CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors.

Pérez-García, Arianne; Cámara, Rafael de la; Román‐Gómez, José; Jiménez-Velasco, Antonio; Encuentra, Maite; Nieto, José; Rubia, Javier de la; Urbano-Ispizúa, Álvaro; Brunet, Salut; Iriondo, A; González, Marcos; Serrano, David; Espigado, Ildefonso; Solano, Carlos; Ribera, Josep‐Marǐa; Pujal, Josep María; Hoyos, Montserrat; Gallardo, David

doi:10.1182/blood-2007-01-069781

Cited by 80 publications

(106 citation statements)

References 37 publications

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“…It has been reported that the CT60 A allele is associated with a higher level of the sCTLA-4 mRNA than the CT60 G allele. 17,28 These results indicate that the À318 C allele and the CT60 A allele contribute to the reduction in CTLA-4 inhibitory function and to T-cell activation. However, association of the þ 49 A allele with a higher expression of CTLA-4 and augmentation of CTLA-4 inhibitory function has been reported.…”

Section: Discussionmentioning

confidence: 79%

“…However, it might be because of our small cohort, as Perez-Garcia et al 17 demonstrated that the donor CT60 AA genotype was associated with an increased risk of grade II-IV acute GVHD in a large cohort of 536 donors. All of the patients in our study were Japanese, and many of them (75%) had received BM as a stem-cell graft.…”

Section: Discussionmentioning

confidence: 83%

“…It has been shown that the donor À318 C allele is associated with a lower risk of relapse 19 and that the donor CT60 AA genotype correlates with a lower risk of relapse and a higher OS. 17 Therefore, we focused on the C-A-A haplotype from three different haplotypes in the Japanese population, and examined the association between the C-A-A haplotype and the outcome after allogeneic HSCT. The presence of the CTLA-4 C-A-A haplotype exhibited a significantly lower incidence of relapse and a trend toward of a higher survival rate compared with the absence of the haplotype C-A-A, suggesting that the C-A-A haplotype might suppress the inhibitory function of CTLA-4 on tumor-reactive T cells and enhance the GVL effect.…”

Section: Discussionmentioning

confidence: 99%

“…17 We therefore focused our analysis on the C-A-A haplotype, and examined the association between the C-A-A haplotype and the outcome after allogeneic HSCT. The incidence of grade II-IV acute GVHD was 19% for all patients (Table 1).…”

Section: Frequencies Of Ctla-4 Genotypes and Haplotypesmentioning

confidence: 99%

“…16 In addition, recent studies have shown an association of the CTLA-4 polymorphisms (À318 (rs5742909), þ 49 (rs231775) and CT60 (rs3087243)) with outcome after allogeneic HSCT. [17][18][19] We therefore focused our study on these three polymorphisms, and analyzed the impact of donor genotypes and haplotypes in the Japanese population on outcome after HLA-identical sibling HSCT.…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT

Murase

Nishida

Onizuka

et al. 2010

Bone Marrow Transplant

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Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Frequencies Of Ctla-4 Genotypes and Haplotypesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT

Murase

Nishida

Onizuka

et al. 2010

Bone Marrow Transplant

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Genetic Polymorphisms in the Cytokine and Chemokine System: Their Possible Importance in Allogeneic Stem Cell Transplantation

Loeffler

Morton

et al. 2010

The Chemokine System in Experimental and Clinical Hematology

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Chemokines represent central players of the innate and adaptive immunity and are involved in the regulation of inflammatory events occurring during infectious complications or during graft vs. host disease (GvHD). Patients after allogeneic stem cell transplantation (alloSCT) are at a high risk for the development of acute GvHD or to suffer from fungal infections. Susceptibility to fungal infections and the course of GvHD can be genetically influenced by single nucleotide polymorphisms (SNPs), which regulate expression or biological activity of chemokines, and therefore have an impact on the outcome of invasive aspergillosis and GvHD. High lightened studies of abetting factors for GvHD revealed SNPs in TNFA, IL-6, IL-10, INF-γ, CCL2, CCL5 (RANTES), IL-1Ra, IL-23R, IL-7Ralpha, IL-10RB, and CCR9 genes as prevalent considerable. Furthermore, additional SNPs were described to be significantly associated with fungal infections (Aspergillus fumigatus, Candida albicans), including markers in CCL3, CCL4, CCL20, CXCL2, CXCL8, CXCL10, CCR1, and CCR2. This review summarizes the current knowledge about the growing number of genetic markers in chemokine genes and their relevance for patients after alloSCT.

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A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation

Karabon

Markiewicz²,

Partyka

et al. 2015

Immunogenetics

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T cell activation plays a crucial role in the development of acute graft versus host disease (aGvHD). Cytotoxic T cell antigen-4 (CTLA-4) is a co-inhibitory molecule that negatively regulates T cell activation, differentiation, and proliferation. Single-nucleotide polymorphisms (SNPs) in CTLA-4 gene may affect its function. Inconsistent observations have been reported regarding the associations of CTLA-4 SNPs with complications after hematopoietic stem cell transplantation (HSCT). Moreover, the majority of the observations were focused on the donors’ SNPs. Recently, a few studies have shown that recipients’ genetic variations in the CTLA-4 gene might influence HSCT results. The aim of our study was to determine the influence of the CTLA-4 gene polymorphisms of the donors and the recipients on the outcome of HSCT. Altogether, 312 donor-recipient pairs were genotyped for the CTLA-4c.49A>G (rs231775) and CT60G>A (rs3087243) SNPs using the TaqMan®SNP Genotyping Assays. In this study, it was shown that the recipients’ CT60G>A[GG] genotype, the myeloablative conditioning regimen, and HSCT from an unrelated donor were independent aGvHD risk factors (odds ratio (OR) 2.63, 95 % confidence intervals (95 % CI) 1.45–4.59, p = 0.001; OR 2.68, 95 % CI 1.65–4.07, p = 0.00003; and OR 1.87, 95 % CI 1.02–3.24, p = 0.04, respectively). Moreover, haplotype analysis revealed that possessing allele A in both of the SNPs decreased the risk of aGvHD approximately 1.5-fold (RR 0.69, p = 0.008). Our data suggest that the CT60G>A[GG] genotype in the recipient has an impact on aGvHD development, especially in patients receiving transplants from unrelated donors together with the myeloablative conditioning regimen.

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CTLA-4 polymorphisms and clinical outcome after allogeneic stem cell transplantation from HLA-identical sibling donors.

Abstract: CTLA-4 is an inhibitory molecule that

Cited by 80 publications

References 37 publications

Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT

Cytotoxic T-lymphocyte antigen 4 haplotype correlates with relapse and survival after allogeneic hematopoietic SCT

Genetic Polymorphisms in the Cytokine and Chemokine System: Their Possible Importance in Allogeneic Stem Cell Transplantation

A CT60G>A polymorphism in the CTLA-4 gene of the recipient may confer susceptibility to acute graft versus host disease after allogeneic hematopoietic stem cell transplantation

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