LONG-TERM SURVIVAL OF THE TRANSPLANTED KIDNEY AND THE CLINICAL RELEVANCE OF DONOR-SPECIFIC ANTIBODIES

The aim of our study was to evaluate the relevance of donor-specific antibodies (DSA) as defined by solid-phase single-antigen (SA) assays for predicting long-term graft survival after kidney transplantation. Sera from 132 kidney transplant recipients were retrospectively tested before, 3, 6 and 12 months after transplantation. The incidence of rejection and graft survival was followed up for 7 years. We found 29 episodes of acute cellular rejection (CR), 21 cases of antibody-mediated rejection (AMR) and 18 graft failures due to immunological reasons. Pre-transplant DSA and DSA three months after transplantation correlated with an increased rate of AMR and impaired graft function. After the fourth year, recipients with persistent DSA were at a higher risk of graft failure (p = 0.0317). Antibody specificity was prevailingly to HLA class I antigens (66.6% DSA, 75% non-DSA). During the first year after transplantation, the number of patients with non-DSA decreased (30.3% to 10.7%), while, due to de novo production of antibodies, the number of DSA positive patients remained constant. Conclusion: Detection of antibodies to HLA antigens using solid-phase assays, especially single-antigen bead technology before and three months after transplantation is predictive for increased incidence of antibody-mediated rejection and impaired long-term kidney graft survival

Cytokine gene polymorphisms and high-resolution-computed tomography score in idiopathic pulmonary fibrosis

SummaryIntroductionIdiopathic pulmonary fibrosis (IPF) is a serious disease with unknown cause and the influence of cytokine gene polymorphisms is presumed in the etiology and pathogenesis of the disease. We used high-resolution computed tomography (HRCT) as a marker of disease stage and progression and compared the alveolar and interstitial score with IL-1, IL-4, IL-12, IL-1RA and IL-4RA cytokine gene polymorphisms.Subjects and methodsThe IPF patients were all Caucasians from the Czech Republic and consisted of 20 females and 10 males, with a mean age of 65 years, range 36–85. The HRCT results were evaluated by an experienced viewer using the interstitial and alveolar score scales, which were based on the IPF HRCT description system from Gay SE, Kazerooni EA, Tows GB, Lynch JP, Gross BH, Cascade PN, et al. [Idiopathic pulmonary fibrosis. Predicting response to therapy and survival. Am J Respir Crit Care Med 1998;157:1063–72]. We evaluated the polymorphisms of cytokine genes utilizing a PCR with sequence-specific primers method.ResultsThe HRCT alveolar score was more pronounced in IL-4 RA (+1902) AG heterozygotes. The HRCT interstitial score was less severe in the IL-12 (−1188) AA homozygotes. According to progression of the HRCT interstitial score, the CC homozygosity at IL-1 RA (mspa 111100), the AA homozygosity at IL-4 RA (+1902) and CC homozygosity at IL-4(+33) positions were more frequent in patients with stable disease compared to those with progressive disease.ConclusionsWe assume from our data that the polymorphisms of IL-4, IL-4RA, IL-1RA and IL-12 genes (genes of cytokines with regulatory activity) might influence the phenotype of IPF as shown by measurable changes in HRCT investigations

Safety and Immunogenicity of SARS-CoV-2 mRNA Vaccine Booster Doses in Kidney Transplant Recipients: Results of a 12-mo Follow-up From a Prospective Observational Study

