RESUMEN
Cytomegalovirus (CMV) infection is the most frequent infection episode in kidney transplant (KT) recipients. Reactivation usually occurs in the first three months after transplantation and is associated with higher cellular and/or antibody-mediated rejection rates and poorer graft performance. CMV induces the expression of BAFF (B-cell-activating factor, a cytokine involved in the homeostasis of B cells), which communicates signals for survival and growth to B cells and virus-specific plasma cells via the R-BAFF (BAFF receptor), TACI (the calcium modulator, the cyclophilin ligand interactor), and BCMA (B cell maturation antigen) receptors. These molecules of the BAFF system have also been suggested as biomarkers for the development of alloantibodies and graft dysfunction. This prospective study included 30 CMV-IgG seropositive KT recipients. The expression levels of the genes BAFF-R, transmembrane activator and CAML interactor (TACI), and B cell maturation antigen (BCMA) in peripheral blood leukocytes (PBL) pre-KT were determined using qPCR. qPCR was also used to monitor CMV reactivation in the first three months following KT. The remainder of the KT recipients were classified as CMV- reactivation, and those with more than 500 copies/mL in at least one sample were classified as CMV+ reactivation. There were no discernible variations in the BAFF-R and TACI transcript expression levels. In the CMV+ group, we examined the relationship between the transcript levels and peak viremia. Peak viremia levels and BCMA transcript levels showed a strong correlation. BAFF-R and TACI expressions showed no measurable differences. In patients with early CMV reactivation, high BCMA receptor expression was associated with increased plasmablast, lymphocyte B cell class-switched levels (LBCS), and viral load. Our findings demonstrate that pre-KT BCMA transcript levels increased in KT recipients with early CMV reactivation. These transcript levels positively correlate with peak viremia and weakly with plasmablast and LBCS levels in PBLs.
Asunto(s)
Antígeno de Maduración de Linfocitos B , Citomegalovirus , Humanos , Antígeno de Maduración de Linfocitos B/genética , Antígeno de Maduración de Linfocitos B/metabolismo , Estudios Prospectivos , Viremia , Proteína Activadora Transmembrana y Interactiva del CAML/genética , Factor Activador de Células B/genética , Inmunoglobulina GRESUMEN
HLA-DPA1*02:134, a novel HLA class II allele detected by next-generation sequencing.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Cadenas alfa de HLA-DP/genética , Prueba de Histocompatibilidad/métodos , CodónRESUMEN
HLA-DQA1*05:03:03, a novel HLA class II allele detected by next-generation sequencing.
Asunto(s)
Alelos , Exones , Cadenas alfa de HLA-DQ , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Cadenas alfa de HLA-DQ/genética , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Prueba de Histocompatibilidad/métodos , Codón , Secuencia de Bases , Análisis de Secuencia de ADN/métodosRESUMEN
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity pulmonary disease that affects both patients with cystic fibrosis (CF) and those with asthma. HLA-DRB1 alleles have previously been associated with ABPA-CF susceptibility; however, HLA-DQB1 allele associations have not been clearly established. The aim of the present study was to investigate HLA class II associations in patients with ABPA-CF and determine their roles in susceptibility or protection. Patients with ABPA-CF, patients with CF without ABPA, patients with asthma without ABPA (AST), and healthy controls were included in this study. DNA was extracted by automatic extractor. HLA-DRB1 and -DQB1 genotyping was performed by the Luminex PCR-SSOP method (One Lambda, Canoga Park, CA, USA). Allele specific PCR-SSP was also performed by high-resolution analysis (One Lambda). Statistical analysis was performed with SSPS and Arlequin software. Both HLA-DRB1*5:01 and -DRB1*11:04 alleles occurred with greater frequency in patients with ABPA-CF than in those with AST and CF and control subjects, corroborating previously published data. On the other hand, analysis of haplotypes revealed that almost all patients with ABPA-CF lacking DRB1*15:01 or DRB1*11:04 carry either DRB1*04, DRB1*11:01, or DRB1*07:01 alleles. In the HLA-DQB1 region, the HLA-DQB1*06:02 allele occurred more frequently in patients with ABPA-CF than in those with AST and CF and healthy controls, whereas HLA-DQB1*02:01 occurred less frequently in patients with ABPA-CF. These data confirm that there is a correlation between HLA-DRB1*15:01, -DRB1*11:04, DRB1*11:01, -DRB1*04 and -DRB1*07:01 alleles and ABPA-CF susceptibility and suggest that HLA-DQB1*02:01 is an ABPA-CF resistance allele.
