Polyclonal, newly derived T cells with low expression of inhibitory molecule PD-1 in tonsils define the phenotype of lymphocytes in children with Periodic Fever, Aphtous Stomatitis, Pharyngitis and Adenitis (PFAPA) syndrome
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25656804
DOI
10.1016/j.molimm.2015.01.004
PII: S0161-5890(15)00006-1
Knihovny.cz E-resources
- Keywords
- Autoinflammatory disease, Chemokine, Flow cytometry, KREC, PD-1, PFAPA, T lymphocyte, T-cell receptor gene rearrangement, TREC, Tonsillectomy,
- MeSH
- Adenoviridae genetics isolation & purification MeSH
- Stomatitis, Aphthous complications immunology surgery MeSH
- Programmed Cell Death 1 Receptor biosynthesis MeSH
- B-Lymphocytes immunology MeSH
- CD8-Positive T-Lymphocytes immunology MeSH
- Chemokine CCL19 biosynthesis MeSH
- Chemokine CXCL10 biosynthesis MeSH
- Chemokine CXCL9 biosynthesis MeSH
- Child MeSH
- Pharyngitis complications immunology surgery MeSH
- Fever of Unknown Origin complications immunology surgery MeSH
- Infant MeSH
- Palatine Tonsil cytology immunology surgery MeSH
- Humans MeSH
- Herpesvirus 6, Human genetics isolation & purification MeSH
- Lymphadenitis complications immunology surgery MeSH
- Sleep Apnea, Obstructive immunology surgery MeSH
- Lymphocyte Count MeSH
- Child, Preschool MeSH
- Receptors, Antigen, T-Cell genetics MeSH
- T-Lymphocyte Subsets immunology MeSH
- Tonsillectomy MeSH
- Herpesvirus 4, Human genetics isolation & purification MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Programmed Cell Death 1 Receptor MeSH
- CCL19 protein, human MeSH Browser
- Chemokine CCL19 MeSH
- Chemokine CXCL10 MeSH
- Chemokine CXCL9 MeSH
- CXCL10 protein, human MeSH Browser
- CXCL9 protein, human MeSH Browser
- PDCD1 protein, human MeSH Browser
- Receptors, Antigen, T-Cell 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.
Mol Immunol. 2015 Aug;66(2):428 PubMed Petra, Dytrych; Petra, Krol; Michaela, Kotrova; Daniela, Kuzilkova; Petr, Hubacek; Ladislav, Krol; Rami, Katra; Ondrej, Hrusak; Zdenek, Kabelka; Pavla, Dolezalova; Tomas, Kalina; Eva, Fronkova [Corrected to Dytrych, Petra; Krol, Petra; Kotrova, Michaela; K
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