The first proteomics analysis of tonsils in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA)

Fatih Mutlu; Murat Kasap; Busra Yaprak Bayrak; Mehmet Sarıhan; Nihal Şahin; Alperen Önal; Gürler Akpınar; Yunus Emre Bayrak; Hafize Emine Sönmez

doi:10.1038/s41390-024-03741-z

The first proteomics analysis of tonsils in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis syndrome (PFAPA)

Pediatr Res. 2024 Nov 29. doi: 10.1038/s41390-024-03741-z. Online ahead of print.

Authors

Fatih Mutlu¹, Murat Kasap², Busra Yaprak Bayrak³, Mehmet Sarıhan², Nihal Şahin⁴, Alperen Önal¹, Gürler Akpınar², Yunus Emre Bayrak⁴, Hafize Emine Sönmez⁵

Affiliations

¹ Department of Otorhinolaryngology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
² Department of Basic Medical Sciences, Medical Biology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
³ Department of Pathology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
⁴ Department of Pediatrics, Division of Pediatric Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey.
⁵ Department of Pediatrics, Division of Pediatric Rheumatology, Kocaeli University Faculty of Medicine, Kocaeli, Turkey. eminesonmez@gmail.com.

PMID: 39613831
DOI: 10.1038/s41390-024-03741-z

Abstract

Background: Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is a recurrent fever syndrome. The exact etiopathogenesis of PFAPA syndrome remains unknown. Biological fluids or tissues may provide disease-specific biomarkers that may help clinicians to find new pathogenic pathways.

Methods: Tonsil tissues of seven patients with PFAPA were collected during the tonsillectomy. Seven patients who underwent tonsillectomy for reasons other than chronic tonsillitis were enrolled as a control group. The nHPLC LC-MS/MS system was used for protein identification and label-free quantification. Bioinformatics analysis was carried out using the UniProt accession numbers of the identified proteins.

Results: Proteomics analysis revealed to identity of proteins of which at least 23 were up and 57 were downregulated. Bioinformatics analysis of differentially regulated proteins by STRING indicated that protein folding and clearance machinery were interrupted in PFAPA patients compared to the controls. The affected pathways underlined the importance of the mitochondrial electron transport chain and ATP biosynthesis process.

Conclusion: Although it is not clear that changes in tonsil protein expression whether directly related to pathogenesis or simply result of chronic inflammation, the identification of tonsil biomarkers for PFAPA may provide clinicians an opportunity to understand disease pathogenesis or develop new molecular targets for treatments.

Impact: Proteomics analyses of tonsils revealed the identity of 80 proteins of which at least 23 were up and 57 were downregulated. Bioinformatics analysis underlined the importance of mitochondrial ETC and regulation of ATP biosynthetic process. This is the first study evaluating the proteomics of the tonsils of PFAPA patients. The identification of tonsil biomarkers for PFAPA may provide clinicians an opportunity to understand disease pathogenesis or develop new molecular targets for treatments.