The donor-recipient sex-related mismatch has been reported as a risk factor for acute graft-versus-host disease (GVHD). However, the results obtained in previous studies appear to be contradictory. Here we evaluate the impact of donor-recipient sex-related mismatch in a series of 204 Sardinian individuals (92.1% of them affected by Beta- Thalassemia major) who underwent bone marrow transplantation (BMT) from human leukocyte antigen (HLA) identical siblings. In all, 78 of these patients had acute GVHD (aGVHD). We found that also in this homogenous group of patients from a homogenous population, the donor-female/recipient-male pair provided an increased risk for aGVHD when compared with a reference donor-male/recipient-male pair (POR=2.3, P=0.042). This data could be consistent with a role of variation in the male-specific portion of the Y chromosome in aGVHD. To assess this, we compared the distribution of the main Y-chromosome haplogroups in 28 male patients, who had aGVHD and underwent BMT from HLA-identical sisters, and 366 ethnically-matched controls. No significant differences were observed. These findings do not support the presence of Y chromosome founder variants contributing significantly to aGVHD in the Sardinian population.
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