Increased levels of S100A8/A9, IL-1ß and IL-18 as a novel biomarker for recurrent tonsillitis

Abstract

Background: Acute tonsillitis represents one of the most frequent reasons patients seek primary medical care and otorhinolaryngology consultation. Therefore, recurrent episodes of acute tonsillitis (RAT), also called chronic tonsillitis, exhaust a substantial amount of medical and financial resources. Diagnosis of tonsillitis depends on a physical examination, which therefore does not allow for a reliable differentiation between viral and bacterial infection. However, the frequency of bacterial infections during the previous three years is currently being used as the major deciding factor in patient selection for tonsillectomy. The aim of the present study was to determine an objective biomarker to help in the identification of patients suffering from recurrent tonsillitis.

Results: By analyzing a panel of cytokines and chemokines in serum and saliva of patients with RAT compared to healthy controls, increased levels of IL-1ß (153.7 ± 48.5 pg/ml vs 23.3 ± 6.6 pg/ml, p = 0.021), IL-18 (120.2 ± 16.5 vs 50.6 ± 9.3 pg/ml, p = 0.007) and/or S100A8/A9 (996 ± 102 ng/ml vs 546 ± 86 ng/ml, p = 0.042) could be observed in patients suffering from RAT. Cut-off values of these parameters were determined and combined to a new RAT-score allowing for reliable identification of patients suffering from recurrent tonsillitis with a sensitivity of 95% and a specificity of 88%.

Conclusion: The RAT-score represents the first objective criterion as a tool for the diagnosis of recurrent tonsillitis and it also improves patient selection for tonsillectomy.

Keywords: Biomarker; Calprotectin; Diagnosis; Interleukin; Recurrent tonsillitis.

Fig. 1

Cytokine levels of IL-33 (A), IFN-α (B), IFN-γ (C), TNF-α (D), MCP-1 (E), IL-6 (F), IL-8 (G), IL-10 (H), IL-12p70 (I), IL-17 (J), IL-18 (K) and IL-1ß (L) in saliva. Levels of IL-1ß, IL-6, TNF-α and IL-33 are significantly increased in patients with recurrent tonsillitis (RAT) compared to healthy controls (*p < 0.05). All values are given in [pg/ml]

Fig. 2

Cytokine levels of IL-18 (A), IFN-α (B), IFN-γ (C), TNF-α (D), MCP-1 (E), IL-1ß (F), IL-6 (G), IL-8 (H), IL-10 (I), IL-12p70 (J), IL-17 (K) and IL-33 (L) in serum. Significantly increased levels of IL-18 could be observed in patients with recurrent tonsillitis (RAT) compared to healthy controls (**p < 0.01). All values are given in [pg/ml]

Fig. 3

S100A8/A9 levels in serum (A) and saliva (B) of patients with recurrent tonsillitis (RAT) compared to healthy controls (*p < 0.05)

Fig. 4

Receiver Operating Characteristic curve analysis of the RAT score. A cut-off value of 1.5 could be determined for the RAT score in order to identify patients with recurrent tonsillitis with a sensitivity of 0.95 and a specificity of 0.88. Area under the curve A = 0.959