The role of genetic variants of NOD2/CARD15, a receptor of the innate immune system, in GvHD and complications following related and unrelated donor haematopoietic stem cell transplantation.
Previous studies from our group indicated a role of SNPs within the innate immunity receptor NOD2/CARD15 as a risk factor for GvHD and treatment-related mortality allogeneic stem cell transplantation from HLA-identical siblings. We now extended these studies to assess the role of NOD2/CARD15 SNPs in 342 unrelated donor transplants. Overall, presence of any SNPs in patients or donor resulted in an increased risk of severe GvHD (25% in wildtype versus 38% in recipients and donors with variants, P= 0.01), which did not translate in increased mortality. When the analysis was broken down to individual SNPs, the presence of a SNP13 in the donor turned out to be the only highly significant risk factor (GvHD III/IV 22% wt, 42% SNP13 donor, P < 0.004; TRM 33% wt versus 59% SNP13 donor, P= 0.01; overall survival 49% wt versus 26% SNP13 donor, P= 0.007). This association was confirmed in multivariate analysis. Analysis of clinical risk factors suggested that this effect was most prominent in patients receiving any form of T cell depletion. Thus our observation indicates that the presence of a defect in innate immunity signalling in donor monocytes and possibly antigen presenting cells is most prominent in patients having additional T cell deficiency.
Holler
E
E
Department of Haematology/Oncology, University of Regensburg, Regensburg, Germany. ernst.holler@klinik.uni-regensburg.de
Rogler
G
G
Brenmoehl
J
J
Hahn
J
J
Greinix
H
H
Dickinson
A M
AM
Socie
G
G
Wolff
D
D
Finke
J
J
Fischer
G
G
Jackson
G
G
Rocha
V
V
Hilgendorf
I
I
Eissner
G
G
Marienhagen
J
J
Andreesen
R
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D002985:Clinical Protocols; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006086:Graft vs Host Disease / Q000235:genetics* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D006801:Humans; D007113:Immunity, Innate; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014019:Tissue Donors; D055815:Young Adult
C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein