The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes

Niknam, Ahmad; Karimi, Mohammad Hossein; Yaghobi, Ramin; Geramizadeh, Bita; Roozbeh, Jamshid; Salehipour, Mehdi; Iravani, M

doi:10.5812/jjm.31338

Cited by 7 publications

(6 citation statements)

References 51 publications

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“…The significance of the association of LILRB1 SNPs with HCMV disease is that it may be useful as part of a collection of biomarkers used to determine the relative risk for patients after receiving a transplant and to guide prophylactic use of antivirals in these patients. Many studies have investigated genetic influences on the immune response to HCMV; the genes implicated in modulating the control of HCMV after transplantation include IL-28B, CCL8, several microRNA, CLTA4, TLR9, DC-SIGN, and, most relevant to NK cells, NKG2C and KIRs (40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56). Further studies with additional cohorts could be useful to pinpoint the SNPs with the best correlation and to explore the relationship to the sequence of UL18 within each patient.…”

Section: Genotyping Of Transplant Patientsmentioning

confidence: 99%

LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions

Yu¹,

Davidson²,

Wójtowicz³

et al. 2018

Journal of Clinical Investigation

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UL18 is a human CMV (HCMV) MHC class I (MHCI) homolog that efficiently inhibits leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1)+ NK cells. We found an association of LILRB1 polymorphisms in the regulatory regions and ligand-binding domains with control of HCMV in transplant patients. Naturally occurring LILRB1 variants expressed in model NK cells showed functional differences with UL18 and classical MHCI, but not with HLA-G. The altered functional recognition was recapitulated in binding assays with the binding domains of LILRB1. Each of 4 nonsynonymous substitutions in the first 2 LILRB1 immunoglobulin domains contributed to binding with UL18, classical MHCI, and HLA-G. One of the polymorphisms controlled addition of an N-linked glycan, and that mutation of the glycosylation site altered binding to all ligands tested, including enhancing binding to UL18. Together, these findings indicate that specific LILRB1 alleles that allow for superior immune evasion by HCMV are restricted by mutations that limit LILRB1 expression selectively on NK cells. The polymorphisms also maintained an appropriate interaction with HLA-G, fitting with a principal role of LILRB1 in fetal tolerance.

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Section: Genotyping Of Transplant Patientsmentioning

confidence: 99%

LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions

Yu¹,

Davidson²,

Wójtowicz³

et al. 2018

Journal of Clinical Investigation

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“…There are two single nucleotide polymorphisms in the first exon of the TGF-β1 gene which increase the expression of the gene: +869T>C and +915G>C. In vitro studies showed that the genetic polymorphisms of TGF-β1 codon 10 T>C and codon 25 C>G result in increased production of this cytokine. The highest expression was observed in TT homozygous for TGF-β1 codon 10 T>C and GG genotype for TGF-β1 codon 25 C>G 23 . In addition, numerous studies demonstrated an association of the TGF-β1 gene with chronic renal transplant rejection and CsA toxicity 24 – 26 .…”

Section: Discussionmentioning

confidence: 90%

Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation

Bogacz

Wolek

Sieńko

et al. 2021

Sci Rep

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Organ transplant is often the treatment of choice as it extends and improves patient life. Immunosuppressive treatment, which prevents acute rejection of the organ, is used in transplant patients to prevent the loss of transplant. The aim of the study was to determine the impact of the CTLA4 (+49A>G, rs231775) and the TGF-β1 (−800G>A, rs1800468) polymorphisms on the therapeutic effect of immunosuppressive drugs (cyclosporine—CsA, tacrolimus—TAC) and the risk of acute rejection in renal transplant patients. The analysis of the CTLA4 +49A>G and the TGF-β1 −800G>A polymorphisms was carried out in 392 patients after kidney transplant using real-time PCR. The CTLA4 +49A>G polymorphism did not affect CsA or TAC dose, ratio of drug concentration to dose (C/D), and blood concentrations. As for the TGF-β1 -800G>A polymorphism, patients with the GA genotype required lower TAC doses compared to the GG genotype (TAC 12 h: 3.63 mg vs 5.3 mg, TAC 24 h: 2.38 mg vs 3.29 mg). Comparing the C/D ratio in both groups (TAC 12 h and TAC 24 h), higher C/D ratio was observed in patients with the GA genotype. These results indicate that patients with the A allele require slightly lower doses of TAC. The results suggest that the TGF-β1 −800 G>A polymorphism may influence the TAC dose, while the +49A>G polymorphism of the CTLA4 gene does not correlate with the dose of CsA or TAC. The analysis of the biochemical parameters of the renal profile showed no impact of the CTLA4 and the TGF-β1 polymorphisms on the risk of organ rejection.

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“…Various studies found that rs733618 SNP significantly correlated with many immune diseases. Niknam et al [ 21 ] demonstrated that -1722C allele negatively associated with acute rejection in kidney transplant patients with active Cytomegalovirus infection. A potential of rs733618 SNP also has been discovered in autoimmune myasthenia gravis.…”

Section: Discussionmentioning

confidence: 99%

Correlation between CTLA4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion

Liu

Qin

et al. 2018

Medicine

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Present study was aimed to detect the influence of cytotoxic T-lymphocyte associated protein 4 (CTLA4) gene polymorphisms for the risk of recurrent spontaneous abortion (RSA), as well as the serum level of CTLA4 protein in RSA patients.One hundred thirty-three RSA patients and 146 healthy persons were recruited in this case–control study. PCR-RFLP was used to genotype the CTLA4 gene polymorphisms both in case and control groups. Serum level of CTLA4 was detected by ELISA kit. Quantitative variables were compared by t test or Mann–Whitney U test between groups. Qualitative variables were evaluated by χ2 test or Fisher exact test. Association strength was expressed by odds ratios (ORs) and 95% confidence intervals (95% CIs).G allele of rs4553808 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) and T allele of rs5742909 (P = .027, OR = 0.570, 95% CI = 0.345–0.942) were distinctly associated with reduced susceptibility of RSA. Distinctly negative association has been discovered between rs231775 AA genotype and RSA susceptibility (P = .040, OR = 0.427, 95% CI = 0.188–0.973). CTLA4 protein had significantly higher serum level in RSA patients than in healthy controls (P = .028). In RSA patients, AA genotype carriers had higher CTLA4 serum level than that GG genotype carriers (17.83 ± 6.35 ng/mL vs 10.41 ± 7.28 ng/mL, P = .039).Minor alleles of CTLA4 polymorphisms might inhibit the RSA susceptibility via upregulated the protein expression level.

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The Association Between Viral Infections and Co-stimulatory Gene Polymorphisms in Kidney Transplant Outcomes

Cited by 7 publications

References 51 publications

LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions

LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions

Influence of TGFB1 and CTLA4 polymorphisms on calcineurin inhibitors dose and risk of acute rejection in renal transplantation

Correlation between CTLA4 genetic polymorphisms, its serum protein level and the susceptibility to recurrent spontaneous abortion

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