Asunto(s)
Aspergilosis Broncopulmonar Alérgica/genética , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ/genética , Cadenas HLA-DRB1/genética , Fibrosis Quística/complicaciones , Frecuencia de los Genes , Genotipo , Humanos , Reacción en Cadena de la PolimerasaRESUMEN
HLA-B*35:572 and HLA-C*04:491, two novel HLA class I alleles detected by next-generation sequencing.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Antígenos HLA-B/genética , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Five novel HLA-DQB1 intronic variants detected by next-generation sequencing: HLA-DQB1* 03:01:01:53, -DQB1*03:01:01:55, -DQB1*03:02:01:17, -DQB1*03:02:01:18 and - DQB1*06:03:01:20.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Cadenas beta de HLA-DQ/genética , IntronesRESUMEN
HLA-DPB1*1443:01 and -DPB1*11:01:07, two novel HLA-DPB1 alleles detected by next generation sequencing.
Asunto(s)
Cadenas beta de HLA-DP , Humanos , Cadenas beta de HLA-DP/genética , Alelos , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
Characterization of three new HLA class I alleles, HLA-A*02:1008, -A*24:553 and -C*12:350, identified in Spanish hematopoietic stem cell donors.
Asunto(s)
Células Madre Hematopoyéticas , Donantes de Tejidos , Humanos , Alelos , Prueba de Histocompatibilidad , Antígenos HLA-A/genéticaRESUMEN
HLA-DPA1*02:102Q, a novel HLA class II allele detected by next-generation sequencing.
Asunto(s)
Cadenas alfa de HLA-DP , Humanos , Alelos , Cadenas alfa de HLA-DP/genéticaRESUMEN
BACKGROUND: T cells play a fundamental role in the processes that mediate graft rejection, tolerance, and defense against infections. The CXCR3 and CCR6 receptors, highly expressed in Th1 (type 1 T helper cells)/Tc1 (T cytotoxic cells, type 1), Th1-Tc1, and Th17-Tc17 lymphocytes, respectively, participate in cell migration toward inflamed tissues. The altered expression level of CXCR3 and CCR6 has been associated with different clinical events after renal transplantation, such as acute rejection (AR) and chronic graft dysfunction, but data are still limited. In this study, we evaluated the expression of the receptor CXCR3 and CCR6 in peripheral blood T lymphocytes from kidney transplant recipients (KTR) and their association with viral infections, AR, and allograft function. METHODS: Through flow cytometry, the peripheral blood expression of CXCR3 and CCR6 in T cells was evaluated in a pretransplant collection of KTR. The levels of these T subpopulations and their association with the incidence of AR, kidney graft function, viral infections, cytomegalovirus, and BK virus were studied. Adverse clinical events and graft function were monitored during the first year post transplant. RESULTS: KTRs with low pretransplantation levels of Th17 (CD4+CXCR3-CCR6+) (tertile 1, Th17<16.4%) had a higher risk of suffering AR during the first year post transplantation (P = .033). KTRs with viral infections or reactivations during the first 3 months post transplantation had significantly lower levels of Tc17 (CD8+CXCR3-CCR6+) and higher levels of Th1 (CD4+CXCR3+CCR6-). In patients with cytomegalovirus reactivations, the viral peak correlates negatively with the pretransplant levels of Th1 (r = -0.606, P = .037). CONCLUSIONS: Pretransplantation assessment of Th1-Th17 and Tc1-Tc17 levels may help predict post-transplant clinical events such as AR and reactivation of viral infections.
