Dataset Information

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

ABSTRACT:

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-?(+?869?T?>?C,+915C?>?G), IL-6(-174G?>?C), tumor necrosis factor-?(-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.

Conclusions

The study of transplanted patients allowed to evidence a potential relationship between post-transplant weight gain and HLA-G14bp ins/del polymorphism, previously involved in rejection for its immunosuppressive/tolerogenic activity. This novel association could widen the knowledge of the role and functions of HLA-G molecules in diseases and transplantation.

SUBMITTER: Piancatelli D

PROVIDER: S-EPMC7104538 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Piancatelli Daniela D Maccarone Daniela D Colanardi Alessia A Sebastiani Pierluigi P Clemente Katia K Iesari Samuele S Lai Quirino Q Pisani Francesco F

BMC nephrology 20200330 1

<h4>Background</h4>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 fa ...[more]

PMID: 32228494

Similar Datasets

Project description:Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients. A total of 46 PBMC samples representing blood draws from four time points in the first 9 recipients were processed for microarray analysis (The Scripps Research Institute, La Jolla, CA). The analyzed time points were: immediately pre-operatively in the absence of immunosuppression (n=9); post-operatively at 1 year (n=8, range 11-13 months); at 2 years (n=12, range 18-25 months); >3 years (n=17, range 32-48 months). (At year 2 and at > 3 years, repeated samples were obtained from individual subjects, and at one year, one subject had a technically unsatisfactory sample.) To discount the effects of immunosuppression on gene expression, microarray data were included on whole blood from 18 healthy human subjects (controls: GSE40586; NCBI Gene Expression Omnibus [GEO] repository).

Project description:BackgroundRenal transplantation is the definitive treatment for patients with end-stage renal disease (ESRD). It is associated with better quality of life and patient survival. Nevertheless, these benefits come with rising concerns about weight gain and metabolic abnormalities, which adversely impact transplant outcomes.ObjectiveThe objective of this study is to estimate the incidence of weight gain in the first year post-renal transplant in addition to the assessment of potential risk factors and the resulting outcome of the graft.MethodsWe conducted a single-center retrospective cohort study of all 295 patients who underwent kidney transplantation at King Abdulaziz Medical City (KAMC) between January 2016 and December 2019. Clinical and laboratory variables were collected from electronic records. Continuous variables were reported as mean ± standard deviation. Comparison between groups was assessed by unpaired t-test or Mann-Whitney U test while follow-up data were compared using paired t-test and repeated measures ANOVA. Association between the potential risk factors and the weight gain was assessed by means of binary logistic regression analysis.ResultsSignificant weight gain was observed in 161 (54.6%) patients. Females were 119 (40.30%) of the cohort. The mean age was 45.3±15.1 years. The prevalence of diabetes was 234 (79.6%), while hypertensives constituted 77 (26.3%). The comparison between patients who gained weight significantly and patients with stable weight showed a numerical higher prevalence of female gender in patients who had more weight gain (44.1% vs. 35.8%), higher diabetes, higher rate of a living donor, and statistically significant lower dialysis duration before transplant. Other clinical and laboratory variables were comparable between the two groups.ConclusionOur study showed a high incidence of clinically significant weight gain among patients post-renal transplantation. Patients with lower dialysis duration, a living kidney donor and those who are obese at baseline were at higher risk of gaining weight. Patients who underwent kidney transplantation should be monitored closely for weight gain and further studies are needed to determine the risk factors and appropriate interventions.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets