Auswirkungen von Minor Histokompatibilitätsantigen Mismatchen auf die unverwandte, allogene hämatopoetische Stammzelltransplantation
Minor Histocompatibility Antigens (mHag) are polymorphic peptides arising from Single Nucleotide Polymorphisms (SNP) in cytosolic proteins. When presented by class I or II MHC molecules, mHag can induce cellular immune responses such as transplant rejection, graft-versus-host-disease (GvHD) and the curative graft-versus-leukaemia-effect (GvL) after HSCT in individuals lacking the same allelic variant. We determined the allelic dimorphisms of the mHag HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, PANE-1 and UGT2B17 as well as SNP’s in the cell adhesion molecules CD31 and CD62L by PCR-SSP typing (mHag TS-PCR-SSP Minitray Kit, CTS Heidelberg) in 320 HSCT patients and their unrelated donors. Overall survival, grades II-IV acute GvHD (aGvHD), treatment related mortality (TRM) and relapse/disease recurrence were correlated with the mHag matching grade. In the HLA-B44-positive group (n=77), patients with a single ACC-2 GvH Mismatch had an increased overall survival (p=0,04, HR:2,44, CI:1,06-5,62), due to a lower TRM rate (p=0,03, HR:0,34, CI:0,13-0,87). The same finding (overall survival: p= 0,003, HR:2,4, CI:1,34-4,36, TRM: p= 0,03, HR:0,45, CI: 0,22-0,92) was detected for patients with CD62L Codon 206 Mismatch in the HLA-A3 superfamily group (n=140). After correction for multiple testing, only CD62L Codon 206 GvH Mismatch remained as a significant factor positively influencing the overall survival rate in mismatched donor recipient pairs (p=0,04). This observation could not be attributed to any secondary outcome factor such reduced risk for TRM (p= 0,09) or disease recurrence (p= 0,93). Based on this analysis, we conclude that mHag mismatches at HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, PANE-1, UGT2B17 and CD31 have no important effect on the clinical outcomes after unrelated HSCT. In contrast, mismatches on the adhesion molecule CD62L are significantly associated with a higher overall survival.
Subject HeadingsMinor histocompatibility antigens [MeSH]
Stem cell transplantation [MeSH]