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

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