) in patients given a donor MTHFR 677CT transplant. FA was significantly associated with decreased survival (P = .04), EFS (P = .009) in patients given a donor MTHFR 1298AC transplant MTHFR gene polymorphisms indicate a potentially useful gene for donor selection where more than one donor is available. Use of FA following transplantation should be reconsidered in the context of patient and donor MTHFR genotypes.

In this study, susceptibility to ReA was not increased in HLA-B27 positive individuals or males but was greater in those of Caucasian descent.

The 17th International HLA and Immunogenetics Workshop (IHIW) organizers conducted a Pilot Study (PS) in which 13 laboratories (15 groups) participated to assess the performance of the various sequencing library preparation protocols, NGS platforms and software in use prior to the workshop. The organizers sent 50 cell lines to each of the 15 groups, scored the 15 independently generated sets of NGS HLA genotyping data, and generated "consensus" HLA genotypes for each of the 50 cell lines. Proficiency Testing (PT) was subsequently organized using four sets of 24 cell lines, selected from 48 of 50 PS cell lines, to validate the quality of NGS HLA typing data from the 34 participating IHIW laboratories. Completion of the PT program with a minimum score of 95% concordance at the HLA-A, HLA-B, HLA-C, HLA-DRB1 and HLA-DQB1 loci satisfied the requirements to submit NGS HLA typing data for the 17th IHIW projects. Together, these PS and PT efforts constituted the 17th IHIW Quality Control project.