Auswirkungen von Minor Histokompatibilitätsantigen Mismatchen auf die unverwandte, allogene hämatopoetische Stammzelltransplantation
Auch gedruckt in der BibliothekW: W-H 13.167
Ressourcen- / MedientypDissertation, Text
Datum der Freischaltung2013-01-24
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.
MeSHMinor histocompatibility antigens
Stem cell transplantation
Freie SchlagwörterHämatopoetische Stammzelltransplantation