In summary, we prove a role for microglia in CNS-GVHD, identify the TAK1/TNF/MHC-II axis as mediator of CNS-GVHD and provide a novel TAK1 inhibitor-based approach against GVHD-induced neurotoxicity.
As for each HLA locus, HLA-A mismatch correlated with decreased rate of platelet engraftment (HR 0.740, P = .003); HLA-B mismatch independently correlated with decreased relapse rate (HR 0.494, P = .032) and improved disease-free survival and overall survival (HR 0.514, P = .003; HR 0.494, P = .002, respectively); HLA-C mismatch appeared to be protective for transplant-related mortality (TRM) (HR 0.567, P = .039); HLA-DRB1 mismatch was associated with increased cumulative incidence of grade II-IV acute graft-vs.-host disease (GVHD) (HR 1.942, P = .002).
A significant RR of HLA allele mismatch compared with match was seen with HLA-A, -B, -C, and -DPB1 for grade III-IV acute graft-versus-host disease (GVHD), and HLA-C for chronic GVHD.
The risk of GvHD furthermore increased when recipients heterozygous for HLA-C KIR ligand groups (C1/C2) were transplanted from donors completely lacking activating KIRs (HR 6.1, 95% CI 1.9-19.2, P = 0.002).
HLA-Cw disparity in a donor increases the risk of acute graft-vs-host disease (GVHD) after bone marrow transplantation.Acute GVHD is mediated by donor CTLs.
Despite contemporary typing procedures for bone marrow transplantation (BMT), graft-versus-host disease (GVHD) continues to be a major complication of transplants performed between MHC-matched donors and recipients.
Multivariate analysis showed that incompatibility for HLA-A alleles and incompatibility for HLA-C alleles were independent risk factors for severe acute graft-versus-host disease (GVHD) (HLA-A, P=0.006; HLA-C, P=0.001).