Deciphering the Inflammatory Network in Pediatric Recurrent Tonsillitis: The Role of TRAF6, IRAK1, and miR-146a-5p.

OBJECTIVE: To investigate the role of TNF receptor-associated factor 6 (TRAF6), interleukin 1 receptor-associated kinase 1 (IRAK1), and miR-146a-5p expression levels in the pathogenesis of recurrent tonsillitis. STUDY DESIGN: Case-control study. SETTING: The study was conducted at the Department of Otorhinolaryngology, Muğla Training and Research Hospital, a tertiary referral center. METHODS: This study included 60 pediatric patients (aged 2-18 years) who underwent tonsillectomy according to American Academy of Otolaryngology-Head and Neck Surgery guidelines. 30 patients with recurrent tonsillitis were compared with 30 patients with tonsillar hypertrophy. Patients with chronic inflammatory diseases, recent steroid use, PFAPA syndrome, or asymmetric hypertrophy were excluded. Right palatine tonsil tissues were collected intraoperatively, and the mid-portion was analyzed. Expression levels of TRAF6, IRAK1, and miR-146a-5p were quantified using real-time polymerase chain reaction (qRT-PCR). In silico analyses evaluated related molecular pathways and target gene interactions. RESULTS: TRAF6 and IRAK1 mRNA levels were significantly increased in the recurrent tonsillitis group compared with controls (fold change: 1.64 and 1.43; P = .043 and P = .034, respectively), whereas miR-146a-5p expression was significantly decreased (2.17-fold; P = .012). Bioinformatic analysis identified nuclear factor kappa B (NF-κB), interleukin-1 (IL-1), and Toll-like receptor (TLR) signaling pathways. TRAF6, IRAK1, TLR4, epidermal growth factor receptor (EGFR), IL-6, and chemokine ligand 8 (CXCL8) were identified as potential miR-146a-5p targets. CONCLUSION: These findings suggest dysregulation of the TRAF6/IRAK1-miR-146a-5p axis in recurrent tonsillitis. While miR-146a-5p may represent a potential target within TLR/NF-κB-related pathways its therapeutic relevance remains speculative and requires validation through functional and translational studies.