Genetic factors, especially those related to immune system functioning, have been intensively studied to determine their role in the development of recurrent aphthous stomatitis (RAS). The aim of the present study was to analyze gene variability in interleukin (IL)2, IL4 (and its receptor α, IL4Rα), IL10, and IL13, which were selected based on literature review and/or their functional relevance, in Czech patients with RAS and in healthy controls. In total, 252 subjects (178 controls and 74 patients with RAS) were enrolled in this case-control study, and their detailed anamnestic, clinical, and laboratory data were obtained. Nine polymorphisms in the genes encoding interleukins were determined using PCR techniques. There were no significant differences in allele or genotype frequencies of the IL2, IL4, IL4Rα, IL10, and IL13 polymorphisms rs2069762/rs2069763, rs2243250/rs79071878, rs1801275, rs1800896, and rs1800925, respectively, between controls and patients with RAS. The minority alleles rs1800871 and rs1800872, which encode variants of IL10, were associated with a statistically significantly higher risk of RAS, as confirmed by the results of genotype and haplotype analyses. We suggest that variability in the IL10 gene may play an important role in the development of RAS in the Czech population.
- Klíčová slova
- association studies, candidate gene, genetic, immunity, oral ulcer, polymorphisms,
- MeSH
- aftózní stomatitida epidemiologie imunologie MeSH
- alely MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetická variace * MeSH
- genotyp MeSH
- haplotypy MeSH
- interleukin-10 genetika metabolismus MeSH
- interleukin-13 genetika metabolismus MeSH
- interleukin-2 genetika MeSH
- interleukin-4 genetika metabolismus MeSH
- interleukiny genetika metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- molekulární epidemiologie * MeSH
- polymerázová řetězová reakce MeSH
- polymorfismus genetický MeSH
- receptor interleukinu-4 - alfa-podjednotka genetika metabolismus MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Česká republika epidemiologie MeSH
- Názvy látek
- IL10 protein, human MeSH Prohlížeč
- IL2 protein, human MeSH Prohlížeč
- IL4 protein, human MeSH Prohlížeč
- IL4R protein, human MeSH Prohlížeč
- interleukin-10 MeSH
- interleukin-13 MeSH
- interleukin-2 MeSH
- interleukin-4 MeSH
- interleukiny MeSH
- receptor interleukinu-4 - alfa-podjednotka MeSH
PURPOSE: PFAPA syndrome is a benign, recurrent inflammatory disease of childhood. Tonsillectomy is one of the therapeutic options with a yet unexplained biological mechanism. We tested whether specific lymphocyte subsets recruited from blood to human tonsils participate in PFAPA pathogenesis. METHODS: Paired tonsils/peripheral blood (PB) samples were investigated (a) from children with PFAPA that successfully resolved after tonsillectomy (n=10) (b) from children with obstructive sleep apnoea syndrome as controls (n=10). The lymphocyte profiles were analysed using 8-colour flow cytometry, immunoglobulin (IGH) and T-cell receptor (TCR) gene rearrangements via PCR and next generation sequencing; a TREC/KREC analysis was performed using qPCR. RESULTS: The PFAPA tonsils in the asymptomatic phase had a lower percentage of B-lymphocytes than controls; T-lymphocyte counts were significantly higher in PB. The percentages of cytotoxic CD8pos T-lymphocytes were approximately 2-fold higher in PFAPA tonsils; the transitional B cells and naïve stages of both the CD4pos and CD8pos T-lymphocytes with a low expression of PD-1 molecule and high numbers of TREC were also increased. With the exception of elevated plasmablasts, no other differences were significant in PB. The expression levels of CXCL10, CXCL9 and CCL19 genes were significantly higher in PFAPA tonsils. The IGH/TCR pattern showed no clonal/oligoclonal expansion. DNA from the Epstein-Barr virus, Human Herpervirus-6 or adenovirus was detected in 7 of 10 PFAPA tonsils but also in 7 of 9 controls. CONCLUSIONS: Our findings suggest that the uninhibited, polyclonal response of newly derived lymphocytes participate in the pathogenesis of PFAPA. Because most of the observed changes were restricted to tonsils and were not present in PB, they partly explain the therapeutic success of tonsillectomy in PFAPA syndrome.
- Klíčová slova
- Autoinflammatory disease, Chemokine, Flow cytometry, KREC, PD-1, PFAPA, T lymphocyte, T-cell receptor gene rearrangement, TREC, Tonsillectomy,
- MeSH
- Adenoviridae genetika izolace a purifikace MeSH
- aftózní stomatitida komplikace imunologie chirurgie MeSH
- antigeny CD279 biosyntéza MeSH
- B-lymfocyty imunologie MeSH
- CD8-pozitivní T-lymfocyty imunologie MeSH
- chemokin CCL19 biosyntéza MeSH
- chemokin CXCL10 biosyntéza MeSH
- chemokin CXCL9 biosyntéza MeSH
- dítě MeSH
- faryngitida komplikace imunologie chirurgie MeSH
- horečka neznámého původu komplikace imunologie chirurgie MeSH
- kojenec MeSH
- krční mandle cytologie imunologie chirurgie MeSH
- lidé MeSH
- lidský herpesvirus 6 genetika izolace a purifikace MeSH
- lymfadenitida komplikace imunologie chirurgie MeSH
- obstrukční spánková apnoe imunologie chirurgie MeSH
- počet lymfocytů MeSH
- předškolní dítě MeSH
- receptory antigenů T-buněk genetika MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- tonzilektomie MeSH
- virus Epsteinův-Barrové genetika izolace a purifikace MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigeny CD279 MeSH
- CCL19 protein, human MeSH Prohlížeč
- chemokin CCL19 MeSH
- chemokin CXCL10 MeSH
- chemokin CXCL9 MeSH
- CXCL10 protein, human MeSH Prohlížeč
- CXCL9 protein, human MeSH Prohlížeč
- PDCD1 protein, human MeSH Prohlížeč
- receptory antigenů T-buněk MeSH
- MeSH
- aftózní stomatitida imunologie MeSH
- HLA antigeny analýza MeSH
- lidé MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- HLA antigeny MeSH
- MeSH
- aftózní stomatitida imunologie MeSH
- aktivace lymfocytů účinky léků MeSH
- kyselina listová farmakologie MeSH
- lidé MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- kyselina listová MeSH
- MeSH
- aftózní stomatitida imunologie MeSH
- aktivace lymfocytů * MeSH
- imunoglobuliny analýza MeSH
- lidé MeSH
- recidiva MeSH
- tuberkulinový test MeSH
- tvorba rozet * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH
- Názvy látek
- imunoglobuliny MeSH
- MeSH
- aftózní stomatitida imunologie MeSH
- celiakie imunologie MeSH
- Crohnova nemoc imunologie MeSH
- gastritida imunologie MeSH
- gastrointestinální nemoci imunologie MeSH
- lidé MeSH
- perniciózní anemie imunologie MeSH
- Sjögrenův syndrom imunologie MeSH
- ulcerózní kolitida imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- anglický abstrakt MeSH
- časopisecké články MeSH