BACKGROUND: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells. METHODS: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation. RESULTS: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age. CONCLUSIONS: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD.

• MeSH
• biologické markery analýza   MeSH
• Crohnova nemoc * diagnóza   MeSH
• dítě MeSH
• idiopatické střevní záněty * komplikace   MeSH
• inhibitory TNF MeSH
• lidé MeSH
• střevní sliznice patologie   MeSH
• T-lymfocyty - podskupiny MeSH
• ulcerózní kolitida * diagnóza   MeSH
• zánět patologie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

In this review, we discuss a possible central role of T-cell help in severe forms of graft damage mediated by donor-specific HLA antibodies (DSA). Some kidney transplant recipients with pretransplant DSA show a high graft failure rate, whereas in other patients DSA do not harm the transplanted kidney and in most cases, disappear shortly after transplantation. Analyzing 80 desensitized highly immunized kidney transplant recipients and another multicenter cohort of 385 patients with pretransplant HLA antibodies, we reported recently that an ongoing T-cell help from an activated immune system, as measured by an increased level of soluble CD30 in serum, might be necessary for the DSA to exert a deleterious effect. Patients positive for both pretransplant DSA and sCD30 appear to require special measures, such as the elimination of DSA from the circulation, potent immunosuppression, good HLA-matching, and intense post-transplant monitoring, whereas exclusion of DSA-positive patients from transplantation in the absence of high sCD30 may not be justified in all cases, even if the pretransplant DSA are strong and complement-activating.

• MeSH
• antigen Ki-1 imunologie   MeSH
• dárci tkání MeSH
• HLA antigeny imunologie   MeSH
• imunosupresiva MeSH
• isoprotilátky krev   MeSH
• kohortové studie MeSH
• komplement MeSH
• lidé MeSH
• myši MeSH
• přežívání štěpu imunologie   MeSH
• protilátky imunologie   MeSH
• rejekce štěpu imunologie   MeSH
• renální insuficience krev   imunologie   MeSH
• T-lymfocyty imunologie   MeSH
• transplantace ledvin MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: It is an unresolved issue why some kidney transplant recipients with pretransplant donor-specific HLA antibodies (DSA) show a high transplant failure rate, whereas in other patients DSA do not harm the graft. We investigated whether help from preactivated T-cells might be necessary for DSA to exert a deleterious effect. METHODS: The impact of pretransplant DSA and immune activation marker soluble CD30 (sCD30) on 3-year graft survival was analyzed in 385 presensitized kidney transplant recipients. FINDINGS: A deleterious influence of pretransplant DSA on graft survival was evident only in patients who were positive for the immune activation marker sCD30. In the absence of sCD30 positivity, 3-year graft survival was virtually identical in patients with or without DSA (83.1±3.9% and 84.3±2.8%, P=0.81). A strikingly lower 3-year graft survival rate of 62.1±6.4% was observed in patients who were both sCD30 and DSA positive (HR 2.92, P<0.001). Even in the presence of strong DSA with ≥5000 MFI, the 3-year graft survival rate was high if the recipients were sCD30 negative. INTERPRETATION: Pretransplant DSA have a significantly deleterious impact on graft survival only in the presence of high pretransplant levels of the activation marker sCD30.

• MeSH
• antigen Ki-1 krev   MeSH
• chronické selhání ledvin terapie   MeSH
• dárci tkání MeSH
• dospělí MeSH
• ELISA MeSH
• HLA antigeny krev   imunologie   MeSH
• imunitní systém metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• přežívání štěpu MeSH
• proporcionální rizikové modely MeSH
• retrospektivní studie MeSH
• senioři MeSH
• T-lymfocyty cytologie   metabolismus   MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Our retrospective study was aimed to assess the relevance of pre- and post-transplant measurements of serum concentrations of the soluble CD30 molecule (soluble CD30, sCD30) and the cytokine Hepatocyte growth factor (HGF) for prediction of the risk for development of antibody-mediated rejection (AMR) in kidney transplant patients. Evaluation of sCD30, HGF levels and the presence of HLA-specific antibodies in a cohort of 205 patients was performed before, 2weeks and 6months after transplantation. Patients were followed up for kidney graft function and survival for two years. We found a tendency of higher incidence of AMR in retransplanted patients with elevated pre-transplant sCD30 (≥100U/ml) (p=0.051), however no such correlation was observed in first-transplant patients. Kidney recipients with simultaneously high sCD30 and HLA-specific antibodies (sCD30+/Ab+) before transplantation had significantly lower AMR-free survival compared to the other patient groups (p<0.001). HGF concentrations were not associated with the incidence of AMR at any time point of measurement, nevertheless, the combined analysis HGF and sCD30 showed increased incidence of AMR in recipients with elevated pretransplant sCD30 and low HGF levels. Conclusion: the predictive value of pretransplant sCD30 for the development of antibody-mediated rejection after transplantation is significantly potentiated by the co-presence of HLA specific antibodies. The role of HGF as a rejection-protective factor in patients with high pretransplant HGF levels would need further investigation.

