RESUMEN
Proinflammatory cytokines and their inhibitors are involved in the regulation of multiple immune reactions including response to transplanted organs. In this prospective study, we evaluated changes in serum concentrations of six IL-1 family cytokines (IL-1 alpha, IL-1 beta, IL-1RA, IL-18, IL-18BP, and IL-36 beta) in 138 kidney allograft recipients and 48 healthy donors. Samples were collected before transplantation and then after one week, three months and one year, additional sera were obtained at the day of biopsy positive for acute rejection. We have shown, that concentrations of proinflammatory members of the IL-1 family (IL-1ß, IL-18, IL-36 ß) and anti-inflammatory IL-18BP decreased immediately after the transplantation. The decline of serum IL-1RA and IL-1α was not observed in subjects with acute rejection. IL-18, including specifically its free form, is the only cytokine which increase serum concentrations in the period between one week and three months in both groups of patients without upregulation of its inhibitor, IL-18BP. Serum concentrations of calculated free IL-18 were upregulated in the acute rejection group at the time of acute rejection. We conclude that IL-1 family cytokines are involved mainly in early phases of the response to kidney allograft. Serum concentrations of free IL-18 and IL-18BP represent possible biomarkers of acute rejection, and targeting IL-18 might be of therapeutic value.
Asunto(s)
Aloinjertos , Biomarcadores , Rechazo de Injerto , Interleucina-18 , Trasplante de Riñón , Humanos , Interleucina-18/sangre , Masculino , Femenino , Biomarcadores/sangre , Rechazo de Injerto/inmunología , Rechazo de Injerto/sangre , Persona de Mediana Edad , Adulto , Péptidos y Proteínas de Señalización Intercelular/sangre , Interleucina-1/sangre , Estudios Prospectivos , Trasplante Homólogo/métodosRESUMEN
IL-1-related cytokines share similarities in their receptor distribution and signalling pathways; however, overlapping actions of these cytokines have not been clearly demonstrated. The aim of our study was to compare the capacity of different IL-1-related cytokines to stimulate production and release of multiple CC and CXC chemokines by epithelial cells. The chemokine gene expression was studied using a cDNA array system in human alveolar type-II like cells A549 stimulated by IL-1ß, IL-18, and IL-33. The chemokine levels in culture supernatants were measured using multiplex immunoluminometric assay or by ELISA. In repetitive experiments, in response to IL-1ß epithelial cells expressed mRNA for CCL2, CCL5, CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL8, and CXCL11. In contrast, induction of epithelial cells by IL-33 and IL-18 resulted only in moderate up-regulation of a few CC or CXC chemokines compared to the potent effect of IL-1ß stimulation. We conclude from our data that individual members of the IL-1 family, although related in molecular structure and signalling pathways, widely differ in their capacity to stimulate epithelial production of both CXC and CC chemokines.
Asunto(s)
Quimiocinas/genética , Células Epiteliales/metabolismo , Interleucina-1/farmacología , Pulmón/patología , Línea Celular Tumoral , Quimiocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , HumanosRESUMEN
BACKGROUND AND OBJECTIVE: The course of atopic dermatitis (AD) in childhood is characterized by typical changes in phenotype, including a shift from skin involvement to respiratory allergy usually around the third year of age. We thus designed a prospective study to monitor the outcome of severe AD and to investigate the association between cytokine gene polymorphisms and clinical manifestations. METHODS: Clinical and laboratory follow-up of 94 patients with severe AD and 103 healthy controls was performed using routine methodology. Allele, genotype, and haplotype frequencies of single nucleotide polymorphisms of 13 selected cytokine/receptor genes were analyzed using PCR with sequence-specific primers. RESULTS: In our study, genotypes of 7 polymorphisms--LL-4 -1098G/T and -590C/T, IL-6 -174C/G and nt565A/G, and IL-10 -1082A/G, -819C/T, and -592A/C were significantly associated with atopic AD (P < .05). A significant association was also found for TNF-alpha AA and IL-4 GC haplotypes and AD. We confirm the progressive clinical improvement of AD together with a decrease in the severity index SCORAD (SCORing atopic dermatitis) during childhood (P < .05). We found significant differences between IL-4Ralpha +1902 A/G and positivity of tree pollen-specific IgE (P < .05) in the AD group. Moreover, a weak association was also found between IL-10 -819C/T and IL-10 -590A/C and the appearance of allergic rhinitis (P < 0.1). CONCLUSIONS: We confirmed a clinical shift in allergic phenotype in the first 3 years of life, and showed an association between IL-4, IL-6, and IL-10 polymorphisms and AD. Our data indicate that IL-4alpha and IL-10 polymorphisms may be considered predictive factors of respiratory allergy in children with AD.
