Expression of HLA-G transcripts in graft biopsy samples of renal transplant recipients

Žilinská, Zuzana; Bandžuchová, Helena; Chrastina, Martin; Trebatický, B.; Breza, J; Handzušová, Martina; Kuba, Daniel; Tirpáková, Jana; Pavlechová, Mária; Dedinská, Ivana; Rychlý, Boris; Poláková, K

doi:10.1016/j.trim.2015.10.001

Cited by 13 publications

(6 citation statements)

References 26 publications

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“…Many studies observed that higher serum HLA-G level or HLA-G mRNA expression is associated with kidney graft acceptance [8,18,[20][21][22][23]26,31]. The authors have suggested that soluble HLA-G could be used as additional marker to monitor the graft acceptance outcome.…”

Section: Discussionmentioning

confidence: 99%

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Impact of HLA-G 14 bp polymorphism and soluble HLA-G level on kidney graft outcome

Ďurmanová

Bandžuchová²,

Žilinská

et al. 2016

Open Life Sciences

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Human leukocyte antigen G (HLA-G) is a non-classical HLA class I protein with various immunosuppressive functions. Besides its profound effect to induce fetal tolerance, HLA-G has been also found to enhance graft acceptance. The aim of the study was to analyse the association between HLA-G 14 bp insertion/deletion polymorphism, soluble HLA-G level and kidney graft outcome in the Slovak population. We investigated 69 kidney transplant recipients aged 27–65 years. Out of this group, 37 recipients developed acute rejection, confirmed by biopsy, and 32 patients had stable allograft function. Plasma was obtained from recipients at 1 day before transplantation and analyzed by ELISA. Genotyping of HLA-G polymorphism was performed by PCR. Significantly higher pre-transplantation levels of sHLA-G were found in the group with stable allograft function in comparison to group with acute rejection (P = 0.0409). In the homozygous −14/−14 recipients with stable allograft function, significantly higher values of sHLA-G were determined in comparison to the recipients with acute rejection (P = 0.0052). The study revealed an association between 14 bp deletion polymorphism and soluble HLA-G level that is proportional to kidney graft acceptance. It is suggested that pre-transplantation levels of soluble HLA-G should be monitored as additional marker to predict kidney graft outcome.

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Section: Discussionmentioning

confidence: 99%

“…The clinical characteristics of the recipients are shown in Table 1. Immunosuppressive drugs were administered for the first 1-2 days after transplantation as described by Zilinska et al [26]. Written informed consent for enrolling in the study and for personal data management was obtained from all recipients.…”

Section: Study Subjectsmentioning

confidence: 99%

Impact of HLA-G 14 bp polymorphism and soluble HLA-G level on kidney graft outcome

Ďurmanová

Bandžuchová²,

Žilinská

et al. 2016

Open Life Sciences

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“…However, associations between HLA-G14bp genotypes and rejection were investigated, with inconclusive results [13][14][15]: an association of HLA-G14bp ins/ins genotype with acute rejection was found, although in a limited number of patients [13] and recipients with acute rejection were found to have lower soluble HLA-G (sHLA-G) levels [15]. Instead, HLA-G mRNA in graft biopsies was significantly higher in acute rejection, in comparison with patients with no rejection [16].…”

Section: Introductionmentioning

confidence: 99%

HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation: potential implications beyond tolerance

et al. 2020

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Background: Human leukocyte antigen (HLA)-G is a non-classical HLA molecule with immunomodulant and immunosuppressive functions, involved in transplantation tolerance. HLA-G14bp ins/del polymorphism in exon 8 has been associated with allograft rejection and kidney transplant outcome, with controversial results. We investigated associations of HLA-G14bp ins/del polymorphism on onset of some of the main post-transplant risk factors, like excess body weight, lipid abnormalities, increased fasting plasma glucose. Polymorphisms of cytokines with both immunosuppressive and metabolic effects were also assessed for comparisons and associated analysis. Methods: The present study involved kidney transplant recipients (n = 173) in which body mass index, cholesterol, triglycerides, fasting plasma glucose were registered in the first years after transplantation and analyzed in association with genotypes. Presence of hypertension and smoking habits, demographic, transplant-related and therapeutic data of patients were also recorded. Polymerase chain reaction, sequence-specific primer amplification and Taqman allelic discrimination techniques were used for genotyping of HLA-G14bp ins/del, interleukin (IL)-10(−1082G > A,-819 T > C,-592A > C), transforming growth factor-β(+ 869 T > C,+915C > G), IL-6(−174G > C), tumor necrosis factor-α(−308G > A) and IL-18(−137G > C,-607C > A). Effects of genotypes on clinical markers at each time point (pre-transplant and 1 to 5 years after transplant) were analyzed using a repeated-measures general linear model analysis; adjustment for potential confounders was performed. Results: Results showed that HLA-G14bp ins/ins was significantly associated with obesity, in particular after transplantation (3 years, p = 0.002, OR = 4.48, 95% CI:1.76-11.41). Post-transplant body mass index was significantly increased in HLA-G14bp ins/ins carriers (3 and 4 years, p = 0.033 and p = 0.044); effects of HLA-G14bp genotypes on post-transplant BMI were confirmed by using repeated-measures analysis and after controlling for confounding variables. Cytokine genotypes did not associate with the examined factors.

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“…Furthermore, Zilinska et al . showed that HLA-G mRNA expression was increased in recipients with acute rejection such as AMR and T cell-mediated rejection as compared to patients with dysfunctional non-rejected grafts [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression

et al. 2018

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Human leukocyte antigen (HLA)-DRB3 is a functional HLA class II gene, which has a limited allele diversity in the human population. Furthermore, the HLA-DRB3 gene is only present in a subset of individuals. Therefore, in organ transplantation, this HLA molecule is frequently mismatched between patient and graft donor and thus antibodies against this mismatched HLA molecule can develop. In this study, we aimed to evaluate the prevalence and reactivity of these antibodies and aimed to identify factors that underlie antibody formation against HLA-DRB3. We showed in our patient cohort that HLA-DRB3 antibodies are identified in about 7% of all patients that were screened with solid phase assays. In these assays, we observed multiple antibody reactivity patterns indicating that HLA-DRB3 harbours multiple epitopes. In those cases, where we succeeded at tracing back the induction of these antibodies to the molecular HLA typing of the immunogenic event, we noticed a different frequency of HLA-DRB1 allele groups in the donors as compared to a control group. To a certain extent this distribution (e.g. HLA-DRB1*11 individuals) could be linked to an altered expression level. However, it also appears that different HLA-DRB3 alleles (e.g. HLA-DRB3*01 group) vary in their immunogenicity without having an expression difference. In conclusion, our study provides information on the immunogenicity and reactivity patterns of antibodies against HLA-DRB3 in kidney transplantation, and it points towards the possibility of HLA expression as a factor underlying antibody formation.

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Expression of HLA-G transcripts in graft biopsy samples of renal transplant recipients

Cited by 13 publications

References 26 publications

Impact of HLA-G 14 bp polymorphism and soluble HLA-G level on kidney graft outcome

Impact of HLA-G 14 bp polymorphism and soluble HLA-G level on kidney graft outcome

HLA-G14bp ins/del polymorphism and post-transplant weight gain in kidney transplantation: potential implications beyond tolerance

The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression

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