Asunto(s)
Trasplante de Riñón , Receptores CCR6 , Receptores CXCR3 , Células TH1 , Receptores de Trasplantes , Humanos , Relevancia Clínica , Riñón/metabolismo , Trasplante de Riñón/efectos adversos , Receptores CCR6/metabolismo , Células Th17 , Trasplante HomólogoRESUMEN
In kidney transplantation, a biopsy is currently the gold standard for monitoring the transplanted organ. However, this is far from an ideal screening method given its invasive nature and the discomfort it can cause the patient. Large-scale studies in renal transplantation show that approximately 1% of biopsies generate major complications, with a risk of macroscopic hematuria greater than 3.5%. It would not be until 2011 that a method to detect donor-derived cell-free DNA (dd-cfDNA) employing digital PCR was devised based on analyzing the differences in SNPs between the donor and recipient. In addition, since the initial validation studies were carried out at the specific moments in which rejection was suspected, there is still not a good understanding of how dd-cfDNA levels naturally evolve post-transplant. In addition, various factors, both in the recipient and the donor, can influence dd-cfDNA levels and cause increases in the levels of dd-cfDNA themselves without suspicion of rejection. All that glitters in this technology is not gold; therefore, in this article, we discuss the current state of clinical studies, the benefits, and disadvantages.
RESUMEN
Alpha-1 antitrypsin (AAT1) deficiency (AAT1D) is an inherited disease with an increased risk of chronic obstructive pulmonary disease (COPD), liver disease, and skin and blood vessel problems. AAT1D is caused by mutations in the SERPINE1 gene (Serine Protease Inhibitor, group A, member 1). Numerous variants of this gene, the Pi system, have been identified. The most frequent allelic variants are Pi*M, Pi*S, and Pi*Z. The development of COPD requires both a genetic predisposition and the contribution of an environmental factor, smoking being the most important. Studies on this deficiency worldwide are very scarce, and it is currently considered a rare disease because it is underdiagnosed. The aim of this study was to analyze the genotypic frequencies of mutations associated with AAT1 deficiency in unrelated bone marrow donors from the donor registry of the Region of Murcia in southeastern Spain due to the high risk of presenting with different pathologies and underdiagnosis in the population. A total of 112 DNA-healthy voluntary unrelated bone marrow donors from different parts of the Region of Murcia were analyzed retrospectively. AAT1 deficiency patient testing involved an automated biochemical screening routine. The three main variants, Pi*M, Pi*Z, and Pi*S, were analyzed in the SERPINE1 gene. Our results showed a frequency of 3.12% of the Pi*Z (K342) mutation in over 224 alleles tested in the healthy population. The frequency of Pi*S (V264) was 11.1%. The frequency of the haplotype with the most dangerous mutation, EK342 EE264, was 4.46%, and the frequency of EK342 EV264 was 1.78% in the healthy population. Frequencies of other EE342 EV264-mutated haplotypes accounted for 18.7%. As for the EE342 VV264 haplotype, 0.89% of the total healthy population presented heterozygous for the EV264 mutation and one individual presented homozygous for the VV264 mutation. In conclusion, the frequencies of Pi mutations in the healthy population of the Region of Murcia were not remarkably different from the few studies reported in Spain. The genotype and haplotype frequencies followed the usual pattern. Health authorities should be aware of this high prevalence of the Pi*S allelic variant and pathological genotypes such as Pi*MZ and Pi*SZ in the healthy population if they consider screening the smoking population.
