Significance of the already described high-risk epitope mismatch DQA1*05+DQB1*02/DQB1*03:01 in the Munich cohort of patients after lung transplantation

Lung transplantation is a life-saving treatment for end-stage lung disease, but long-term graft survival is limited by chronic lung allograft dysfunction, often driven by alloimmune responses. Donor-specific antibodies, particularly against class II HLA-DQ molecules, are meanwhile well-known risk factors. McCaughan et al. identified HLA-DQA1*05 with DQB1*02 and/or DQB1*03:01 as high-risk epitope mismatches (REM), associated with increased incidence of de novo DSA (dnDSA). Based on our earlier findings that high-risk HLA-DQ mismatches are associated with adverse outcomes after lung transplantation, we aimed to investigate this specific mismatch pattern in our patient cohort. We analyzed 252 patients who underwent lung transplantation in Munich (2012–2021) with complete HLA typing of donors and recipients and antibody data from the first year after transplantation. All patients were DSA-negative pre-transplant and received no induction therapy. Patients with early post-transplant death or retransplantation were excluded. We examined whether REM were associated with higher risk of dnDSA development. Following McCaughan et al., DQA1*05–DQB1*02 was considered as risk epitope even in recipients who possessed the DQA*02-DQB1*02 HLA as self. Statistical analysis was performed using Fisher’s exact test. We were able to confirm our previous data, according to which approximately 25% of patients develop dnDSA within the first year after transplantation, most of them directed against HLA-DQ. 94 of 252 (37%) patients were exposed to a REM-positive donor, 153/252 (61%) to a donor with other mismatches but without REM, and 5/252 patients (2%) had no HLA-DQ mismatches. 28 of 94 patients (29.8%) developed dnDSA against these risk epitopes within the first year after transplantation. Compared to patients who were transplanted without REM (25/153), an odds ratio of 2.17 (95% CI: 1.17–4.02) was calculated (p=0.016). We were able to confirm the data published by McCaughan et al.in our patient group. With the known association between dnDSA and adverse clinical outcomes, close monitoring of patients with these high-risk DQ epitope mismatches after transplantation is already advisable in order to be able to intervene therapeutically at an early stage of dnDSA development. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany