Changes in phenotypic patterns of blood monocytes after kidney transplantation and during acute rejection.

Peripheral blood monocytes, which serve as precursors for tissue macrophages and dendritic cells (DC), play a key role in the immune response to kidney allograft, reparation processes and homeostasis regulation. In this prospective study, we used multicolor flow cytometry to monitor the phenotypic patterns of peripheral monocytes in subjects with uncomplicated outcomes and those with acute rejection. We found a reciprocal increase in the proportion of "classical monocytes" (CD14+CD16-) along with a decline in pro-inflammatory "intermediary" (CD14+CD16+) and "non-classical" (CD14lowCD16+) monocytes in subjects with normal outcomes. In subjects with acute rejection, we observed no reduction in "intermediary" monocytes and no increase in "classical" monocytes. Patients with uncomplicated outcomes exhibited downregulated HLA-DR in all three monocyte subpopulations. However, non-classical monocytes were unaffected in subjects with acute rejection. Expression of CD47 was downregulated after transplantation, while patients with antibody-mediated rejection and donor-specific antibodies showed higher pre-transplant values. In monocytes isolated at the time of biopsy, CD47 expression was higher in individuals with acute rejection compared to patients with normal outcomes one year post-transplant. Expression of CD209 (DC-SIGN) and the proportion of CD163+CD206+ subpopulations were upregulated during the first week after kidney transplantation. CD209 was also upregulated in samples taken on the day of biopsy confirming acute rejection. Our data demonstrate that kidney allograft transplantation is associated with phenotypic changes in peripheral blood monocytes during acute rejection.

The effect of induction therapy on established CMV specific T cell immunity in living donor kidney transplantation.

Cytomegalovirus (CMV) infection influences both short and long term outcomes in immunosuppressed organ transplant recipients. The aim of this study was to evaluate the effect of different induction immunosuppression regimens on CMV specific T cell response in patients with already established CMV immunity. In 24 seropositive living donor kidney recipients, the frequency of CMV specific T cells was determined by ELISPOT (Enzyme-Linked ImmunoSpot) assay prior and 6 months after transplantation. Recipients' peripheral blood mononuclear cells were stimulated with immediate-early (IE1) and phosphoprotein 65 (pp65) CMV-derived peptide pools and the number of cells producing interferon gamma (IFN-gamma) was assessed. Patients received quadruple immunosuppression based either on depletive rabbit antithymocyte globulin (rATG) or non-depletive basiliximab induction and tacrolimus/mycophenolate mofetil/steroids. Patients with rATG induction received valgancyclovir prophylaxis. No effects of different induction agents on CMV specific T cell immunity were found at sixth month after kidney transplantation. There were no associations among dialysis vintage, pretransplant CMV specific T cell immunity, and later CMV DNAemia. Similarly, no effect of CMV prophylaxis on CMV specific T cell immunity was revealed. This study shows no effect of posttransplant immunosuppression on CMV specific T cell immunity in living donor kidney transplant recipients with CMV immunity already established, regardless of lymphocyte depletion and CMV prophylaxis.

Safety and Efficacy of Immunoadsorption in Heart Transplantation Program.

BACKGROUND: Antibody-mediated rejection (AMR) is a serious complication of organ transplantation, and its treatment is complex. The aim of this study was to assess immunoadsorption (IA) for treatment-immunized patients before heart transplantation (HTX) and as the first step of AMR treatment after HTX. METHODS: The cohort consisted of 10 patients (8 men, 2 women; age range, 20-57 years). For 3 of these patients, IA was included in the desensitization protocol before HTX; for 7 patients, IA was the first step of the treatment protocol. One patient underwent IA before and after HTX. RESULTS: A comparison of values before IA and after the last procedure showed a decrease in immunoglobulin subgroups (G, M, and A). In patients before HTX, a decline was noted in panel reactive antibodies. After HTX, IA procedures led to a significant decrease in donor-specific antibody (DSA) class I; DSA class II fell in 6 of 7 patients, with 51% falling below the detection limit. CONCLUSIONS: IA in patients during HTX is safe procedure for reducing DSA. The removal of antibodies is the first step in comprehensive treatment and must be followed by a procedure that prevents their further development.

16(th) IHIW: analysis of HLA population data, with updated results for 1996 to 2012 workshop data (AHPD project report).

We present here the results of the Analysis of HLA Population Data (AHPD) project of the 16th International HLA and Immunogenetics Workshop (16IHIW) held in Liverpool in May-June 2012. Thanks to the collaboration of 25 laboratories from 18 different countries, HLA genotypic data for 59 new population samples (either well-defined populations or donor registry samples) were gathered and 55 were analysed statistically following HLA-NET recommendations. The new data included, among others, large sets of well-defined populations from north-east Europe and West Asia, as well as many donor registry data from European countries. The Gene[rate] computer tools were combined to create a Gene[rate] computer pipeline to automatically (i) estimate allele frequencies by an expectation-maximization algorithm accommodating ambiguities, (ii) estimate heterozygosity, (iii) test for Hardy-Weinberg equilibrium (HWE), (iv) test for selective neutrality, (v) generate frequency graphs and summary statistics for each sample at each locus and (vi) plot multidimensional scaling (MDS) analyses comparing the new samples with previous IHIW data. Intrapopulation analyses show that HWE is rarely rejected, while neutrality tests often indicate a significant excess of heterozygotes compared with neutral expectations. The comparison of the 16IHIW AHPD data with data collected during previous workshops (12th-15th) shows that geography is an excellent predictor of HLA genetic differentiations for HLA-A, -B and -DRB1 loci but not for HLA-DQ, whose patterns are probably more influenced by natural selection. In Europe, HLA genetic variation clearly follows a north to south-east axis despite a low level of differentiation between European, North African and West Asian populations. Pacific populations are genetically close to Austronesian-speaking South-East Asian and Taiwanese populations, in agreement with current theories on the peopling of Oceania. Thanks to this project, HLA genetic variation is more clearly defined worldwide and better interpreted in relation to human peopling history and HLA molecular evolution.

Prediction of organ transplant rejection by HLA-specific and non-HLA antibodies--brief literature review.

The application of solid-phase assays for detection and definition of Human leucocyte antigen (HLA)-specific antibodies has significantly facilitated the diagnosis and monitoring of treatment of antibody-mediated rejection (AMR). There is, however, a major discussion in the literature concerning the clinical relevance of the use of the Luminex technique for the prediction of cellular and/or AMR and survival. This may be explained on one hand by the complexities of the method and on the other by variations in patient demographic characteristics, immunosuppression and other factors. As far as non-HLA antibodies, it is clear that they may induce AMR; nevertheless, a difficult problem in their definition remains the fact that most of the non-HLA antigens still remain to be identified. Hereby is a short literature review of several recent publications discussing the role of HLA- and non-HLA-specific antibodies in organ transplant rejection and survival.

Epithelial cells modulate genes associated with NF kappa B activation in co-cultured human macrophages.

Macrophages located in airways and the alveolar space are continually exposed to different signals from the respiratory mucosa. In this respect, epithelial cells represent an important source of cytokines and mediators modulating the state of activation and/or differentiation of mononuclear phagocytes. Many of the proinflammatory genes induced in macrophages during immune and immunopathological reactions are regulated by transcription factor NF kappa B. The aim of our study was to characterize changes in the expression of genes associated with NF kappa B activation and signalling in THP-1 human macrophages co-cultured with A549 respiratory epithelial cells. At least 4-fold upregulation of mRNA level was found in 29 of 84 tested genes including genes for multiple cytokines and chemokines, membrane antigens and receptors, and molecules associated with NF kappa B signalling. The mRNA induction was confirmed at the level of protein expression by evaluating the release of IL-6 and IL-8 and by ICAM-1 expression. Blocking of one NFκB subunit by p65 siRNA inhibited the production of IL-6 in both cell types while IL-8 release from THP-1 cells did not seem to be affected. We conclude from our data that unstimulated respiratory epithelial cells regulate genes associated with NF kappa B dependent immune responses in human macrophages and that these interactions may play a key role in immediate responses in the respiratory mucosa.

Th1/Th2 cytokine gene polymorphisms in patients with uterine fibroid.

Uterine fibroid or leiomyoma is a frequent non-malignant tumour with unknown aetiology and pathogenesis. The aim of our study was to look for possible genetic markers which could be used as prognostic tools for evaluation of an increased risk for development of uterine fibroid. A large spectrum of Th1/Th2 cytokine gene polymorphisms in 102 patients with uterine leiomyoma was compared with 145 healthy controls. An association between polymorphisms of the IL4 gene promotor at positions -590 C/T and -33 C/T, and the risk of leiomyoma was observed. The CC genotype of IL4 -590 and at position -33 was less frequent in the patient group than in the control group (P = 0.03). Besides IL-4, we observed different genotype distribution of the TNFA gene -308 A/G. The frequency of genotype AA was higher in the younger (≤ 35 years) patient group (P = 0.02). Our study thus suggests that certain cytokine gene polymorphisms, especially of the IL4 and TNFA genes, may be associated with increased risk for development of uterine fibroid. Further investigation would be needed to elucidate the mechanisms responsible for these associations.

Cytokine gene polymorphisms in sarcoidosis.

BACKGROUND: Sarcoidosis is a disease characterized by granuloma formation in many organs, but mostly in lung and lymph nodes. The immunopathogenic background of the disease is probably based on disregulation of immune response to different antigens. The imbalance of immune reactivity might be influenced by genetic background. In our study, we have investigated cytokine genetic polymorphisms in sarcoidosis group and compared the results with that of a group of healthy volunteers. METHODS: Thirty one sarcoidosis patients were enrolled to our study. Basic demographic data were collected. Polymorphisms in the promoter regions of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-alpha, IFN-gamma and in the translated regions of the TGF-beta, IL-1 beta, IL-2, IL-4 and IL-4RA genes were characterized. RESULTS: For IL-10, the (-819) and (-592) CC homozygosity was statistically more frequent in the sarcoidosis group compared to healthy controls. According to the haplotypes, the majority of sarcoidosis patients had IL-10 (-1082)(-819)(-592) ACC haplotype 2 compared to controls with ATA in most of the cases. CONCLUSIONS: The results of our study support the hypothesis of a genetically encoded immune regulation imbalance in sarcoidosis. The high-producer IL-10 (-819) and (-592) CC genotypes and intermediate- producer IL-10 (-1082) (-819) (-592) ACC haplotype 2 present in the majority of our sarcoidosis patients could support the role of genetically encoded disregulation of cell- mediated immune response to an unknown antigen.

Hepatocyte growth factor and antibodies to HLA and MICA antigens in heart transplant recipients.

Recent unconfirmed literature data suggest that elevated concentrations of the multifunctional cytokine hepatocyte growth factor (HGF) might be a marker of increased incidence of acute rejection after organ transplantation. The aim of this study was to test the hypothesis that HGF levels may correlate with the rejection and/or with the production of HLA and MHC Class I chain-related antigens A (MICA) specific antibodies. Sixty-three heart transplant recipients were included into the study. Hundred and eighty-five endomyocardial biopsies (EMB) obtained up to 6 months after transplantation were retrospectively analyzed for signs of cellular (CR) and antibody-mediated rejection (AMR). Pre- and post-transplant sera were tested for HGF concentrations and antibodies to HLA class I, class II and MICA antigens by xMap technology (Luminex). Pre-transplant HGF did not correlate with the incidence of CR or AMR. However, higher HGF concentrations correlated significantly with HLA antibody production before and after transplantation (P = 0.006 and P < 0.0001 respectively). Patients with both HLA class I and class II antibodies before transplantation had significantly lower AMR-free survival. Furthermore, recipients with pre-transplant donor-specific antibodies (DSA) had significantly lower AMR-free survival (50%) than recipients without pre-transplant HLA antibodies (90%) and patients with antibodies not specific to donor antigens (92%) (P = 0.005). Post-transplant MICA antibodies tended to be more frequent in patients with AMR (P = 0.063). In conclusion, elevated HGF concentrations in our study were not associated with the incidence of CR and/or AMR but with the presence of HLA-specific antibodies. Testing for DSA before heart transplantation by Luminex may be helpful for the identification of patients with increased risk of AMR.

Report from the killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop: worldwide variation in the KIR loci and further evidence for the co-evolution of KIR and HLA.

The killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop (IHIWS) sought to explore worldwide population variation in the KIR loci, and to examine the relationship between KIR genes and their human leukocyte antigen (HLA) ligands. Fifteen laboratories submitted KIR genotype and HLA ligand data in 27 populations from six broad ethnic groups. Data were analyzed for correlations between the frequencies of KIR and their known HLA ligands. In addition, allelic typing was performed for KIR2DL2 and 3DL1 in a subset of populations. Strong and significant correlations were observed between KIR2DL2, 2DL3 genotype frequencies and the frequency of their ligand, HLA-C1. In contrast, only weak associations were seen for 3DL1, 3DS1 and the HLA-Bw4 ligand. Although some aspects of the correlations observed here differ from those reported in other populations, these data provide additional evidence of linked evolutionary histories for some KIR and HLA loci. Investigation of allele-level variation for the B haplotype locus KIR 2DL2 showed that two alleles, *001 and *003, predominate in all populations in this study. Much more allelic variation was observed for the A haplotype locus 3DL1, with several alleles observed at moderate frequencies and extensive variation observed between populations.

Bronchoalveolar lavage fluid cellular characteristics, functional parameters and cytokine and chemokine levels in interstitial lung diseases.

Idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP) and sarcoidosis belong to interstitial lung diseases (ILD) where an imbalance of regulatory, profibrotic and antifibrotic cytokines is hypothesized. The relationship of bronchoalveolar lavage (BAL) fluid (BALF) cytokines, BALF cell profile and ILD course is supposed. The aim of our study was to correlate BALF cytokine and chemokine levels with BALF cellular characteristics and lung function parameters in different ILD. Twenty-two sarcoidosis, seven IPF and 11 HP patients underwent lung function tests and BAL. The BALF differential cell counts and superficial cell markers were characterized, and MCP-1, MIP-1alpha, MIP-1beta, RANTES, epithelial neutrophil-activating protein (ENA)-78, FGF, G-CSF, GM-CSF, IFN-gamma, interleukin (IL)-1alpha, IL-1RA, IL-1beta, -2beta, -4beta, -5beta, -6beta, -8beta, -10beta, -17beta, tumour necrosis factor (TNF)-alpha, thromobopoietin (Tpo) and vascular endothelial growth factor (VEGF) values measured. The BALF VEGF values were highest in sarcoidosis (P = 0.0526). IL-1RA values were higher in IPF and HP compared with sarcoidosis (P = 0.0334). IL-8/ENA-78 ratio positively correlated with BALF neutrophil counts in IPF (r = 0.89, P = 0.04). Vital capacity and TL(CO) values positively correlated with VEGF and negatively with IL-8 BALF levels in all ILDs but the correlations were most significant in sarcoidosis group. We suppose that VEGF plays a role in ILDs' early phases and has rather angiogenic than profibrotic effect. On the contrary, IL-8 is probably upregulated in advanced ILDs with prominent fibrosis and marked lung functions decline. We state that BALF VEGF, IL-8 and ENA-78 levels and IL-8/ENA-78 ratio could become useful markers of ILDs' phase, activity and prognosis. They might also be helpful in treatment modality choice.

Distribution of KIR genes in the Czech population.

Killer cells immunoglobulin-like receptors (KIRs) are a family of inhibitory and activating receptors expressed mainly by natural killer (NK) cells and few subsets of T lymphocytes. KIRs regulate NK cells' activity through interactions with specific HLA class I molecules and other yet unknown ligands presented on target cells. At present, 17 KIR genes and pseudogenes have been identified. As the number of KIR genes in different haplotypes varies, a wide range of genotypes in different ethnic populations may be observed. In our study, 125 healthy non-related Czech individuals were KIR typed both by sequence-specific primers and by sequence-specific oligonucleotide KIR genotyping methods. Thirty-eight different genotypes were observed in the Czech population and all 16 KIR genes known to date were found. Framework genes KIR 3DL3, KIR 2DL4, KIR 3DL2 and the pseudogene KIR 3DP1 were present in all individuals. The most frequent non-framework KIR genes detected in the Czech population were: KIR 2DL1 (95%), KIR 3DL1 (94%), KIR 2DS4 (92%) and the pseudogene 2DP1 (94%). Human leucocyte antigen (HLA)-C typing demonstrated prevalence of the C1/C2 heterozygosity (43%) and C1 homozygosity (41%) over the C2 heterozygosity. One hundred and twenty individuals from our panel carried at least one inhibitory KIR for the corresponding HLA-C group found in the genotype. Gene frequencies and found genotypes demonstrated similarity of the Czech population's KIR repertoire with the KIR repertoires of other Caucasian populations studied before.

Polymorphism of interleukin-18 promoter influences the onset of kidney graft function after transplantation.

It has been well recognized that the promoter polymorphisms of interleukin-18 (IL-18) influence the level of cytokine expression. In our previously published data, we showed constitutive IL-18 expression in the epithelium of renal distal tubules in patients after kidney transplantation and significantly elevated IL-18 expression during acute rejection. In this study, we evaluated the clinical significance of two functional promoter polymorphisms of the IL-18 gene at positions -607 A/C (rs1946518) and -137 C/G (rs187238) in patients after kidney transplantation and looked for associations with the onset of graft function and the incidence of rejection episodes. Promoter polymorphisms in 124 patients and 103 unrelated controls were evaluated by sequence-specific primer polymerase chain reaction and the allele, genotype and haplotype frequencies were statistically correlated. We found a statistically different distribution of the allele frequency of -607 A/C polymorphism between patients with immediate or delayed onset of kidney graft function. Data showed that the C allele, which contributes to higher IL-18 expression, is more frequent in patients with delayed onset of function (P = 0.03, odds ratio = 1.93; 95% confidence interval = 1.15-3.25). A/C single nucleotide polymorphisms of the IL-18 promoter at position -607 may influence the onset of early kidney allograft function.

[Acute humoral rejection of renal transplant]. / Akutní humorální rejekce transplantované ledviny.

Acute humoral rejection (AHR) is a rare complication which often results in the loss of kidney graft. The objective of this retrospective monocentric study was to evaluate two different approaches to AHR. Documentation of 730 patients was analysed, who underwent renal transplantation between 2002 and 2005. From 2002 to 2003, patients with AHR were treated with 5 plasmaphereses (PF group, n = 13), and from 2004 to 2005 with a combination of 5 PF and intravenous immunoglobulins (PF + IVIG, 0.5 g/kg, n = 8). Data for the period of one year post-transplant was analysed. AHR occurred in 21 out of 730 patients (2.9%). Survival of grafts in the 6th month and in the 1st year was significantly higher for the PF + IVIG group than for the PF group only (p < 0.05). Patient survival was similar in both groups. The incidence of infectious complications was similar in both groups. There was a higher incidence of acute cellular rejections in the PF group (46.2 vs. 14.3%) in control rebiopsies (performed due to deteriorated graft function or in order to check the efficiency of the treatment). It can be concluded that acute humoral rejection of transplanted kidney is a rare complication which can be treated by the combination of plasmaphereses and intravenous immunoglobulins.

Cytokine gene polymorphisms in the Dutch population.

Numerous studies have shown that variations in the production and activity of cytokines influence the susceptibility and/or resistance to various infectious agents, autoimmune diseases, and cancer, as well as the predisposition to allograft rejection. Differences in the production of cytokines between individuals are often caused by single nucleotide polymorphisms (SNP) in the promoter or coding regions of cytokine genes. The cytokine polymorphisms of 107 unrelated Caucasian individuals originating from various parts of the Netherlands were studied and compared with the results of two European (Czech and Italian) populations. Twenty-two SNPs of 13 different cytokine genes were analysed. To test the Hardy-Weinberg equilibrium, allele frequencies were estimated by direct gene counting. Evaluation of the allele frequencies of the Dutch, Italian and Czech populations showed that five SNPs were significantly different between the Dutch and the Italians, while these SNPs did not vary between the Dutch and the Czechs. This analysis, in combination with other types of immune profiling, may be helpful for prediction of the clinical outcome of various infectious and immune-related disorders, as well as for estimation of the risk for rejection and graft vs. host disease after organ or stem cell transplantation.

Correlation of IL-1alpha and IL-4 gene polymorphisms and clinical parameters in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a serious disease characterized with progressive scarring of the lungs in which a genetic background is supposed. We have tested correlation of promotor regions of IL-1alpha and IL-4 gene polymorphisms with clinical parameters in IPF. We investigated the group of 30 patients with IPF. The correlations of vital capacity (VC) and diffusing capacity for carbon monoxide (DL(CO)), bronchoalveolar lavage (BAL) fluid cell counts and high resolution computed tomography (HRCT) alveolar and interstitial scores with different genotypes of IL-4 at (-1098), (-590) and (-33) positions and IL-1 alpha at (-889) position were tested. The PCR method was used for genotyping. The carriers of CT genotype at IL-1 alpha (-889) position had higher VC at the time of diagnosis. The CC genotype at this position was more frequent in patients with higher counts of HLADR+ T lymphocytes in BAL. The GT genotype at IL-4 (-1098) position correlated with higher counts of CD4(+) T lymphocytes, and inversely the TT genotype with higher counts of CD8(+) T lymphocytes in BAL fluid. According to dynamic changes of HRCT score the CT genotype at IL-4 (-33) was more frequent in patients with progressive disease compared to that with stable disease. We assume from our data that the gene polymorphisms of the promotor region of IL-4 at position (-1098) and (-33) and IL-1 alpha at position (-889) are likely to play a pathogenic role in IPF and in modification of its clinical presentation and severity.

