PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children and is often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether differe...
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doaj-1a1055a107db4ea3a14a40e0fefc95452020-11-25T03:48:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01322540288PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) SyndromeEma Lovšin0Ema Lovšin1Jernej Kovač2Tine Tesovnik3Nataša Toplak4Nataša Toplak5Daša Perko6Tomaž Rozmarič7Maruša Debeljak8Maruša Debeljak9Tadej Avčin10Tadej Avčin11Department of Allergology, Rheumatology and Clinical Immunology, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment for Special Laboratory Diagnostics, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaDepartment for Special Laboratory Diagnostics, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaDepartment of Allergology, Rheumatology and Clinical Immunology, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment for Special Laboratory Diagnostics, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaDepartment of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, AustriaFaculty of Medicine, University of Ljubljana, Ljubljana, SloveniaDepartment for Special Laboratory Diagnostics, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaDepartment of Allergology, Rheumatology and Clinical Immunology, University Medical Centre Ljubljana, University Children's Hospital, Ljubljana, SloveniaFaculty of Medicine, University of Ljubljana, Ljubljana, SloveniaPeriodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children and is often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA vs. healthy controls. A whole-epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, two of which were further evaluated with methylation-specific restriction enzymes coupled with qPCR (MSRE-qPCR). The analysis showed that the PIK3AP1 and SPON2 gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable, and cost-effective method of confirming results from MeDIP and MBD. Our findings indicate that a B-cell adapter protein (PIK3AP1), as the PI3K binding inhibitor of inflammation, and spondin-2 (SPON2), as a pattern recognition molecule and integrin ligand, could play a role in the etiology of PFAPA. Their role and the impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation.https://www.frontiersin.org/article/10.3389/fimmu.2020.01322/fullPFAPAdifferential methylationPIK3AP1SPON2MSRE-qPCRMeDIP |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ema Lovšin Ema Lovšin Jernej Kovač Tine Tesovnik Nataša Toplak Nataša Toplak Daša Perko Tomaž Rozmarič Maruša Debeljak Maruša Debeljak Tadej Avčin Tadej Avčin |
spellingShingle |
Ema Lovšin Ema Lovšin Jernej Kovač Tine Tesovnik Nataša Toplak Nataša Toplak Daša Perko Tomaž Rozmarič Maruša Debeljak Maruša Debeljak Tadej Avčin Tadej Avčin PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome Frontiers in Immunology PFAPA differential methylation PIK3AP1 SPON2 MSRE-qPCR MeDIP |
author_facet |
Ema Lovšin Ema Lovšin Jernej Kovač Tine Tesovnik Nataša Toplak Nataša Toplak Daša Perko Tomaž Rozmarič Maruša Debeljak Maruša Debeljak Tadej Avčin Tadej Avčin |
author_sort |
Ema Lovšin |
title |
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome |
title_short |
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome |
title_full |
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome |
title_fullStr |
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome |
title_full_unstemmed |
PIK3AP1 and SPON2 Genes Are Differentially Methylated in Patients With Periodic Fever, Aphthous Stomatitis, Pharyngitis, and Adenitis (PFAPA) Syndrome |
title_sort |
pik3ap1 and spon2 genes are differentially methylated in patients with periodic fever, aphthous stomatitis, pharyngitis, and adenitis (pfapa) syndrome |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2020-07-01 |
description |
Periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) syndrome is the most common autoinflammatory disease in children and is often grouped together with hereditary periodic fever syndromes, although its cause and hereditary nature remain unexplained. We investigated whether differential DNA methylation was present in DNA from peripheral blood mononuclear cells (PBMC) in patients with PFAPA vs. healthy controls. A whole-epigenome analysis (MeDIP and MBD) was performed using pooled DNA libraries enriched for methylated genomic regions and identified candidate genes, two of which were further evaluated with methylation-specific restriction enzymes coupled with qPCR (MSRE-qPCR). The analysis showed that the PIK3AP1 and SPON2 gene regions are differentially methylated in patients with PFAPA. MSRE-qPCR proved to be a quick, reliable, and cost-effective method of confirming results from MeDIP and MBD. Our findings indicate that a B-cell adapter protein (PIK3AP1), as the PI3K binding inhibitor of inflammation, and spondin-2 (SPON2), as a pattern recognition molecule and integrin ligand, could play a role in the etiology of PFAPA. Their role and the impact of changed DNA methylation in PFAPA etiology and autoinflammation need further investigation. |
topic |
PFAPA differential methylation PIK3AP1 SPON2 MSRE-qPCR MeDIP |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2020.01322/full |
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