Innate immunity-related Gene Expression Profiling Reveals Two Distinct Endotypes in PFAPA Syndrome
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Mariko Hara, M.D., Noriko Morimoto, M.D., Kae Fujii, M.D., Sota Yamaguchi, M.D., Mayumi Tsunoda, M.D., Keisuke Yoshihama, M.D., Hideaki Morita, M.D., Ph.D., Kenji Matsumoto, MD PhD
RATIONALE: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. Elevated serum proinflammatory cytokine levels imply dysregulation of innate immunity in the pathogenesis of PFAPA. However, it remains unclear what types of innate immunity molecules/pathways are actually involved. Most PFAPA patients develop tonsillitis during febrile episodes, and tonsillectomy promptly and completely resolves the periodic fever. That fact suggests that the tonsils are the primary site of immune dysregulation in PFAPA. We evaluated the expression levels of innate immunity-related genes in the tonsils of children with PFAPA in order to identify the activated innate immunity molecules/pathways.

METHODS: Microarray analysis was performed to determine the expression levels of innate immunity-related genes (toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-like receptors (RLRs), C-type lectin-like receptors (CLRs), and DNA sensors) in tonsillar samples from 15 PFAPA children.

RESULTS: Expression profiling of tonsillar innate immunity-related genes revealed two distinct endotypes of PFAPA. Pathway and upstream analysis indicated that CLRs and plasmacytoid dendritic cell (pDC)-related genes were highly expressed in endotype 1, whereas macrophage-related genes such as TLR4 were highly expressed in endotype 2. Furthermore, endotypes 1and 2 differed in regard to the presence/absence of some clinical features.

CONCLUSIONS: Two distinct innate immunity molecules/pathways are likely to be involved in the pathogenesis of PFAPA. The precise molecular functions/mechanisms of these genes warrant further study.