Miscellanea. Folyóirat-referátumok. Könyvismertetés

Folyóirat-referátumok. Hepatológia A gyermekkori autoimmun májbetegség diagnózisa és kezelése: az Európai Gyermekgasztroenterológiai Társaság (ESPGHAN) Hepatológiai Bizottságának állásfoglalása (Diagnosis and management of pediatric autoimmune liver disease: ESPGHAN Hepatology Committee position statement) Mieli-Vergani G, Vergani D, Baumann U, et al. (Pediatric Liver Centre, King’s College Hospital, Denmark Hill, London SE5 9RS, Egyesült Királyság; e-mail: [email protected]):J Pediatr Gastroenterol Nutr (JPGN) 2018; 66: 354–360. | Kölcsönhatás az alkoholfogyasztás és a metabolikus szindróma között a súlyos májbetegség előrejelzésében az általános népességben (Interaction between alcohol consumption and metabolic syndrome in predicting severe liver disease in the general population)Åberg F, Helenius-Hietala J, Puukka P, et al. (HUCH Meilahti Hospital, PB 372, 00029 Hus, Finnország; e-mail: [email protected]):Hepatology 2018; 67: 2141–2149. | Infektológia Pneumococcusbacteriaemia és meningitis (Pneumococcal bacteremia and meningitis) Mora Carpio AL, Stempel JM. (Albert Einstein Medical Center, 5501 Old York Rd, Philadelphia, PA 19141, Amerikai Egyesült Államok;e-mail: [email protected]):N Engl J Med. 2018; 379: 2063. | Könyvismertetés. AJÁNLÓ Bősze Péter„Magyar orvosi nyelv – Nyelvhasználati megfontolások” és„Magyar orvosi nyelv – Helyesírási útmutató” című könyveihe

Involvement of heat shock proteins in gluten-sensitive enteropathy

Gluten-sensitive enteropathy, also known as coeliac disease (CD), is an autoimmune disorder occurring in genetically susceptible individuals that damages the small intestine and interferes with the absorption of other nutrients. As it is triggered by dietary gluten and related prolamins present in wheat, rye and barley, the accepted treatment for CD is a strict gluten-free diet. However, a complete exclusion of gluten-containing cereals from the diet is often difficult, and new therapeutic strategies are urgently needed. A class of proteins that have already emerged as drug targets for other autoimmune diseases are the heat shock proteins (HSPs), which are highly conserved stress-induced chaperones that protect cells against harmful extracellular factors. HSPs are expressed in several tissues, including the gastrointestinal tract, and their levels are significantly increased under stress circumstances. HSPs exert immunomodulatory effects, and also play a crucial role in the maintenance of epithelial cell structure and function, as they are responsible for adequate protein folding, influence the degradation of proteins and cell repair processes after damage, and modulate cell signalling, cell proliferation and apoptosis. The present review discusses the involvement of HSPs in the pathophysiology of CD. Furthermore, HSPs may represent a useful therapeutic target for the treatment of CD due to the cytoprotective, immunomodulatory, and anti-apoptotic effects in the intestinal mucosal barrier

Altered mitochondrial response to activation of T-cells in neonate

Mitochondrial functions have a major impact on T-cell functionality. In this study we characterized whether mitochondrial function in the neonatal T-cells differs from that in the adult T-cells during short T-cell activation. METHODS: We used fow cytometry methods to test mitochondrial mass and to monitor mitochondrial Ca(2+) levels, mitochondrial potential and superoxide generation in parallel with cytoplasmic Ca(2+) levels during phythohaemagglutinine-induced activation of CD4+ and CD8+ T-cells of 12 term neonates and 11 healthy adults. RESULTS: Baseline mitochondrial mass of CD4+ and CD8+ cells was lower in the neonate than in the adult. In comparison with the adult, neonatal resting CD4+ T-cells had lower cytoplasmic Ca(2+) levels and this was associated with normal activation induced Ca(2+)-response. During short-term activation cytoplasmic Ca(2+)-response was lower in neonatal than in adult CD8+ T-cells. Mitochondrial Ca(2+) uptake was increased in CD4+ neonatal T cells while it decreased in CD8+ T-cells. Mitochondrial depolarization was increased in CD4+ and decreased in CD8+ neonatal T-cells compared to adults. Superoxide generation was higher and equal in neonatal CD4+ and CD8+ cells, respectively, compared to the adult ones. CONCLUSION: Our data suggest that neonatal T-cells exhibit marked differences in mitochondrial function and superoxide generation compared to adult T-cells

Expression of lymphocyte activation markers of preterm neonates is associated with perinatal complications

