Common genetic susceptibility loci link PFAPA syndrome, Behçet's disease, and recurrent aphthous stomatitis.

Proceedings of the National Academy of Sciences of the United States of America
Kalpana ManthiramDaniel L Kastner

Abstract

Periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis (PFAPA) syndrome is the most common periodic fever syndrome in children. The disease appears to cluster in families, but the pathogenesis is unknown. We queried two European-American cohorts and one Turkish cohort (total n = 231) of individuals with PFAPA for common variants previously associated with two other oropharyngeal ulcerative disorders, Behçet's disease and recurrent aphthous stomatitis. In a metaanalysis, we found that a variant upstream of IL12A (rs17753641) is strongly associated with PFAPA (OR 2.13, P = 6 × 10-9). We demonstrated that monocytes from individuals who are heterozygous or homozygous for this risk allele produce significantly higher levels of IL-12p70 upon IFN-γ and LPS stimulation than those from individuals without the risk allele. We also found that variants near STAT4, IL10, and CCR1-CCR3 were significant susceptibility loci for PFAPA, suggesting that the pathogenesis of PFAPA involves abnormal antigen-presenting cell function and T cell activity and polarization, thereby implicating both innate and adaptive immune responses at the oropharyngeal mucosa. Our results illustrate genetic similarities among recurrent aphthous stomat...Continue Reading

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Citations

Feb 16, 2021·Frontiers in Cellular and Infection Microbiology·Mysore V TejesviMarjo Renko
Feb 13, 2021·Postgraduate Medical Journal·Zihan WangZhensheng Cao
Feb 23, 2021·Frontiers in Medicine·Mehmet YildizOzgur Kasapcopur
Jun 8, 2021·Frontiers in Medicine·Gonca Mumcu, Farida Fortune
Jun 29, 2021·Frontiers in Pediatrics·Caterina Matucci-CerinicAngelo Ravelli

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Methods Mentioned

BETA
genotyping
ELISA
flow cytometry
chip

Software Mentioned

Immunochip
Haploview
HaploReg

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