Asunto(s)
Dermatitis Atópica/genética , Interleucinas/genética , Factor de Necrosis Tumoral alfa/genética , Alelos , Estudios de Casos y Controles , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Haplotipos/genética , Humanos , Lactante , Recién Nacido , Masculino , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Rinitis Alérgica Estacional/genéticaRESUMEN
In the era of COVID-19 pandemic, organ transplantation programs were facing serious challenges. The lung transplantation donor pool was extremely limited and SARS-CoV-2 viral load assessment has become a crucial part of selecting an optimal organ donor. Since COVID-19 is a respiratory disease, the viral load is thought to be more important in lung transplantations as compared to other solid organ transplantations. We present two challenging cases of potential lung donors with a questionable COVID-19 status. Based on these cases, we suggest that the cycle threshold (Ct) value should always be requested from the laboratory and the decision whether to proceed with transplantation should be made upon complex evaluation of diverse criteria, including the nasopharyngeal swab and bronchoalveolar lavage PCR results, the Ct value, imaging findings and the medical history. However, as the presence of viral RNA does not ensure infectivity, it is still to be clarified which Ct values are associated with the viral viability. Anti-SARS-CoV-2 IgA antibodies may support the diagnosis and moreover, novel methods, such as quantifying SARS-CoV-2 nucleocapsid antigen in serum may provide important answers in organ transplantations and donor selections.
Asunto(s)
COVID-19/diagnóstico , Selección de Donante , Trasplante de Pulmón , Pulmón/virología , SARS-CoV-2/aislamiento & purificación , Donantes de Tejidos , Adulto , Líquido del Lavado Bronquioalveolar/virología , COVID-19/virología , Prueba de COVID-19 , Femenino , Humanos , Pulmón/cirugía , Trasplante de Pulmón/efectos adversos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Medición de Riesgo , Factores de Riesgo , Carga ViralRESUMEN
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.
Asunto(s)
Rechazo de Injerto/patología , Trasplante de Riñón/efectos adversos , Monocitos/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Rechazo de Injerto/etiología , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Estudios Prospectivos , Adulto JovenRESUMEN
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.
Asunto(s)
Rechazo de Injerto/etiología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/inmunología , Factor de Crecimiento de Hepatocito/sangre , Antígenos de Histocompatibilidad Clase I/inmunología , Isoanticuerpos/sangre , Enfermedad Aguda , Adulto , Biomarcadores/sangre , Femenino , Rechazo de Injerto/diagnóstico , Trasplante de Corazón/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
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.
Asunto(s)
Citocinas/genética , Polimorfismo Genético , Sarcoidosis/genética , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , República Checa , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Homocigoto , Humanos , Interleucina-10/genética , Masculino , Persona de Mediana Edad , Fenotipo , Regiones Promotoras Genéticas , Sarcoidosis/etnología , Sarcoidosis/inmunología , Índice de Severidad de la Enfermedad , Población Blanca/genéticaRESUMEN
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.
