Az intestinalis toll-like receptorok (TLR) expressziójának változásai és hatásuk az immunaktivációra immunpatogenezisű bélbetegségekben = Change of intestinal toll-like receptor expression an their effect on immune activation in immunopathogenetic intestinal diseases

A belek immunpatogenezisű kórképeinek kialakulásáért a természetes immunrendszer működési zavara is felelőssé tehető. Kutatásaink során arra a kérdésre kerestünk, hogy hogyan változik a TLR2, TLR3 és TLR4 expresszió coeliákiás gyermekek és krónikus gyulladásos bélbetegségben bélbiopsziás mintáiban a kontrollokhoz képest. Ugyancsak elemeztük, hogy a CD14, a TLR4 és a CARD15 polimorfizmusok (SNP) összefüggenek-e a nekrotizáló enterokolitisz (NEC) kialakulásával. A kezeletlen- és kezelt coeliákiás gyermekek duodenális nyálkahártyájában a TLR2 és TLR4 expresszió fokozódott a kontrollokhoz képest. Sőt, a kezelt coeliákiás gyermekek duodenális nyálkahártyájában még fokozottabb TLR2 és TLR4 expressziót volt kimutatható. A frissen diagnosztizált (fd)- és a relapszusban lévő (r) IBD-s gyermekek colon nyálkahártyájának gyulladásban lévő szakaszán szintén fokozódott a TLR2 és TLR4 expresszió. A colon nyálkahártya gyulladásban nem lévő szakaszán azonban, a TLR2 és TLR4 expresszió nem tért el a kontrollokétól, sem fdIBD-ben, sem rIBD-ben. A CD14 C-260T, TLR4 A+896G és C+1196T és a CARD15 G+2722C, C+2104T, és 3020insC SNP-k előfordulási gyakorisága nem különbözött a kis születési súlyú NEC-es illetve nem NEC-es koraszülöttek és az egészséges újszülöttek esetében Eredményeink arra utalnak, hogy a fokozott TLR2 és TLR4 expressziónak elsődleges szerepe lehet a coeliákia patogenezisében, míg szerepük IBD kialakulásában másodlagos. | Disturbances of innate immune responses may be responsible for the development of immunopathogenetic intestinal diseases. The aim of this study was to characterise how changes in the expression of TLR2, TLR3 and TLR4 in the intestinal samples taken from children with coeliac disease or (CD) with IBD compared to controls. Moreover, it was analysed whether how the SNPs of CD14, TLR4 and CARD15 genes are associated with the risk of necrotizing enterocolitis. TLR2 and TLR4 mRNA expression were higher in the duodenal mucosa of children with treated CD and untreated CD than in controls. TLR2 and TLR4 mRNA expression and protein levels were even higher in the duodenal mucosa of children with treated CD than in untreated CD. TLR2 and TLR4 mRNA expression and protein levels were higher in the inflammed colonic mucosa of children with freshly diagnosed (fd) IBD and relapsed (r) IBD compared to controls. In the non inflammed colonic mucosa of children with fdIBD and rIBD, TLR2 and TLR4 mRNA expression and protein levels were similar to controls. No significant differences were found in the prevalence of CD14 -260T, TLR4 +896G and +1196T and CARD15 +2722C, +2104T and 3020insC alleles between WLBW infants -with and without NEC. The increased expression of TLR2 and TLR4 even in treated CD may indicate their primary role in the pathomechanism of CD, while their role is secondary in the development of IBD

Foreign body impaction in the sigmoid colon

Foreign body ingestion is a common clinical problem in early childhood. However, it may occur even in adults, unknowingly. Most ingested foreign bodies entering the stomach pass through the gastrointestinal tract uneventfully. Here we report on a 13-year-old boy who presented with chronic abdominal pain, weight loss and occult gastrointestinal bleeding for 6 mo. Colonoscopy was negative; however, a ballpoint pen was impacted in the sigmoid region. Subsequently, the child admitted swallowing a pen as a 20-euro bet 6 mo previously. Crohn's disease is a chronic relapsing inflammatory gastrointestinal disease. It is often difficult to diagnose due to the fact that there is no single pathognomonic sign or symptom. This case is a description of an adolescent with chronic gastrointestinal symptoms due to a foreign body. Therefore, an ingested foreign body should be included in the differential diagnostic procedure related to gastrointestinal symptoms