RESUMEN
BAFF system plays an essential role in B cells homeostasis and tolerance, although it has widely not been tested in transplantation with doubtful results. The main purpose was to study the BAFF soluble forms and their correlation with acute rejection (AR) and donor-specific antibodies production. Serum levels of BAFF, APRIL, and soluble forms of their receptors were analyzed in renal recipients with and without acute rejection (AR/NAR) appearance. All molecules were evaluated at pre- and post-transplantation. sTACI showed a significant correlation with BAFF and sR-BAFF levels, and sBCMA also showed a positive correlation with sAPRIL levels. A significant increase in sAPRIL levels in patients suffering AR was also found, and ROC curves analysis showed an AUC = 0.724, a concentration of 6.05 ng/ml (sensitivity: 66.7%; specificity: 73.3%), the best cutoff point for predicting AR. In the post-transplant dynamics of sAPRIL levels in the longitudinal cohort, we observed a significant decrease at 3 and 6 month post-transplantation compared to pretransplantation status. We also observed that recipients with high pre-transplant levels of sAPRIL generated antibodies earlier than those with lower sAPRIL levels, although their long-term post-transplantation was not different. Our results show that elevated serum levels of APRIL may be helpful as a biomarker for the diagnosis of AR, although the longitudinal study shows that it is not helpful as a prognostic biomarker.
Asunto(s)
Trasplante de Riñón , Factor Activador de Células B , Biomarcadores , Rechazo de Injerto , Humanos , Estudios Longitudinales , Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis TumoralRESUMEN
B-cell activating factor (BAFF) system signaling is critical for B-cell homeostasis, effector functions, and tolerance maintenance in transplants, but it has not been studied in kidney transplant recipients (KTRs). The aim was to analyze the changes in BAFF system expression in KTRs with/without acute rejection (AR/NAR). The BAFF system expression was analyzed by qPCR in 40 KTRs. A meta-analysis of BAFF system expression and histological renal damage was identified by the Chronic Allograft Damage Index (CADI) and performed from the GEO database. Proliferation-inducing ligand (APRIL) expression increased at three- and six-months post-KT (p = 0.014 and p < 0.001). B-cell maturation antigen (BCMA) expression increased at six-months post-KT (p = 0.038). BAFF expression remained stable in NAR-KTRs, but was increased in CADI concerning the No-CADI group at one year (p = 0.008). BCMA expression increased in the CADI group at one- (p = 0.001) and six-years post-KT (p = 0.024). At three months, the transmembrane activator and calcium modulator interactor (TACI) gene significantly elevated KTRs with DSAs (donor-specific antibody; p = 0.034). KTRs with DSAs significantly increase the B-cell activating factor receptor (R-BAFF; p = 0.021) and TACI (p = 0.018) between pre- and three-month post-KT. Changes in the expression of the BAFF system increase during post-KTR in the development of AR and chronic allograft damage, and could be an important pathological tool to detect and prevent kidney graft outcomes.
RESUMEN
Background: The diagnosis of graft rejection in kidney transplantation (KT) patients is made by evaluating the histological characteristics of biopsy samples. The evolution of omics sciences and bioinformatics techniques has contributed to the advancement in searching and predicting biomarkers, pathways, and new target drugs that allow a more precise and less invasive diagnosis. The aim was to search for differentially expressed genes (DEGs) in patients with/without antibody-mediated rejection (AMR) and find essential cells involved in AMR, new target drugs, protein-protein interactions (PPI), and know their functional and biological analysis. Material and Methods: Four GEO databases of kidney biopsies of kidney transplantation with/without AMR were analyzed. The infiltrating leukocyte populations in the graft, new target drugs, protein-protein interactions (PPI), functional and biological analysis were studied by different bioinformatics tools. Results: Our results show DEGs and the infiltrating leukocyte populations in the graft. There is an increase in the expression of genes related to different stages of the activation of the immune system, antigenic presentation such as antibody-mediated cytotoxicity, or leukocyte migration during AMR. The importance of the IRF/STAT1 pathways of response to IFN in controlling the expression of genes related to humoral rejection. The genes of this biological pathway were postulated as potential therapeutic targets and biomarkers of AMR. These biological processes correlated showed the infiltration of NK cells and monocytes towards the allograft. Besides the increase in dendritic cell maturation, it plays a central role in mediating the damage suffered by the graft during AMR. Computational approaches to the search for new therapeutic uses of approved target drugs also showed that imatinib might theoretically be helpful in KT for the prevention and/or treatment of AMR. Conclusion: Our results suggest the importance of the IRF/STAT1 pathways in humoral kidney rejection. NK cells and monocytes in graft damage have an essential role during rejection, and imatinib improves KT outcomes. Our results will have to be validated for the potential use of overexpressed genes as rejection biomarkers that can be used as diagnostic and prognostic markers and as therapeutic targets to avoid graft rejection in patients undergoing kidney transplantation.
