Comprehensive analysis of tonsillar gene expression and the tonsillar microbiota in patients with palmoplantar pustulosis and pustulotic arthro-osteitis

BACKGROUND: Tonsillectomy improves symptoms in patients with palmoplantar pustulosis (PPP) and suppresses disease progression in patients with pustulotic arthro-osteitis (PAO), highlighting the important role of tonsils in the pathogenesis of PPP/PAO. OBJECTIVE: To identify inflammatory pathways involved in the tonsil tissue of patients with PPP/PAO, and to clarify the characteristics of tonsillar microbiota. METHODS: We assessed gene expression in tonsil tissue obtained from PPP/PAO or recurrent tonsillitis (RT)/sleep apnea syndrome (SAS) patients using microarray and quantitative reverse transcription polymerase chain reaction analysis. We also performed a comprehensive analysis of the tonsillar microbiota using next-generation sequencing. Potential associations between tonsillar gene expression and bacterial composition or disease activities were evaluated. RESULTS: Twenty-five tonsils from PPP/PAO patients and 15 tonsils from RT/SAS patients were included. The gene expression of inflammatory cytokines and molecules involved in the Th17, Th2, and Treg pathways was significantly higher in PPP/PAO tonsils than in RT/SAS tonsils. A significant positive correlation between Streptococcus spp. and the expression of Th17 and Th2 pathway genes was revealed both in PPP/PAO and RT/SAS, however, different correlation patterns were observed between these groups for the other genera. PAO disease activity showed a negative correlation with the expression of CCR4, FOXP3, and CXCR3 genes. CONCLUSION: PPP/PAO tonsils exhibit enhanced Th17, Th2, and Treg responses relative to RT/SAS, indicating a complex inflammatory condition. Streptococcus genus may be associated with inflammation, and interaction between microbiota and T cell immunity would be suggested in PPP/PAO tonsils. PAO disease activity inversely correlated with Treg response.