CTLA-4 Exon 1 (+49) and Promoter (−318) Gene Polymorphisms in Kidney Transplantation

Gorgi, Yousr; Sfar, Imen; Abdallah, T. Ben; Abderrahim, E.; Ayed, S.; Aouadi, Houda; Bardi, R.; Ayed, K.

doi:10.1016/j.transproceed.2006.06.132

Cited by 29 publications

(29 citation statements)

References 11 publications

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“…In clinical transplantation, polymorphisms of the CTLA4 locus were linked with graft-versus-host diseases and acceptance of allotransplants (4,46,90,137), although conclusive evidence from a larger size of samples is still lacking. Increased frequencies of transplant rejection were associated with a polymorphism at the promoter region of the gene (−318C) that dictates only a modest reduction of CTLA4 expression (46,66,132,137), suggesting that a subtle quantitative variation of CTLA4 may reset the threshold for transplant tolerance or rejection.…”

Section: Ctla4-b7 Molecular Interaction In a “Crosstalk” Between Adapmentioning

confidence: 99%

“…Increased frequencies of transplant rejection were associated with a polymorphism at the promoter region of the gene (−318C) that dictates only a modest reduction of CTLA4 expression (46,66,132,137), suggesting that a subtle quantitative variation of CTLA4 may reset the threshold for transplant tolerance or rejection.…”

Section: Ctla4-b7 Molecular Interaction In a “Crosstalk” Between Adapmentioning

confidence: 99%

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Immune Tolerance Induction by Integrating Innate and Adaptive Immune Regulators

2010

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A diversity of immune tolerance mechanisms have evolved to protect normal tissues from immune damage. Immune regulatory cells are critical contributors to peripheral tolerance. These regulatory cells, exemplified by the CD4 + Foxp3 + regulatory T (Treg) cells and a recently identified population named myeloid-derived suppressor cells (MDSCs), regulate immune responses and limiting immune-mediated pathology. In a chronic inflammatory setting, such as allograft-directed immunity, there may be a dynamic "cross-talk" between the innate and adaptive immunomodulatory mechanisms for an integrated control of immune damage. CTLA4-B7-based interaction between the two branches may function as a molecular "bridge" to facilitate such "cross-talk." Understanding the interplays among Treg cells, innate suppressors, and pathogenic effector T (Teff) cells will be critical in the future to assist in the development of therapeutic strategies to enhance and synergize physiological immunosuppressive elements in the innate and adaptive immune system. Successful development of localized strategies of regulatory cell therapies could circumvent the requirement for very high number of cells and decrease the risks associated with systemic immunosuppression. To realize the potential of innate and adaptive immune regulators for the still elusive goal of immune tolerance induction, adoptive cell therapies may also need to be coupled with agents enhancing endogenous tolerance mechanisms.

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Section: Ctla4-b7 Molecular Interaction In a “Crosstalk” Between Adapmentioning

confidence: 99%

Section: Ctla4-b7 Molecular Interaction In a “Crosstalk” Between Adapmentioning

confidence: 99%

Immune Tolerance Induction by Integrating Innate and Adaptive Immune Regulators

2010

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“…The rs3087243 (+6230G/A) SNP is located within the 3′ untranslated region of the CTLA-4 gene and was found to be associated with susceptibility to autoimmune diseases [11]. Furthermore, the SNPs within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), play an influential role in graft rejection and the long-term clinical outcome of organ transplantation [12]–[17].…”

Section: Introductionmentioning

confidence: 99%

CTLA4 Gene Polymorphisms Influence the Incidence of Infection after Renal Transplantation in Chinese Recipients

Guo

Wei

et al. 2013

PLoS ONE

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BackgroundImmunosuppressive therapy is usually administered following renal transplantation to protect the graft from rejection. However, this often causes complications such as infections to occur. Single nucleotide polymorphisms (SNPs) within the CTLA4 gene, such as −1772T/C (rs733618), +49A/G (rs231775) and +6230 G/A (rs3087243), can affect graft rejection and the long-term clinical outcome of organ transplantation. The role of CTLA4 SNPs in T cell-mediated immunity in renal transplantation and association with infection after transplantation is unknown.MethodsIn this study, the risk of infection according to CTLA4 SNPs was investigated in 304 patients who received kidney graft transplants between 2008 and 2012.ResultsThe frequency of the rs4553808 GG genotype was significantly higher in recipients with viral infection (14.89%) than in those without infections (3.50%) (Bonferroni-adjusted p = 0.005). A significant difference (p = 0.001) in patients with the rs4553808 GG genotype from those with the AA+AG genotypes was found in the viral cohort using the log-rank test. A significant association was found between the rs4553808 genotype and onset of viral infection in transplant recipients (p = 0.001). The frequencies of the CGTAG and CGCAG haplotypes were significantly higher in the viral infection group (9.6% and 5.3%) than in the non-viral infection group (3.8% and 1.4%) (p = 0.0149 and p = 0.0111). No association between any CTLA4 SNP and bacterial infection was found. Multivariate analyses revealed that one risk factor, the use of antibody induction therapy (p = 0.007), was associated with bacterial infection, and two risk factors, antibody use (p = 0.015) and recipient rs4553808 genotype (p = 0.001), were associated with viral infection.ConclusionsThe rs4553808 GG genotype may be a risk factor for viral infection in kidney transplantation. The CTLA4 haplotypes CGTAG and CGCAG were partially associated with the development of viral infection in Chinese kidney transplant recipients.

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“…CTLA4 gene polymorphisms have been examined in relation to kidney transplantation in a few studies (Table2). An association with outcome of kidney transplantation was reported in seven genetic studies (Slavcheva et al, 2001;Gendzekhadze et al, 2006;Wisniewski et al, 2006;Gorgi et al, 2006;Kusztal et al, 2007Kusztal et al, , 2010Kim et al, 2010). On the other hand, four studies did not succeed in replicating the association with CTLA4 (Dmitrienko et al, 2005;Haimila et al, 2009b;Krichen et al, 2009Krichen et al, , 2010.…”

Section: Co-stimulator Receptor Genes May Predispose To the Poor Outcmentioning

confidence: 98%

“…A particular statistical challenge in the transplantation settings, which has not been tackled so far, is the fact that we are studying donor -recipient pairs instead of merely patients versus non-affected. Wisniewski et al, 2006;Gorgi et al, 2006;Kusztal et al, 2007Dmitrienko et al, 2005Gendzekhadze et al, 2006;Haimila et al, 2009b;Kusztal et al, 2010CTLA4+49A>G rs231775 Gendzekhadze et al, 2006Gorgi et al, 2006;Kusztal et al, 2007;Kim et al, 2010;Kusztal et al, 2010Slavcheva et al, 2001Dmitrienko et al, 2005;Wisniewski et al, 2006;Haimila et al, 2009bCTLA4(AT)n Slavcheva et al, 2001Kusztal et al, 2010Krichen et al, 2010CT60G>A rs3087243 Haimila et al, 2009bICOSivs+173T> C rs10932029 Haimila et al, 2009b ICOSc602A>C rs10183087 Haimila et al, 2009bICOSc1564C>T rs4404254 Haimila et al, 2009bICOSc1624C>T rs10932037 Haimila et al, 2009bICOSc2373G>C rs4675379 Haimila et al, 2009b Table 2. All the published genetic association studies related to T cell co-stimulatory receptors listed according to the polymorphisms examined.…”

Section: Citation Associationmentioning

confidence: 99%