Asunto(s)
Citocinas/genética , Leiomioma/genética , Polimorfismo Genético , Células TH1/fisiología , Células Th2/fisiología , Adulto , Femenino , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Leiomioma/patología , Persona de Mediana Edad , Regiones Promotoras Genéticas , Adulto JovenRESUMEN
M2 macrophages expressing CD163 are known to suppress immune responses but have been also found in biopsies of patients with chronic kidney allograft injury associated with interstitial fibrosis. The aim of our study was to evaluate the expression of CD163 in blood monocytes, precursors of tissue macrophages, in kidney allograft recipients with uncomplicated outcome (n=94) compared with those developing acute rejection (n=44). Blood samples were collected before the transplantation and at 1 week, 1 month and 1 year. The expression of CD163 increased during the first week after the transplantation not only in classical (CD14+CD16-) but also in intermediate (CD14+CD16+) and nonclassical (CD14lowCD16+) monocytes in all patients regardless of their rejection status. In patients developing acute rejection, higher pre-transplant expression of CD163 on blood monocytes was found. In vitro experiments confirmed strong induction of membrane CD163 on monocytes together with CD206 (an alternative marker of M2 macrophages) in response to IL-10. We assume from our data that dramatic upregulation of CD163 by peripheral blood monocytes may have a pathophysiological role in early phases after kidney allograft transplantation and high pre-transplant expression of CD163 on blood monocytes might be involved in events leading to acute rejection.
Asunto(s)
Antígenos CD/sangre , Antígenos de Diferenciación Mielomonocítica/sangre , Trasplante de Riñón , Macrófagos/metabolismo , Monocitos/metabolismo , Receptores de Superficie Celular/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Aloinjertos , Biomarcadores/sangre , Femenino , Rechazo de Injerto/sangre , Rechazo de Injerto/etiología , Humanos , Interleucina-10/metabolismo , Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Regulación hacia Arriba , Adulto JovenRESUMEN
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.
Asunto(s)
Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Enfermedades Pulmonares Intersticiales/inmunología , Enfermedades Pulmonares Intersticiales/patología , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función RespiratoriaRESUMEN
Permanent irritation of the peritoneum during peritoneal dialysis (PD) treatment leads to local chronic inflammation and subsequently activation of processes driving fibrogenesis in the long-term. The aim of the study was to compare the peritoneal effluent transcriptome of 20 patients treated less and 13 patients treated more than 2 years using microarray analysis. An increased expression of genes associated with an immune response was observed in long-term treated patients with well preserved peritoneal function, when compared to patients treated less than 2 years. From 100 genes highly expressed in long-term patients, a significant up-regulation of six was found by RT-qPCR: LY9 (lymphocyte antigen 9), TNSFR4 (tumor necrosis factor receptor superfamily, member 4), CD 79A (CD79a molecule), CCR7 (chemokine C-C receptor 7), CEACAM1 (carcinoembryonic antigen-related cell adhesion molecule 1) and IL2RA (interleukin 2 receptor alpha chain). Furthermore, the effluent cell population was analysed. A positive relationship between the number of granulocytes and NK cells on one hand, and duration of PD treatment on the other, was shown. We conclude, that the mechanisms of adaptive immunity promoting T helper 2 cells response are activated in the long-term before functional alterations develop. It consequently might trigger the fibrosis promoting processes.
Asunto(s)
Inmunidad Adaptativa/genética , Enfermedades Renales/terapia , Diálisis Peritoneal/efectos adversos , Peritoneo/inmunología , Líquido Ascítico/inmunología , Líquido Ascítico/metabolismo , Femenino , Fibrosis , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Masculino , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritoneo/metabolismo , Peritoneo/patología , Factores de Tiempo , Transcriptoma , Resultado del TratamientoRESUMEN
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.