Characteristics of allergic colitis in breast-fed infants in the absence of cow’s milk allergy

AIM: To investigate the characteristics of mucosal lesions and their relation to laboratory data and long-term follow up in breast-fed infants with allergic colitis. METHODS: In this study 31 breast-fed infants were prospectively evaluated (mean age, 17.4 wk) whose rectal bleeding had not ceased after a maternal elimination diet for cow's milk. Thirty-four age-matched and breast-fed infants (mean age, 16.9 wk) with no rectal bleeding were enrolled for laboratory testing as controls. Laboratory findings, colonoscopic and histological characteristics were prospectively evaluated in infants with rectal bleeding. Long-term follow-up with different nutritional regimes (L-amino-acid based formula or breastfeeding) was also included. RESULTS: Iron deficiency, peripheral eosinophilia and thrombocytosis were significantly higher in patients with allergic colitis in comparison to controls (8.4 ± 3.2 μmol/L vs 13.7 ± 4.7 μmol/L, P < 0.001; 0.67 ± 0.49 G/L vs 0.33 ± 0.17 G/L, P < 0.001; 474 ± 123 G/L vs 376 ± 89 G/L, P < 0.001, respectively). At colonoscopy, lymphonodular hyperplasia or aphthous ulceration were present in 83% of patients. Twenty-two patients were given L-amino acid-based formula and 8 continued the previous feeding. Time to cessation of rectal bleeding was shorter in the special formula feeding group (mean, 1.4 wk; range, 0.5-3 wk) when compared with the breast-feeding group (mean, 5.3 wk; range, 2-9 wk). Nevertheless, none of the patients exhibited rectal bleeding at the 3-mo visit irrespective of the type of feeding. Peripheral eosinophilia and cessation of rectal bleeding after administration of elemental formula correlated with a higher density of mucosal eosinophils. CONCLUSION: Infant hematochezia, after cow's milk allergy exclusion, is generally a benign and probably self-limiting disorder despite marked mucosal abnormality. Formula feeding results in shorter time to cessation of rectal bleeding; however, breast-feeding should not be discouraged in long-lasting hematochezia

A coeliakia genetikai es epigenetikai vonatkozasai.

Genetic backround of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications. Orv. Hetil., 2014, 155(3), 83-88

Immune phenotype in children with therapy-naïve remitted and relapsed Crohn’s disease

AIM To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy naive childhood Crohn s disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease METHODS We enrolled 26 pediatric patients with CD 14 therapy naive CD children, of those, 10 children remitted on conventional therapy and formed the re mission group We also tested another group of 12 children who relapsed with conventional therapy and were given infliximab, and 15 healthy children who served as controls The prevalence of Th1 and Th2, naive and memory, activated and regulatory T cells, along with the members of innate immunity such as natural killer (NK), NK T, myeloid and plasmocytoid dendritic cells (DCs), monocytes and Toll like receptor (TLR) 2 and TLR 4 expression were determined in peripheral blood samples RESULTS Children with therapy naive CD and those in relapse showed a decrease in Th1 cell prevalence Simultaneously, an increased prevalence of memory and activated lymphocytes along with that of DCs and monocytes was observed In addition, the ratio of myeloid/plasmocytoid DCs and the prevalence of TLR2 or TLR4 positive DCs and monocytes were also higher in therapy naive CD than in controls The majority of alterations diminished in remitted CD irrespective of whether remission was obtained by conventional or biological therapy CONCLUSION The finding that immune phenotype is normalized in remission suggests a link between immune phenotype and disease activity in childhood CD Our observations support the involvement of members of the adaptive and innate immune systems in childhood CD (C) 2010 Baishideng All rights reserve