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

AbstractHuman 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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HLA-G 14bp Ins/Del Polymorphism in the 3′UTR Region and Acute Rejection in Kidney Transplant Recipients: An Updated Meta-Analysis

Medicina ◽

10.3390/medicina57101007 ◽

2021 ◽

Vol 57 (10) ◽

pp. 1007

Author(s):

Sang Wook Kang ◽

Eunkyung Oh ◽

Wonwoo Cho ◽

Minseok Kim ◽

Eo Jin Park ◽

...

Keyword(s):

Kidney Transplantation ◽

Acute Rejection ◽

Kidney Transplant ◽

Meta Analysis ◽

Human Leukocyte ◽

Asian Population ◽

Kidney Transplant Recipients ◽

Deletion Polymorphism ◽

Transplant Patients ◽

G 14

Background and Objectives: Acute kidney injury (AKI) affects the survival rate of kidney transplant organs and patients. Acute rejection (AR) due to AKI may lead to kidney transplantation failure. It is known that there is a relationship between human leukocyte antigen-G (HLA-G), which is involved in immune regulation, and AR in transplant patients. Moreover, 14-bp insertion/deletion polymorphism in the 3′ untranslated region (UTR) region of the HLA-G gene is known to affect HLA-G expression. However, its relationship to AR is still controversial. The aim of this study was to investigate whether HLA-G 14-bp insertion/deletion polymorphism contributed to the development of AR in kidney transplant patients using a meta-analysis. Materials and Methods: To perform our meta-analysis, eligible studies about HLA-G 14-bp insertion/deletion polymorphism and AR were searched in electronic databases until 1 June 2021. Finally, a total of 336 patients with AR and 952 patients without AR in relation to kidney transplantation were analyzed from a total of nine studies. Results: In our results, the Del allele and Ins/Del+Del/Del and Del/Del genotypes significantly increased susceptibility of AR in Asian populations [odds ratio (OR) = 2.359, 95% confidence interval (CI) = 1.568–3.550, p = 3.8 × 10−5; OR = 3.357, 95% CI = 1.769–6.370, p = 0.002; OR = 2.750, 95% CI = 1.354–5.587, p = 0.0052 in each model, respectively]. Conclusions: Evidence of the present results indicate that HLA-G 14-bp insertion/deletion polymorphism is associated with susceptibility to AR in the Asian population.

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Sex-Specific Differences in HLA Antibodies after Pneumococcal Vaccination in Kidney Transplant Recipients

Vaccines ◽

10.3390/vaccines7030084 ◽

2019 ◽

Vol 7 (3) ◽

pp. 84 ◽

Cited By ~ 1

Author(s):

Lindemann ◽

Oesterreich ◽

Wilde ◽

Eisenberger ◽

Muelling ◽

...

Keyword(s):

Kidney Transplant ◽

De Novo ◽

Pneumococcal Vaccination ◽

Human Leukocyte ◽

Hla Class I ◽

Current Data ◽

Class I ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Hla Antibodies

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.

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