Asunto(s)
Frecuencia de los Genes , Receptores KIR/genética , República Checa , Humanos , Seudogenes , Población Blanca/genéticaRESUMEN
Under Global Initiative for Asthma guidelines, the clinical control of disease activity and the adjustment of treatment in patients with asthma are based on symptoms, use of rescue medication, lung function and peak expiratory flow measurement (standard strategy). We investigated whether a strategy to reduce the number of sputum eosinophils (EOS strategy) gives better clinical control and a lower exacerbation rate compared with the standard strategy. Fifty-five patients with moderate to severe asthma entered this open, randomized, parallel-group study and visited the out-patient department every 3 months for 18 months. The dose of corticosteroids was adjusted according to the standard strategy or the percentage of sputum eosinophils (EOS strategy). During the study period, the EOS strategy led to a significantly lower incidence of asthma exacerbations compared with the standard strategy group (0.22 and 0.78 exacerbations per year per patient, respectively). There were significant differences between the strategies in time to first exacerbation.
Asunto(s)
Corticoesteroides/uso terapéutico , Asma/tratamiento farmacológico , Eosinófilos/efectos de los fármacos , Esputo/citología , Corticoesteroides/administración & dosificación , Adulto , Asma/complicaciones , Asma/patología , Eosinofilia/complicaciones , Eosinofilia/tratamiento farmacológico , Eosinofilia/patología , Eosinófilos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
As an autoimmune disease, type 1 diabetes mellitus (DM) can be associated with other autoimmune disorders. The aim of this study was to detect subclinically associated autoimmune thyroid disease, coeliac disease, and Addison's disease. The presence of autoantibodies was evaluated with special regard to the control of diabetes and to the clinical status of the patient. Fifty-one type 1 diabetic patients (22 men, 29 women, mean age 37+/-11 years, mean duration of diabetes 16+/-13 years) were included into this study. Specific antibodies to islet antigens--glutamic acid decarboxylase (GAD65), protein thyrosine phosphatase IA-2alpha, and to thyroid autoantigens--thyroid microsomal peroxidase (TPO) and thyroglobulin (TG) and also thyroid stimulating hormone (TSH) were measured by RIA. Autoantigens of the small intestine--tissue transglutaminase autoantibodies (ATTG), IgA and IgG antibodies to gliadin (AGA-IgA, AGA-IgG) were evaluated by ELISA. Endomysial autoantibodies (EMA) and adrenal cortex antibodies (ACA) were detected by indirect immunofluorescence microscopy. Eleven new cases of thyreopathy (22 % of patients) were detected by the assessment of thyroid autoantibodies and TSH. Two new cases of thyreotoxicosis were diagnosed during the study. Coeliac disease was diagnosed in at least two cases. Addison's disease was not diagnosed, although the ACA were positive in two patients. No influence of single or combined autoantibody positivity on the control of diabetes was found if normal organ function was preserved. In both patients with thyreotoxicosis the control of diabetes was worsened and improved after treatment. The screening of autoantibodies in type 1 diabetic patients could reveal subclinical cases of AITD or coeliac disease. Subclinical forms of these disorders have no influence on diabetes control. However, impaired organ function may be associated with the worsened control of diabetes as we demonstrated on two newly diagnosed cases of thyreotoxicosis. We suggest the need for the follow-up of patients with positive autoantibodies because further deterioration of the respective organs can be expected.
Asunto(s)
Enfermedad de Addison/inmunología , Autoinmunidad , Enfermedad Celíaca/inmunología , Diabetes Mellitus Tipo 1/inmunología , Tiroiditis Autoinmune/inmunología , Enfermedad de Addison/complicaciones , Corteza Suprarrenal/inmunología , Adulto , Autoanticuerpos/sangre , Enfermedad Celíaca/complicaciones , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Gliadina/inmunología , Glutamato Descarboxilasa/inmunología , Humanos , Inmunoglobulinas Estimulantes de la Tiroides/sangre , Isoenzimas/inmunología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Tiroiditis Autoinmune/complicaciones , Transglutaminasas/inmunologíaRESUMEN
Improvements in immunosuppressive therapy during the past decade brought about improvements of the long term tolerance of organ allografts. However, the long-term immunosuppressive therapy has an important limitation, because it can increase the risk of cardivascular diseases, infections and tumors. As compared with age-matched healthy population, organ-transplant recipients have an increased incidence of tumors.