Background. Booster doses of SARS-CoV-2 mRNA vaccines are commonly used in kidney transplant recipients (KTRs). However, there is uncertainty regarding the waning of vaccination responses and immunological safety in KTRs. Methods. A total of 123 KTRs were included in the final analysis of this prospective observational cohort study. The aim was to evaluate the immunogenicity and immunological safety. SARS-CoV-2 antispike IgG antibodies and anti-HLA antibodies were measured at baseline and then at months 3, 6, and 12 after vaccination with the first booster dose (ie, the third vaccine dose). Antibodies against S1 and S2 subunits of SARS-CoV-2 were evaluated using an immunochemiluminescent assay (cutoff 9.5 AU/mL, sensitivity 91.2%, and specificity 90.2%). Anti-HLA antibodies were analyzed using single-antigen bead technology. Results. Seroconversion was reached in 65% of KTRs previously nonresponding to 2-dose mRNA vaccination; the overall seroconversion rate 3 mo after the first booster dose was 83%. Vaccination induced a durable humoral response, and the antibody levels were stable during the 12-mo study follow-up. Higher age (exponentiated beta coefficient [eβ] 0.97; 95% confidence interval [CI], 0.943-0.997) and a full dose of mycophenolate (eβ 0.296; 95% CI, 0.089-0.984) were negatively associated with SARS-CoV-2 IgG antibody levels, whereas better graft function (eβ1.021; 95% CI, 1.005-1.037) was associated positively. There were no systematic signs of anti-HLA antibody development after vaccination. However, during the follow-up, there was a nonsignificant signal of an increase in anti-HLA antibodies in those who developed COVID-19. Conclusions. Additional booster doses of SARS-CoV-2 mRNA vaccines induce durable antibody response even in a large subset of previous nonresponders and are not associated with the risk of allosensitization. Furthermore, a signal linking COVID-19 to the development of anti-HLA antibodies was observed, and this should be confirmed and further examined (NCT05483725)

Data and Optimization Requirements for Kidney Exchange Programs

Kidney Exchange Programs (KEP) are valuable tools to increase the options of living donor kidney transplantation for patients with end-stage kidney disease with an immunologically incompatible live donor. Maximising the benefits of a KEP requires an information system to manage data and to optimise transplants. The data input specifications of the systems that relate to key information on blood group and Human Leukocyte Antigen (HLA) types and HLA antibodies are crucial in order to maximise the number of identified matched pairs while minimising the risk of match failures due to unanticipated positive crossmatches. Based on a survey of eight national and one transnational kidney exchange program, we discuss data requirements for running a KEP. We note large variations in the data recorded by different KEPs, reflecting varying medical practices. Furthermore, we describe how the information system supports decision making throughout these kidney exchange programs

The HLA-net GENE[RATE] pipeline for effective HLA data analysis and its application to 145 population samples from Europe and neighbouring areas

In this review, we present for the first time an integrated version of the Gene[rate] computer tools which have been developed during the last 5 years to analyse human leukocyte antigen (HLA) data in human populations, as well as the results of their application to a large dataset of 145 HLA-typed population samples from Europe and its two neighbouring areas, North Africa and West Asia, now forming part of the Gene[va] database. All these computer tools and genetic data are, from now, publicly available through a newly designed bioinformatics platform, HLA-net, here presented as a main achievement of the HLA-NET scientific programme. The Gene[rate] pipeline offers user-friendly computer tools to estimate allele and haplotype frequencies, to test Hardy-Weinberg equilibrium (HWE), selective neutrality and linkage disequilibrium, to recode HLA data, to convert file formats, to display population frequencies of chosen alleles and haplotypes in selected geographic regions, and to perform genetic comparisons among chosen sets of population samples, including new data provided by the user. Both numerical and graphical outputs are generated, the latter being highly explicit and of publication quality. All these analyses can be performed on the pipeline after scrupulous validation of the population sample's characterisation and HLA typing reporting according to HLA-NET recommendations. The Gene[va] database offers direct access to the HLA-A, -B, -C, -DQA1, -DQB1, -DRB1 and -DPB1 frequencies and summary statistics of 145 population samples having successfully passed these HLA-NET 'filters', and representing three European subregions (South-East, North-East and Central-West Europe) and two neighbouring areas (North Africa, as far as Sudan, and West Asia, as far as South India). The analysis of these data, summarized in this review, shows a substantial genetic variation at the regional level in this continental area. These results have main implications for population genetics, transplantation and epidemiological studies. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd 83 5 May 2014 10.1111/tan.12356 Review article Review article © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.SCOPUS: re.jinfo:eu-repo/semantics/publishe