Asunto(s)
Biología Computacional , Rechazo de Injerto/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Leucocitos/efectos de los fármacos , Proteoma , Transcriptoma , Biomarcadores/metabolismo , Bases de Datos Genéticas , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , Rechazo de Injerto/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/metabolismo , Humanos , Inmunidad Humoral/efectos de los fármacos , Factores Reguladores del Interferón/genética , Factores Reguladores del Interferón/metabolismo , Leucocitos/inmunología , Leucocitos/metabolismo , Terapia Molecular Dirigida , Fenotipo , Mapas de Interacción de Proteínas , Proteómica , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: The kidney allograft biopsy is considered the gold standard for rejection diagnosis but is invasive and could be indeterminate. Several publications point to the role of miRNA expression in suggesting its involvement in the acceptance or rejection of organ transplantation. This study aimed to analyze microRNAs involved in the differentiation and activation of B and T lymphocytes from kidney transplant (KT) patients' peripheral blood leukocytes to be used as biomarkers of acute renal rejection (AR). METHODS: A total of 15 KT patients with and without acute rejection (AR/NAR) were analyzed and quantified by miRNA PCR array. A total of 84 miRNAs related to lymphocyte differentiation and activation B and T were studied. The functions and biological pathways were analyzed to predict the potential targets of differential expressed miRNAs. RESULTS: Six miRNA were increased in the AR group (miR-191-5p, miR-223-3p, miR-346, miR-423-5p, miR-574-3p, and miR-181d) and miR-150-5p was increased in the NAR group. In silico studies showed a total of 2603 target genes for the increased miRNAs in AR, while for the decrease miRNA, a total of 1107 target-potential genes were found. CONCLUSIONS: Our results show that KT with AR shows a decrease in miR-150-5p expression compared to NAR, suggesting that the decrease in miR-150-5p could be related to an increased MBD6 whose deregulation could have clinical consequences.
RESUMEN
BACKGROUND: B lymphocytes (BL) seem to play an important role in transplantation, although the and role of different subpopulations in monitoring and outcome is not clear. Our aim was to monitoring immunological profiles based on BL subpopulations in kidney recipients (KR) with the risk of acute rejection (AR). METHODS: Monitoring of BL subpopulations was performed by flow cytometry in PBLs before transplantation and three and six months after transplantation (PTX). We used two methodological approaches, a traditional analysis, and a novel cluster analysis, to determine the association between BL subpopulations, AR incidence, and graft function. RESULTS: After three months of PTX, KRs with a B phenotype enriched in transitional BL and plasmablasts had better kidney function and lower AR incidence. KRs with decreased transitional BL and plasmablasts were associated with lower kidney function and higher AR PTX. KRs that had an increase in transitional BL PTX had a better clinical outcome. The increase in transitory BL during PTX was also associated with an increase in Tregs. Indeed, KRs receiving thymoglobulin as induction therapy showed a slight decrease in the relative frequency of naive BLs after three months of PTX. CONCLUSION: The monitoring of BL subpopulations may serve as a non-invasive tool to improve immunological follow-up of patients after kidney transplantation. However, further studies are needed to confirm the obtained results, define cut-off values, and standardize more optimal and even custom/customized protocols.