Asunto(s)
Neoplasias/etiología , Trasplante de Órganos/efectos adversos , Humanos , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Factores de Riesgo , Inmunología del TrasplanteRESUMEN
Atherosclerosis pathology is the interplay between high intravascular LDL particle concentration and monocyte/macrophage presence within the sub-endothelial space of the artery. In this project, phenotypes of macrophages connected with subclinical inflammation in adipose tissue of living kidney donors were studied. Samples of subcutaneous adipose tissue of living kidney donors (n=36) were exposed to collagenase. Stromal vascular fraction (SVF) was eluted from the samples, then labeled with monoclonal antibodies (anti-CD14 and anti-calprotectin), conjugated with fluorochromes and analyzed by flow cytometry. The positive correlation between the number of total macrophages and calprotectin-positive macrophages with BMI in the subcutaneous adipose tissue of postmenopausal women was demonstrated (p<0.05; R=0.43 and p<0.01; R=0.60), whereas no positive correlation in premenopausal women and men was shown. In conclusion, we documented a significant effect of BMI increase on the presence of total macrophages in adipose tissue of postmenopausal women, in contrast to premenopausal women. This difference was much more pronounced when proinflammatory macrophages with membrane-bound calprotectin were analyzed.
Asunto(s)
Índice de Masa Corporal , Macrófagos/metabolismo , Fenotipo , Posmenopausia/metabolismo , Grasa Subcutánea/metabolismo , Tejido Adiposo/metabolismo , Adulto , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The soluble form of the leukocyte membrane antigen CD14 is known to increase the sensitivity of endothelial and epithelial cell lines to bacterial lipopolysaccharide (LPS). This molecule also directly induces cytokine production in monocytes. Here, the effect of sCD14 and LPS on the release of IL-6 and IL-8 by human bronchial epithelial cells (HBECs) was studied. Soluble CD14 induced cytokine production both in the presence and absence of LPS. In addition, neither sCD14 nor anti-CD14 monoclonal antibody which blocks the interaction of LPS with CD14 had any effect on the binding of LPS to HBECs. These data suggest that sCD14 may induce the release of IL-6 and IL-8 from HBECs. However, the binding of LPS to bronchial epithelium appears to be mediated by CD14-independent mechanisms.
Asunto(s)
Bronquios/inmunología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Receptores de Lipopolisacáridos/metabolismo , Bronquios/citología , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Fluoresceína-5-Isotiocianato , Humanos , Receptores de Lipopolisacáridos/farmacología , Lipopolisacáridos/farmacología , Mitógenos/farmacologíaRESUMEN
Procalcitonin (PCT) represents a new marker of systemic inflammatory reactions of the body to infections. PCT is selectively induced by severe bacterial infections leading to sepsis or multiorgan dysfunction syndrome. The aim of our study was to test PCT as a postoperative infection marker in heart and kidney transplant patients compared with healthy subjects and patients with localized lung-inflammatory processes without a manifest systemic response. PCT concentrations were measured by an immunoluminometric assay (ILMA) in a total of 419 serum samples. Normal serum levels were in the range of 0.08-0.6 ng/ml. Operative trauma associated with heart (not kidney) transplantation induced a transient increase in PCT levels to 7-10 ng/ml with a decline to normal levels within 2-3 days in most patients. Severe bacterial infections dramatically augmented serum PCT concentrations reaching values of 46-297 ng/ml in the most critical periods. Good response to antibiotic therapy was associated with a decline in serum PCT concentrations. Acute rejection or cytomegalovirus infections did not significantly increase the serum PCT levels. Localized pulmonary infections showed either no, or only a limited increase, in the serum PCT levels (max. 7 ng/ml). We conclude from our data that PCT can be used as a sensitive marker to differentiate systemic bacterial infections from other complications in organ transplantation.
