Immunology of Pediatric Tonsil Disorders

National Institute Of Allergy And Infectious Diseases

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Abstract

Over the past 6 years, we have obtained tonsil samples from over 200 patients with PFAPA, obstructive sleep apnea (OSA), and controls with craniofacial anomalies. We analyzed the immune cell profile using flow cytometry, gene expression in particular cell populations, and function of particular cells with stimulation studies. Through our analyses of the tonsils, we found that sorted CD4+ T cells from the tonsils of patients with PFAPA have increased expression of Th1 and Th17-related genes. Moreover, upon stimulation with PMA and ionomycin, effector CD4+ T cells in the tonsils produce more IFN-gamma and IL-17 than those from controls undergoing tonsillectomy for anatomic craniofacial deformities. In addition, among myeloid cells in the tonsils and peripheral blood we saw downregulation of inflammatory genes during an asymptomatic period suggesting that the activation status of myeloid cells may oscillate with flare and non-flare periods. We have also found that OSA is an inflammatory disease of the palatine tonsils with enlarged germinal centers, more T follicular helper (Tfh) cells, and activated effector CD4+ T cells, CD8+ T cells, and NK cells. We also found that these patients have large germinal centers on histology assessment of the tonsils. We have also characterized clinical features and outcome of patients with pediatric tonsil disorders, particularly PFAPA syndrome. Although tonsillectomy resolves flares in most patients with PFAPA, we found that a portion did not respond fully to tonsillectomy and identified clinical features that could be used by clinicians to predict response and effective treatments for those with continued flares after tonsillectomy.