RESUMEN
Kidney transplantation (KT) clinical outcomes are highly variable across patients and would benefit from predictive biomarkers to achieve personalized/precision medicine. The B cell activating factor (BAFF) system signaling plays an essential role in B lymphocytes' homeostasis, and is implicated in activation and survival of B lymphocytes. Single nucleotide polymorphisms (SNPs) in BAFF system genes are therefore strong candidates to identify the genetic mechanisms underpinning variable clinical outcomes in KT. We report here new findings on BAFF system genetic polymorphisms in KT patients in relation to two key phenotypes of clinical interest: graft survival and acute rejection (AR). A total of 168 KT patients, of which 29 suffered AR, participated in this study. The BAFF system polymorphisms in five genes TNFSF13B, TNFSF13, TNFRSF13C, TNFRSF13B, and TNFRSF17 were characterized using TaqMan SNP genotyping. Patients with KT who had an AA genotype in polymorphism rs3803800 of the TNFSF13 gene had a higher risk of suffering AR (p = 0.046; odds ratios = 3.38, 95% CI: 1.02-11.2). Moreover, patients with AA genotype (rs3803800) in the TNFSF13 gene had a significantly lower AR-free time than the GG/GA genotypes (69.2% vs. 85.7%; p = 0.037). Of importance, bioinformatics analysis showed that the polymorphism rs3803800 could alter splicing regulation and affect the proliferation-inducing ligand (APRIL) expression levels. The analysis of graft survival did not show a significant association with the polymorphisms analyzed in this study. In conclusion, the rs3803800 genetic polymorphism from this study of BAFF system genes appears to display importance in AR-free time for KT patients, and thus, warrants further research in independent populations as a putative predictive biomarker of AR. These findings also inform future personalized/precision medicine efforts and functional genomic studies in KT patients.
Asunto(s)
Trasplante de Riñón , Medicina de Precisión , Factor Activador de Células B/genética , Rechazo de Injerto/genética , Supervivencia de Injerto/genética , Humanos , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Background: Antibody-mediated rejection (AMR) is the major cause of kidney transplant rejection. The donor-specific human leukocyte antigen (HLA) antibody (DSA) response to a renal allograft is not fully understood yet. mTOR complex has been described in the accommodation or rejection of transplants and integrates responses from a wide variety of signals. The aim of this study was to analyze the expression of the mTOR pathway genes in a large cohort of kidney transplant patients to determine its possible influence on the transplant outcome. Methods: A total of 269 kidney transplant patients monitored for DSA were studied. The patients were divided into two groups, one with recipients that had transplant rejection (+DSA/+AMR) and a second group of recipients without rejection (+DSA/-AMR and -DSA/-AMR, controls). Total RNA was extracted from kidney biopsies and reverse transcribed to cDNA. Human mTOR-PCR array technology was used to determine the expression of 84 mTOR pathway genes. STRING and REVIGO software were used to simulate gene to gene interaction and to assign a molecular function. Results: The studied groups showed a different expression of the mTOR pathway related genes. Recipients that had transplant rejection showed an over-expressed transcript (≥5-fold) of AKT1S1, DDIT4, EIF4E, HRAS, IGF1, INS, IRS1, PIK3CD, PIK3CG, PRKAG3, PRKCB (>12-fold), PRKCG, RPS6KA2, TELO2, ULK1, and VEGFC, compared with patients that did not have rejection. AKT1S1 transcripts were more expressed in +DSA/-AMR biopsies compared with +DSA/+AMR. The main molecular functions of up-regulated gene products were phosphotransferase activity, insulin-like grown factor receptor and ribonucleoside phosphate binding. The group of patients with transplant rejection also showed an under-expressed transcript (≥5-fold) of VEGFA (>15-fold), RPS6, and RHOA compared with the group without rejection. The molecular function of down-regulated gene products such as protein kinase activity and carbohydrate derivative binding proteins was also analyzed. Conclusions: We have found a higher number of over-expressed mTOR pathway genes than under-expressed ones in biopsies from rejected kidney transplants (+DSA/+AMR) with respect to controls. In addition to this, the molecular function of both types of transcripts (over/under expressed) is different. Therefore, further studies are needed to determine if variations in gene expression profiles can act as predictors of graft loss, and a better understanding of the mechanisms of action of the involved proteins would be necessary.
