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.
- MeSH
- alely MeSH
- atopická dermatitida genetika MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- haplotypy genetika MeSH
- interleukiny genetika MeSH
- jednonukleotidový polymorfismus MeSH
- kojenec MeSH
- lidé MeSH
- následné studie MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- progrese nemoci MeSH
- prospektivní studie MeSH
- sezónní alergická rýma genetika MeSH
- studie případů a kontrol MeSH
- TNF-alfa genetika MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
Toll-like receptors (TLR) are key components of innate immune system. As TLR activation could induce potentially harmful inflammatory response, activation of TLR signaling pathways has to be under tight control. Besides other control mechanisms, an inhibitory function of murine TLR4 splice variants was recently demonstrated. In this study we investigated expression of four TLR4 splice variants in human antigen presenting cells (APC). Furthermore, we studied modification in TLR4 splice variants expression in APC in cystic fibrosis (CF) patients chronically infected by Gram-negative bacteria. We developed a novel reliable real-time PCR detection system that allowed monitoring of individual TLR4 splice variants expression. In APC from healthy donors we detected a characteristic transient increase of two out of four splice variants after lipopolysaccharide (LPS) stimulation. Similarly to murine TLR4, one of these variants, NM 003266, might translate to a potentially inhibitory protein. In contrast to controls, CF monocytes had significantly changed LPS-induced expression of TLR4 gene and its variants including reduced ability to up-regulate the expression of the potentially inhibitory variant upon stimulation. In accordance with this observation, monocytes from CF patients produced significantly more tumor necrosis factor after LPS stimulation than healthy controls. Our results thus describe the kinetics of TLR4 splicing variants expression after LPS stimulation and indicate a possible alteration of its regulation in CF patients.
- MeSH
- alternativní sestřih MeSH
- antigen prezentující buňky chemie imunologie MeSH
- cystická fibróza imunologie MeSH
- dendritické buňky imunologie MeSH
- dospělí MeSH
- financování organizované MeSH
- kultivované buňky MeSH
- lidé MeSH
- lipopolysacharidy imunologie MeSH
- messenger RNA analýza MeSH
- monocyty imunologie MeSH
- polymerázová řetězová reakce s reverzní transkripcí metody MeSH
- regulace genové exprese MeSH
- stanovení celkové genové exprese MeSH
- TNF-alfa biosyntéza MeSH
- toll-like receptor 4 biosyntéza genetika MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