• MeSH
• antigen Ki-1 krev   imunologie   MeSH
• biologické markery krev   MeSH
• časové faktory MeSH
• hepatocytární růstový faktor krev   imunologie   MeSH
• HLA antigeny imunologie   MeSH
• homologní transplantace MeSH
• isoprotilátky krev   imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• rejekce štěpu krev   mortalita   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• transplantace ledvin imunologie   mortalita   MeSH
• tvorba protilátek imunologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• práce podpořená grantem MeSH

Hypokomplementemie C1q, C3, C4 složky, celková hemolytická aktivita komplementu, protilátky anti C1q u nemocných se SLE s přítomností a bez přítomnosti lupusové glomerulonefritidy, klinické a laboratorní korelace, vztah k histologickému typu nefritidy Vztah apoptotických indexů T a B lymfocytů periferní krve stanovených průtokovou cytometrií metodou dvojitého barvení a parametrů celkové apoptotické zátěže organismu (sCD30 a sCD40L) k aktivaci komplementového systému u nemocných s lupusovou nefritidou Hladiny molekuly BLyS/Baff a její renální exprese u nemocných se SLE s přítomností a bez přítomnosti lupusové nefritidy, vztahy k histologickému typu nefritidy Vztahy uvedených parametrů k protilátkové a klinické aktivitě systémového lupus erytematodes (anti dsDNA protilátky, anti DNP protilátky, systémy ECLÄM, SLEDAI, SLICC).; Hypocomplementemia C1q, C3, C4, total hemolytic activity of complement, antibodies anti C1q in patietns with SLE with and without lupus nephrtis, clinical and laboratory correlations, relation to histological type nephritis Relation of apoptotic indicesof T and B cells from peripheral blodd measured by flow-cytometry and double staining, parameters of apoptotic load of organism (sCD30 a sCD40L) to activation of complement system in patients with lupus nephritis Serum levels and renal exression of BLyS/Baff in patients with SLE with and without lupus nephritis, relation to histological type of neprhitis Relation of measured parameters to antibody and clinical activity of SLE (dsDNA antibodies, anti DNP antibodies, system ECLAM, SLEDAI, SLICC).

• MeSH
• apoptóza MeSH
• biopsie MeSH
• ELISA MeSH
• komplement C1q antagonisté a inhibitory   imunologie   MeSH
• komplement MeSH
• ledviny MeSH
• lymfocyty MeSH
• nefritida při lupus erythematodes MeSH
• serinové proteasy asociované s proteinem vázajícím mannosu MeSH
• systémový lupus erythematodes MeSH

• Konspekt
• Biochemie. Molekulární biologie. Biofyzika
• NLK Obory
• nefrologie
• biochemie
• NLK Publikační typ
• závěrečné zprávy o řešení grantu IGA MZ ČR

CD30/CD30L and CD40/CD40L are molecules from the tumor necrosis factor (TNF) superfamily. They have a major effect on communications between the B and T cells, which leads to control of maturation, proliferation, and apoptosis of those cells. The aim of this study was to compare the levels of a soluble form of CD30 (sCD30) and a soluble ligand CD40 (sCD40L) in patients with systemic lupus erythematosus (SLE) (n=65) and healthy controls (sCD30 n=20, sCD40L n=10) with other parameters of SLE activity. Patients were divided into subgroups according to presence or absence of lupus nephritis (LN; 33 with LN, 32 without LN). The serum levels of selected parameters were assessed also in the subgroups with low active disease characterized by European Lupus Activity Measure (ECLAM) at most 3(n=29) and active disease with ECLAM more than 3 (n=36). The serum levels of sCD30 were 66.0+/-40.2 UI/ml in the whole group. The mean serum levels were 60.0+/-45.2 UI/ml in the subgroups with LN, 67.1+/-38.9 UI/ml in the subgroup without LN, 80.2+/-51.9 UI/ml in the subgroup with active disease, 55.4+/-24.1 UI/ml in the subgroup with low active disease, and finally, 40.1+/-19.2 U/ml in the controls. Significant differences were found between the SLE patients and controls (p=0.0001) and between the active and nonactive groups (p=0.002). A correlation was found between levels of CD30 and ECLAM (r=0.25, p

• MeSH
• antigen Ki-1 krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• financování organizované MeSH
• lidé středního věku MeSH
• lidé MeSH
• ligand CD40 krev   MeSH
• mladiství MeSH
• senioři MeSH
• systémový lupus erythematodes diagnóza   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• Publikační typ
• abstrakt z konference MeSH

The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration. The median concentrations of the sCD30 molecule were identical in C4d-positive and C4d-negative patients before and after transplantation (65.5 vs. 65.0 and 28.2 vs. 36.0 U/ml, respectively). C4d+ patients who developed DSA de novo had a tendency to have higher sCD30 levels before transplantation (80.7+/-53.6 U/ml, n=8) compared with C4d-negative patients (65.0+/-33.4 U/ml, n=15). Soluble CD30 levels were evaluated as positive and negative (>or=100 U/ml and <100 U/ml respectively) and the sensitivity, specificity and accuracy of sCD30 estimation with regard to finding C4d deposits in peritubular capillaries were determined. The sensitivity of sCD30+ testing was generally below 40%, while the specificity of the test, i.e. the likelihood that if sCD30 testing is negative, C4d deposits would be absent, was 82%. C4d+ patients who developed DSA de novo were evaluated separately; the specificity of sCD30 testing for the incidence of HR in this cohort was 86%. CONCLUSION: We could not confirm in our study that high sCD30 levels (>or=100 U/ml) might be predictive for the incidence of HR. Negative sCD30 values might be however helpful for identifying patients with a low risk for development of DSA and antibody-mediated rejection.

• MeSH
• antigen Ki-1 analýza   MeSH
• dospělí MeSH
• financování organizované MeSH
• homologní transplantace MeSH
• komplement C4b analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• peptidové fragmenty analýza   MeSH
• protilátky imunologie   MeSH
• rejekce štěpu imunologie   MeSH
• senioři MeSH
• transplantace ledvin imunologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

• Publikační typ
• abstrakty MeSH