RESUMEN
AIM: To validate intracellular cytokine production functional assay as means of cell-mediated immunity monitoring of post-transplant patients with opportunistic infection (OI). METHODS: Intracellular cytokine-producing CD4+ and CD8+ T-cell monitoring was carried out in 30 liver transplant (LTr) and 31 kidney transplant (KTr) recipients from 2010 to 2012. Patients were assessed in our Department of Immunology at the Clinical University 'Hospital Virgen de la Arrixaca-IMIB' in Murcia, Spain for one year following transplantation. FACS Canto II flow cytometer was employed to quantify the intracellular production of IL-17, IFNγ and IL-10 cytokines on stimulated CD4+CD69+ and CD8+CD69+ T cells and BD FACS DIVA v.6 software was used to analysed the data. Statistical analysis was carried out using SPSS 22.0. RESULTS: LTr with OI had significantly lower % of CD8+CD69+IFNγ+ T cells at 60 (7.95 ± 0.77 vs 26.25 ± 2.09, P < 0.001), 90 (7.47 ± 1.05 vs 30.34 ± 3.52, P < 0.001) and 180 (15.31 ± 3.24 vs 24.59 ± 3.28, P = 0.01) d post-transplantation. Higher % of CD4+CD69+IL-10+ as well as CD4+CD69+IL-17+ T cells were yet reported at 30 (14.06 ± 1.65 vs 6.09 ± 0.53, P = 0.0007 and 4.23 ± 0.56 vs 0.81 ± 0.14, P = 0.005; respectively), 60 (11.46 ± 1.42 vs 4.54 ± 0.91, P = 0.001 and 4.21 ± 0.59 vs 1.43 ± 0.42, P = 0.03; respectively) and 90 d (16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 3.97 ± 0.43 vs 0.96 ± 0.17, P = 0.001). Yet, KTr with OI had significantly lower percentage of CD4+CD69+IFNγ+ at 30 (11.80 ± 1.59 vs 20.64 ± 3.26, P = 0.035), 60 (11.19 ± 1.35 vs 15.85 ± 1.58, P = 0.02), 90 (11.37 ± 1.42 vs 22.99 ± 4.12, P = 0.028) and 180 (13.63 ± 2.21 vs 21.93 ± 3.88, P = 0.008) d post-transplantation as opposed to CD4+CD69+IL-10+ and CD8+CD69+IL-10+ T cells which percentages were higher at 30 (25.21 ± 2.74 vs 8.54 ± 1.64, P < 0.001 and 22.37 ± 1.35 vs 17.18 ± 3.54, P = 0.032; respectively), 90 (16.85 ± 1.60 vs 4.07 ± 0.63, P < 0.001 and 23.06 ± 2.89 vs 10.19 ± 1.98, P = 0.002) and 180 (21.81 ± 1.72 vs 6.07 ± 0.98, P < 0.001 and 19.68 ± 2.27 vs 10.59 ± 3.17, P = 0.016) d post-transplantation. The auROC curve model determined the most accurate cut-off values to stratify LTr and KTr at high risk of OI and Cox Regression model confirmed these biomarkers as the most significant risk factors to opportunistic infection. CONCLUSION: Post-transplant percentages of T-cell subsets differed significantly amongst infected- and non-infected-LTr and -KTr and yet this imbalance was found to contribute towards a worst clinical outcome.