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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

Petra, Dytrych ; Petra, Krol ; Michaela, Kotrova ; Daniela, Kuzilkova ; Petr, Hubacek ; Ladislav, Krol LU orcid ; Rami, Katra ; Ondrej, Hrusak ; Zdenek, Kabelka and Pavla, Dolezalova , et al. (2015) In Molecular Immunology 65(1). p.139-147
Abstract

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... (More)

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.

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type
Contribution to journal
publication status
published
subject
keywords
Autoinflammatory disease, Chemokine, Flow cytometry, KREC, PD-1, PFAPA, T lymphocyte, T-cell receptor gene rearrangement, Tonsillectomy, TREC
in
Molecular Immunology
volume
65
issue
1
pages
139 - 147
publisher
Pergamon Press Ltd.
external identifiers
  • scopus:84921951883
  • pmid:25656804
ISSN
0161-5890
DOI
10.1016/j.molimm.2015.01.004
language
English
LU publication?
no
additional info
Funding Information: This work was supported by GAUK 266411. T.K. and J.T. were supported by the GAČR Centre of Excellence P302/12/G101. E.F. received the ĹOreal for Women in Science Fellowship in 2013. M.K. was supported by IGA NT/14343-3. We thank Jan Stuchly for help with the data analysis. The authors are most grateful to doc. Zdeněk Kabelka, Ph. D. (passed away on 24 March 2014) for his expertise and invaluable help with all aspects of the study. The authors wish to dedicate this paper to his memory. Publisher Copyright: © 2015 Elsevier Ltd. Copyright: Copyright 2019 Elsevier B.V., All rights reserved.
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99ddc62b-885d-4ee5-b816-4c073fa85704
date added to LUP
2021-04-29 08:14:42
date last changed
2024-06-01 10:37:34
@article{99ddc62b-885d-4ee5-b816-4c073fa85704,
  abstract     = {{<p>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.</p>}},
  author       = {{Petra, Dytrych and Petra, Krol and Michaela, Kotrova and Daniela, Kuzilkova and Petr, Hubacek and Ladislav, Krol and Rami, Katra and Ondrej, Hrusak and Zdenek, Kabelka and Pavla, Dolezalova and Tomas, Kalina and Eva, Fronkova}},
  issn         = {{0161-5890}},
  keywords     = {{Autoinflammatory disease; Chemokine; Flow cytometry; KREC; PD-1; PFAPA; T lymphocyte; T-cell receptor gene rearrangement; Tonsillectomy; TREC}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{139--147}},
  publisher    = {{Pergamon Press Ltd.}},
  series       = {{Molecular Immunology}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1016/j.molimm.2015.01.004}},
  doi          = {{10.1016/j.molimm.2015.01.004}},
  volume       = {{65}},
  year         = {{2015}},
}