NOD2/CARD15 gene polymorphisms affect outcome in pediatric allogeneic stem cell transplantation

Kreyenberg, Hermann; Jarisch, Andrea; Bayer, Christina; Schuster, Blanca; Willasch, André; Strahm, Brigitte; Kremens, Bernhard; Gruhn, Bernd; Schrauder, André; Burdach, Stefan; Führer, Monika; Kabisch, H; Schlegel, Paul-Gerhard; Stachel, Daniel; Beck, James F.; Mauz-Koerholz, Christine; Chung, Tje Lin; Holler, Ernst; Klingebiel, Thomas; Bader, Peter

doi:10.1182/blood-2011-05-356451

Cited by 9 publications

(8 citation statements)

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“…The influence of NOD2 SNPs (8,12,13) in both donors and recipients was stronger and statistically significant in a subgroup of recipients of MUD transplants who received ATG as part of a conditioning regimen (4 of 7 versus 31 of 228, P ¼ .008, chi-square test with Yates' correction). The latter subgroup of patients were further analyzed.…”

Section: Nod2 Mutations and Agvhd Risk In Recipients Of Unrelated Donmentioning

confidence: 94%

“…Hematopoietic stem cell transplant (HSCT) recipients are susceptible to microbial infections, including viral reactivation due to the period of weeks in which there is a lack of optimal number of both innate and adaptive immunity involved cells. Several papers on the role of NOD2 mutation in the course of HSCT have not brought conclusive results so far [11][12][13][14][15][16][17]. Most of the authors analyzed the incidence of aGVHD, rather than infections.…”

Section: Introductionmentioning

confidence: 99%

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NOD2/CARD15 Single Nucleotide Polymorphism 13 (3020insC) is Associated with Risk of Sepsis and Single Nucleotide Polymorphism 8 (2104C>T) with Herpes Viruses Reactivation in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Jaskuła

Lange

Kyrcz‐Krzemień

et al. 2014

Biology of Blood and Marrow Transplantation

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Three NOD2 polymorphisms (single nucleotide polymorphism [SNP]8 [2104C>T, Arg702Trp], SNP12 [2722G>C, Gly908Arg], and SNP13 [3020insC, Leu1007 fsins C]), identified as disease-associated variants in Crohn's disease, have recently been suggested as gene markers of the outcome of hematopoietic stem cell transplantation (HSCT). In the present multicenter study of 464 donor-recipient pairs, we focused on the effect of NOD2 mutation(s) on the risk of infections and acute graft-versus-host disease (aGVHD). The presence of SNP13 in recipients, donors, or both was more frequently seen in patients having sepsis than in those lacking sepsis (9 of 48 versus 33 of 386, P = .046). The presence of SNP8 (recipient and/or donor positive) was associated with a higher rate of Herpes viruses reactivation (17 of 21 versus 86 of 173, P = .007). In the SNP8-positive group, a trend for a higher rate of bacteremia well controlled by antibiotics was found (9 of 10 versus 47 of 81, P = .106). In contrast, the presence of SNP13 in recipient and/or donor resulted in a poor response to antibiotics (5 of 11 versus 9 of 10, P = .042). A statistically significant association between the presence of NOD2 SNPs and acute grade > II GVHD was found in a subgroup of HSCT patients who received transplants from unrelated donors with a myeloablative conditioning regimen that included antithymocyte globulin (ATG). In this subgroup of patients, donor positivity for any SNPs investigated (7 of 18 versus 17 of 113, P = .036) and, independently, only the presence of SNP8 (4 of 8 versus 20 of 123, P = .055) were associated with severe grade ≥ II aGVHD. In conclusion, SNP8 positivity in donors or recipients makes patients more prone to Herpes viruses reactivation and bacteremia but not to sepsis. Septic complications were associated with SNP13 polymorphism. SNP8 in donors constitutes a risk factor of severe aGVHD, but only if patients received transplants from unrelated donors and received ATG as part of a conditioning regimen.