BACKGROUND: Inappropriate activation of T lymphocytes plays an important role in perinatal complications. However, data on T lymphocyte activation markers of preterm infants is scarce. We investigated the association between gender, gestational and postnatal age, preeclampsia (PE), premature rupture of membranes (PROM) as well as prenatal steroid treatment (PS) and the frequency of activated T lymphocyte subsets (HLA-DR+, CD69+, CD25+, CD62L+) and major T lymphocyte subpopulations (CD4, CD8, Th1, Th2, naive, memory) in peripheral blood during the first postnatal week in preterm infants. RESULTS: Cord blood and peripheral blood samples were collected from 43 preterm infants on the 1st, 3rd, and 7th days of life. We assessed the frequency of the above T lymphocyte subsets using flow cytometry. The 'mixed effect model' was used to analyze the effects of clinical parameters on T lymphocyte markers. The frequency of CD25+ T lymphocytes was higher in PROM. The frequency of CD4+ and CD8+ cells and the CD4+/CD8+ cell ratio was decreased in PE. The frequency of CD62L+ T lymphocytes was higher in male compared with female infants. PS did not affect the frequency of the investigated markers. CD4+ CD25+ cells had a lower frequency at birth than on day 7. Th2 lymphocytes had a lower frequency on postnatal days 1 and 3 when compared to day 7. CONCLUSIONS: Our observations indicate that alterations affecting the expression of T lymphocyte activation markers are associated with the above factors and may play a role in the development of perinatal complications

Koraszülöttek perinatális szövődményeinek előrejelzése: limfocita-aktiváció és biomarkerek = Prediction of perinatal complications in preterm infants: lymphocyte activation and biomarkers

Koraszülötteken elért eredményeink jelzik, hogy a veleszületett és szerzett immunitást számos, a koraszülöttséggel járó tényező befolyásolja. A citokinválaszt befolyásoló legfontosabb tényező a magzati korban fennálló gyulladás (chorioamnionitis, CA). CA hiányában a citokinek jellegzetes módon fluktuálnak; ezt a jelenséget figyelembe kell venni akkor, ha a perinatalis citokinszintekkel kapcsolatosan vizsgálatokra kerül sor. A fluktuáció CA jelenlétében teljes mértékben megszűnik. A citokinektől eltérően az adaptív immunválasz szabályozásában kulcsszerepet játszó CD4 és CD8 sejtek számát a CA nem befolyásolja. Ezzel szemben a mellékvese működése, valamint a postnatalis és a gesztációs kor egyaránt alapvető hatást gyakorol ezekre a sejtekre. A veleszületett immunitásért felelős sejtek esetében a postnatalis kor a fő meghatározó. Érdekes módon a vizsgált tényezők közül a magzatnál a tüdő érés érdekében adott anyai szteroidkezelés nem hatott az immunrendszerre. A pályázat időtartama alatt több új módszert vezettünk be az immunsejtek működésének a vizsgálatára. Ezek segítségével egyéb, az immunrendszer működési zavarával járó betegségek kutatásában is fontos eredményeket értünk el. | These results obtained in preterm neonates clearly indicate that the investigated elements of adaptive and innate immunity including cytokines and cellular players are influenced by a number of factors inherent with the premature birth. The major factor having a large impact on cytokine response is chorioamnionitis (CA). In the neonates without CA the measured cytokines presented a characteristic fluctuation. One should emphasize that there is some ’physiologic’ kinetics of postnatal cytokine expression in the preterm neonate that is masked in the presence of CA. This ’physiologic’ kinetics should be taken into account when any investigation on perinatal inflammation is performed. In contrast with cytokines CD4 and CD8 cells governing the adaptive immune responses of the neonates are not affected by CA. Instead, the prevalence of some subpopulations of CD4 and CD8 cells correlated with neonatal cortisol levels, and with postnatal and gestational age. The major determinant of the prevalence of innate immune cells is the postnatal age emphasizing that that the timing of postnatal blood sampling is essential when the innate immune response of a neonate is analyzed. Interestingly, maternal steroid therapy has no effect the neonate’s immune system. During the proposal we also made several achievements in different conditions where the immune dysregulation is dominantly present

A Th17 sejtek szerepe rheumatoid arthritisben

Th17 cells are the newly described subset of the CD4 + T lymphocytes. Activated Th17 cells are characterized by their ability to produce IL-17A and other pro-inflammatory cytokines. IL-17A regulates immune function through its cell- surface receptor expressed on epithelial-and endothelial cells, fibroblasts and leukocytes by promoting neutrophil recruitment and releasing further pro-inflammatory mediators. Failures of the susceptible balance of the immunoregulation may lead to unchecked immune response and autoimmune diseases. The central role of Th17 cells and cytokines produced by Th17 cells were confirmed in a wide variety of human autoimmune diseases, including rheumatoid arthritis. Recently Th17 cells and its cytokines come into the focus of immunological research as potential therapeutic targets

Hyperhomocysteinaemia and MTHFR C677T gene polymorphism in renal transplant recipients

Aim-To study the effect of folate treatment on hyperhomocysteinaemia and the effect of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism on total homocysteine and folate concentrations after renal transplantation. Methods-A total of 30 transplanted children and adolescents were investigated for total homocysteine and folate serum concentrations before and after folate treatment, as well as for the presence of the MTHFR C677T polymorphism. Results-The allele frequency of C677T polymorphism in the MTHFR gene in the study population (0.33) was not different to that in controls (0.38). Before folate treatment the homocysteine concentration was raised in all groups; following folate supplementation it was significantly decreased in the CC and CT groups, but not in the TT group. In patients with CC genotype, serum homocysteine correlated with serum creatinine and cholesterol, and time since transplantation before treatment. Conclusion-Folate supplementation appears to be an effective strategy to normalise total homocysteine concentration in renal transplanted children and adolescents