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.

• 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