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Exploring the immunological basis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: immunohistochemical staining features of palatine tonsils

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Abstract

Objectives

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common periodic fever syndrome during early childhood period with regular febrile attacks of sterile upper airway inflammation. The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily. The aim of this study is to explore the immunological basis of PFAPA by evaluating the cellular properties of tonsils, and microbial exposition such as Helicobacter pylori on tonsillectomy materials.

Methods

The paraffinized tonsil samples of 26 PFAPA and 29 control patients with obstructive upper airway disorder were compared in terms of immunohistochemical staining features including CD4, CD8, CD123, CD1a, CD20, and H. pylori.

Results

The median number of CD8+ cells was 1485 (1218-1287) in PFAPA while it was 1003 (852–1261.5) in control group and the difference was statistically significant (p=0.001). Similarly, CD4+ cell counts were statistically higher in PFAPA group than control (833.5 vs 622). The ratio of CD4/CD8 did not differ between two groups; also, there was no statistically difference in terms of the other immunohistochemical staining results, such as CD20, CD1a, CD123 and H. pylori.

Conclusion

This is the largest number of pediatric tonsillar tissue study of PFAPA patients in current literature and we emphasized the triggering effects of CD8+ and CD4+ T-cells on PFAPA tonsils.

Key Points:

• The cessation of attacks following tonsillectomy points to fundamental role of tonsil tissue on etiopathogenesis of disease, which is not clarified satisfactorily.

• In current study, 92.3% of our patients did not experience any attacks following operation similarly with literature.

• We observed the increased number of CD4+ and CD8+ T cell counts on PFAPA tonsils compared to control group and emphasized the active role of both CD4+ and CD8+ cells localized on PFAPA tonsils in immune dysregulation.

• Some other cell types evaluated in this study such as CD19+ (B cells), CD1a (dendritic cells), and CD123 (IL-3 receptors, for pluripotent stem cells) and H. pylori did not differ in PFAPA patients compared to the control group.

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Abbreviations

PFAPA:

Periodic fever, aphthous stomatitis, pharyngitis, and adenitis

H. pylori :

Helicobacter pylori

SAA:

Serum amiloid A

CD:

Cluster of differentiation

CXCL:

C-X-C motif ligand

CCL:

C-C motif ligand

PD-1:

Programmed cell death protein

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Funding

This study funded by Dokuz Eylul University, Department of Scientific Research Project.

Author information

Authors and Affiliations

  1. Department of Pediatric Rheumatology, Dokuz Eylul University, Izmir, Turkey

    Serkan Türkuçar, Erbil Ünsal & Balahan Makay

  2. Division of Pediatric Rheumatology, Konya City Hospital, Karatay/Konya, Turkey

    Serkan Türkuçar

  3. Department of Medical Pathology, Dokuz Eylul University, Izmir, Turkey

    Göksenil Bülbül & Erdener Özer

  4. Department of Otorhinolaryngology, Dokuz Eylul University, Izmir, Turkey

    Taner Kemal Erdağ & Erdal Erkoç

Authors
  1. Serkan Türkuçar
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  2. Göksenil Bülbül
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  3. Erbil Ünsal
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  4. Erdener Özer
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  5. Taner Kemal Erdağ
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  6. Erdal Erkoç
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  7. Balahan Makay
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Contributions

• Design: Serkan Türkuçar, Balahan Makay, Erbil Ünsal, Erdener Özer, Taner Kemal Erdağ.

• Data collection: Serkan Türkuçar, Göksenil Bülbül, Erdal Erkoç.

• Sources: Balahan Makay, Serkan Türkuçar.

• Writing: Serkan Türkuçar, Erbil Ünsal, Balahan Makay, Taner Kemal Erdağ, Göksenil Bülbül.

• Critical review: Erbil Ünsal, Balahan Makay, Taner Kemal Erdağ, Erdener Özer.

Corresponding author

Correspondence to Serkan Türkuçar.

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Ethical approval

The ethical approval was obtained from Dokuz Eylul University Ethics Committee with number 2020/02-19 prior to the study.

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This was a retrospective designed study, so informed consent forms were not applied.

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Türkuçar, S., Bülbül, G., Ünsal, E. et al. Exploring the immunological basis of periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome: immunohistochemical staining features of palatine tonsils. Clin Rheumatol 42, 1911–1916 (2023). https://doi.org/10.1007/s10067-023-06563-2

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  • DOI: https://doi.org/10.1007/s10067-023-06563-2

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