Asunto(s)
Infecciones Bacterianas/inmunología , Calcitonina/sangre , Rechazo de Injerto/inmunología , Trasplante de Corazón , Trasplante de Riñón , Precursores de Proteínas/sangre , Infecciones Bacterianas/sangre , Biomarcadores , Péptido Relacionado con Gen de Calcitonina , HumanosRESUMEN
The multifunctional cytokine IL-6, which can be locally produced by human bronchial epithelial cells (HBECs), has been found to play a role in IL-4 dependent IgE synthesis. Since the allergic reaction in bronchial asthma is associated with the upregulation of IL-4 and Th2 type of immune response, the purpose of our study was to assess whether IL-4 and related cytokines IL-10 and IL-13 regulate IL-6 release by HBEC s. HBECs were obtained by bronchial brushing, cultured in LHC-9/RPMI 1640. At the third passage the cells were stimulated with cytokines (0.1-20 ng/ml) diluted in unsupplemented media for 24 h. The supernatants were tested for IL-6 content by sandwich ELISA. Unstimulated HBECs produced detectable amounts of IL-6 (368+/-25 pg/ml). Exposure to IL-10 (368+/-22 pg/ml) and IL-13 (395+/-6 pg/ml) resulted in little changes. IL-4 caused a slight but significant increase in IL-6 release (530+/-45 pg/ml), P<0.05, TNFalpha (1657+/-85 pg/ml) and IFNgamma (1953+/-37 pg/ml) showed strong induction of IL-6 release in HBECs (P<0.005 and P<0.001, respectively). Both IL-4 and IL-13 significantly inhibited TNF induced IL-6 release (P<0.01 for both) while augmenting the effect of IFNgamma (P<0.005 and P<0.01, respectively.). IL-10 was without a significant effect. We conclude that Th2-type cytokines IL-4 and IL-13 affect the release of IL-6 by HBECs in response to TNFalpha (inhibition) and IFgamma (augmentation). IL-10 had no effect on the regulation of IL-6 release. Modulation of IL-6 levels by Th2-type cytokines may play a role in allergic reactions through the IL-6 promoting effect on IL-4 mediated IgE production.
Asunto(s)
Bronquios/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Interleucina-13/farmacología , Interleucina-4/farmacología , Interleucina-6/biosíntesis , Células Th2/inmunología , Bronquios/metabolismo , Células Cultivadas , Medio de Cultivo Libre de Suero , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales/metabolismo , HumanosRESUMEN
The aim of this study was to compare the alloreactive responses against HLA antigens of cord blood cells with those of adult peripheral blood cells. In primary mixed lymphocyte cultures and bulk cell-mediated lympholysis experiments cord blood cells demonstrated significantly decreased proliferation and cytotoxicity. Experiments analyzing the specificity of anti-HLA cytotoxic T lymphocytes (CTL) revealed that cord blood (CB) CTL reacted only partially with third-party cells expressing the stimulating HLA antigens. Lower frequencies of IL-2 producing helper, cytotoxic T-cell precursors and IL-4 producing CB cells were found, whereas the frequencies of IFN-gamma producing cells, as determined by ELISpot experiments, were equivalent to the frequencies of adult IFN-gamma producing cells. Our results imply that, although CB cells have significantly decreased proliferative and cytotoxic alloresponses in bulk mixed lymphocyte cultures, their IFN-gamma production is comparable with that of adult mononuclear cells. Preserved production of IFN-gamma may be a risk factor for the development of graft-versus-host disease and should be taken into consideration when evaluating the possibility for stem cell transplantation with HLA-mismatched CB.