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Section: Nod2 Mutations and Agvhd Risk In Recipients Of Unrelated Donmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

NOD2/CARD15 Single Nucleotide Polymorphism 13 (3020insC) is Associated with Risk of Sepsis and Single Nucleotide Polymorphism 8 (2104C>T) with Herpes Viruses Reactivation in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Jaskuła

Lange

Kyrcz‐Krzemień

et al. 2014

Biology of Blood and Marrow Transplantation

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“…A brief communication published last year highlighted the impact of NOD2 SNPs in a large, multicentre, paediatric cohort [86]. A total of 567 HSCT pairs were tested.…”

Section: Nod2 Polymorphism and The Outcome Of Hsctmentioning

confidence: 99%

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome

Mayor

Shaw

Madrigal

et al. 2012

Bone Marrow Research

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Haematopoietic stem cell transplantation (HSCT) is a valuable tool in the treatment of many haematological disorders. Advances in understanding HLA matching have improved prognoses. However, many recipients of well-matched HSCT develop posttransplant complications, and survival is far from absolute. The pursuit of novel genetic factors that may impact on HSCT outcome has resulted in the publication of many articles on a multitude of genes. Three NOD2 polymorphisms, identified as disease-associated variants in Crohn's disease, have recently been suggested as important candidate gene markers in the outcome of HSCT. It was originally postulated that as the clinical manifestation of inflammatory responses characteristic of several post-transplant complications was of notable similarity to those seen in Crohn's disease, it was possible that they shared a common cause. Since the publication of this first paper, numerous studies have attempted to replicate the results in different transplant settings. The data has varied considerably between studies, and as yet no consensus on the impact of NOD2 SNPs on HSCT outcome has been achieved. Here, we will review the existing literature, summarise current theories as to why the data differs, and suggest possible mechanisms by which the SNPs affect HSCT outcome.

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“…It was first reported by Elmaagacli et al (2006) that the NOD2 polymorphisms (rs2066844 or SNP8, rs2066845 or SNP12, rs2066847 or SNP13), are associated with risk for aGvHD; specifically, patients transplanted with cells from a donor harbouring the mutated allele were less likely to have aGvHD (Elmaagacli et al, 2006). However, some later studies found this association not to be significant (Gruhn et al, 2009;Kreyenberg et al, 2011). van der Velden et al (2011) argued that specific characteristics of HSCT performed, e.g.…”

Section: Nod2/card15mentioning

confidence: 99%

From genetic single candidate gene studies to complex genomics of GvHD

Bogunia‐Kubik

Łacina

2017

Br J Haematol

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Graft-versus-host disease (GvHD) is a serious complication affecting the recipients of allogeneic haematopoietic stem cells. In this present review we attempt to summarize the current knowledge on the effect of the donor and recipient genotypes on GvHD, starting from human leucocyte antigen (HLA) matching for an optimal donor selection, typing of non-classical HLA and minor histocompatibility antigens through the polymorphic variations in genes coding for non-HLA proteins contributing to the development of GvHD and response to treatment. The results of recent Candidate Gene Studies (CGS) and Genome-Wide Association Studies (GWAS) are presented and discussed.

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NOD2/CARD15 gene polymorphisms affect outcome in pediatric allogeneic stem cell transplantation

Cited by 9 publications

References 9 publications

NOD2/CARD15 Single Nucleotide Polymorphism 13 (3020insC) is Associated with Risk of Sepsis and Single Nucleotide Polymorphism 8 (2104C>T) with Herpes Viruses Reactivation in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

NOD2/CARD15 Single Nucleotide Polymorphism 13 (3020insC) is Associated with Risk of Sepsis and Single Nucleotide Polymorphism 8 (2104C>T) with Herpes Viruses Reactivation in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

NOD2 Polymorphisms and Their Impact on Haematopoietic Stem Cell Transplant Outcome

From genetic single candidate gene studies to complex genomics of GvHD

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