Th1/Th2 cytokine gene polymorphisms in patients with idiopathic pulmonary fibrosis.

We investigated 30 patients with idiopathic pulmonary fibrosis (IPF) and 103 healthy volunteers for the cytokines polymorphisms of the IL-1alpha, IL-1beta, IL-1R, IL-1RA, IL-2, IL-4, IL-6, IL-10, IL-12, tumor necrosis factor-alpha, interferon-gamma, transforming growth factor-beta, IL-1beta, IL-2, IL-4, and IL-4RA genes. The strongest correlation of a genotype with the disease was found for gene polymorphisms at the promotor region of IL-4, where the CT genotypes at the positions (-590) and (-33) were more frequent in the IPF group (P < 0.0001, P(corr) < 0.0022; vs P < 0.0001, P(corr) < 0.0022). Our results support the idea of the pathogenic role of cytokine gene polymorphisms in the etiology and pathogenesis of IPF, with emphasize on the IL-4 promotor gene polymorphisms.

[Characterization of null alleles in human histocompatibility complex antigens (HLA)]. / Charakterizace nulových alel v komplexu lidských histokompatibilních antigenu (HLA).

The widespread application of DNA techniques in medicine and biology has allowed the typing of human leukocyte antigens (HLA) at the molecular level. Comparative studies between serological and molecular biology methods have shown the existence of null alleles, which code HLA antigens with low or no cell surface expression. Null alleles are not detectable by standard serological typing methods and may be overlooked/or incorrectly assigned by available DNA methods. Although null alleles are infrequent in human populations, they should not be ignored. Errors in typing of null alleles may cause complications in the evaluation of HLA matching of donor/recipient pairs that were originally considered HLA-compatible. The detection of null alleles and their frequency in various populations requires typing of a large number of individuals by both serological and DNA-based methods. Knowledge of the haplotype(s) associated with null alleles may be helpful for their identification. For this purpose, it is necessary to perform family studies.

Fluorescence-based automated fragment analysis of microsatellite polymorphism within the transmembrane region of the MIC-A gene.

MHC class I chain-related genes (MIC) are located within the MHC class I region of chromosome 6. Sequence analysis of the MIC-A gene showed a trinucleotide repeat (GCT) microsatellite polymorphism within the transmembrane region. So far, six alleles of the exon 5 of the MIC-A gene, which consist of 4, 5, 6, 9 and 10 repetitions of GCT, or five repetitions of GCT with an additional nucleotide insertion (GGCT), have been identified. Recent works support the findings that MIC-A is associated with several autoimmune diseases. In our work we present a modification of a method used for microsatellite polymorphism detection within the transmembrane region of the MIC-A gene. It is the ALFexpress fluorescence-based automated fragment analysis. We also present the frequencies of MIC-A exon 5 alleles found in the Czech population. We have identified five alleles of the transmembrane region of MIC-A, which comprise 4, 5, 6 and 9 repetitions or five repetitions with an additional nucleotide insertion. The most frequent allele was A5.1 (59.3%) and the less frequent was the allele A5 (20.0%). No A7, A8 or A10 alleles were identified.

Donor-specific antibodies and kidney transplant rejection.

The role played by non-complement binding antibodies after kidney transplantation is still not satisfactorily elucidated. A growing number of publications suggest that the detection of antibodies to donor HLA antigens by more sensitive methods than the standard complement-dependent cytotoxicity test is often associated with acute and chronic immunological complications and generally worse graft prognosis. In this review, we briefly discuss several recent reports on the clinical significance of non-cytotoxic anti-HLA antibodies, which might have important implications for patient immunosuppression and management after organ transplantation.