PATIENTS WITH PERIODIC FEVER, APHTHOUS STOMATITIS, PHARYNGITIS AND ADENITIS (PFAPA) SYNDROME HAVE ALTERED METHYLATION PATTERNS IN PIK3AP1 (BCAP) AND SPON2 (SPONDIN-2) GENES
- Ema Lovsin, Slovenia
Abstract
Background and Aims
Periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children, often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether a differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA versus healthy controls.
Methods
A whole epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, of which two were further evaluated with methylation specific restriction enzymes coupled with qPCR (MSRE-qPCR).
Results
The analysis showed that PIK3AP1 and SPON2 intronic gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable and cost-effective method to confirm results from MeDIP and MBD.
Conclusions
Our findings indicate that B cell adapter protein (BCAP) as PI3K binding inhibitor of inflammation and spondin-2 (SPON2) as a pattern recognition molecule and integrin ligand could play a role in etiology of PFAPA. Their role and impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.