{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:14:34Z","timestamp":1792790074228,"version":"4.5.0"},"reference-count":25,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T00:00:00Z","timestamp":1673395200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["SG-2019- 12369421"],"award-info":[{"award-number":["SG-2019- 12369421"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: AIM2 is a key cytoplasmatic pathogen-sensor that detects foreign DNA from viruses and bacteria; it can also recognize damaged or anomalous presence of DNA, promoting inflammasome assembly and activation with the secretion of IL-1\u03b2, thus sustaining a chronic inflammatory state, potentially leading to the onset of autoinflammatory skin diseases. Given the implication of the IL-1\u03b2 pathway in the pathogenesis of syndromic hidradenitis suppurativa (HS), an autoinflammatory immune-mediated skin condition, the potential involvement of AIM2 was investigated. Methods: Sequencing of the whole coding region of the AIM2 gene, comprising 5\u2032- and 3\u2032 UTR and a region upstream of the first exon of ~800 bp was performed in twelve syndromic HS patients. Results: Six out of twelve syndromic HS patients carried a heterozygous variant c.\u2212208 A \u2265 C (rs41264459), located on the promoter region of the AIM2 gene, with a minor allele frequency of 0.25, which is much higher than that reported in 1000 G and GnomAD (0.075 and 0.094, respectively). The same variant was found at a lower allelic frequency in sporadic HS and isolated pyoderma gangrenosum (PG) (0.125 and 0.065, respectively). Conclusion: Our data suggest that this variant might play a role in susceptibility to develop syndromic forms of HS but not to progress to sporadic HS and PG. Furthermore, epigenetic and\/or somatic variations could affect AIM2 expression leading to different, context-dependent responses.<\/jats:p>","DOI":"10.3390\/vaccines11010162","type":"journal-article","created":{"date-parts":[[2023,1,12]],"date-time":"2023-01-12T02:28:44Z","timestamp":1673490524000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0060-5870","authenticated-orcid":false,"given":"Chiara","family":"Moltrasio","sequence":"first","affiliation":[{"name":"Dermatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Medical Surgical and Health Sciences, University of Trieste, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2670-3532","authenticated-orcid":false,"given":"Rachele","family":"Cagliani","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2267-5266","authenticated-orcid":false,"given":"Manuela","family":"Sironi","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5920-6191","authenticated-orcid":false,"given":"Mario","family":"Clerici","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"},{"name":"Don C. Gnocchi Foundation ONLUS, IRCCS, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Pontremoli","sequence":"additional","affiliation":[{"name":"Scientific Institute IRCCS E. MEDEA, Bioinformatics, 23842 Bosisio Parini, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9449-849X","authenticated-orcid":false,"given":"Carlo Alberto","family":"Maronese","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1954-4126","authenticated-orcid":false,"given":"Paola Maura","family":"Tricarico","sequence":"additional","affiliation":[{"name":"Department of Advanced Diagnostics, Institute for Maternal and Child Health-IRCCS \u201cBurlo Garofolo\u201d, 34137 Trieste, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-1168","authenticated-orcid":false,"given":"Sergio","family":"Crovella","sequence":"additional","affiliation":[{"name":"Biological Science Program, Department of Biological and Environmental Sciences, College of Arts and Sciences, University of Qatar, Doha 2713, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8160-4169","authenticated-orcid":false,"given":"Angelo Valerio","family":"Marzano","sequence":"additional","affiliation":[{"name":"Dermatology Unit, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Pathophysiology and Transplantation, Universit\u00e0 degli Studi di Milano, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.3389\/fimmu.2018.02379","article-title":"Pattern Recognition Receptors and the Host Cell Death Molecular Machinery","volume":"9","author":"Adjemian","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/nature10759","article-title":"Inflammasomes in health and disease","volume":"481","author":"Strowig","year":"2012","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1038\/nature07725","article-title":"AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC","volume":"458","author":"Hornung","year":"2009","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1016\/j.bbrc.2004.12.056","article-title":"The HIN domain of IFI-200 proteins consists of two OB folds","volume":"327","author":"Albrecht","year":"2005","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"82ra38","DOI":"10.1126\/scitranslmed.3002001","article-title":"Cytosolic DNA triggers inflammasome activation in keratinocytes in psoriatic lesions","volume":"3","author":"Dombrowski","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1101\/gr.100289.109","article-title":"Changes in the pattern of DNA methylation associate with twin discordance in systemic lupus erythematosus","volume":"20","author":"Javierre","year":"2010","journal-title":"Genome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1111\/exd.12037","article-title":"Strong induction of AIM2 expression in human epidermis in acute and chronic inflammatory skin conditions","volume":"21","author":"Bergboer","year":"2012","journal-title":"Exp. Dermatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1056\/NEJMcp1014163","article-title":"Clinical practice. Hidradenitis suppurativa","volume":"366","author":"Jemec","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1111\/jdv.14464","article-title":"Recognizing syndromic hidradenitis suppurativa: A review of the literature","volume":"31","author":"Gasparic","year":"2017","journal-title":"J. Eur. Acad. Dermatol. Venereol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1588","DOI":"10.1111\/bjd.15226","article-title":"Autoinflammation in pyoderma gangrenosum and its syndromic form (pyoderma gangrenosum, acne and suppurative hidradenitis)","volume":"176","author":"Marzano","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.3899\/jrheum.171007","article-title":"Is SAPHO Syndrome Linked to PASH Syndrome and Hidradenitis Suppurativa by Nicastrin Mutation? A Case Report","volume":"45","author":"Li","year":"2018","journal-title":"J. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.jdermsci.2020.05.004","article-title":"Altered keratinization and vitamin D metabolism may be key pathogenetic pathways in syndromic hidradenitis suppurativa: A novel whole exome sequencing approach","volume":"99","author":"Brandao","year":"2020","journal-title":"J. Dermatol. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1159\/000521263","article-title":"Whole-Exome Sequencing in 10 Unrelated Patients with Syndromic Hidradenitis Suppurativa: A Preliminary Step for a Genotype-Phenotype Correlation","volume":"238","author":"Marzano","year":"2022","journal-title":"Dermatology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Moltrasio, C., Tricarico, P.M., Romagnuolo, M., Marzano, A.V., and Crovella, S. (2022). Hidradenitis Suppurativa: A Perspective on Genetic Factors Involved in the Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10082039"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1038\/s41572-020-0149-1","article-title":"Hidradenitis suppurativa","volume":"6","author":"Sabat","year":"2020","journal-title":"Nat. Rev. Dis. Primers."},{"key":"ref_17","unstructured":"(2022, October 10). Ensemble. Available online: https:\/\/www.ensembl.org\/."},{"key":"ref_18","unstructured":"(2022, October 10). GnomAD. Available online: https:\/\/gnomad.broadinstitute.org."},{"key":"ref_19","unstructured":"(2022, October 10). dbSNP, Available online: http:\/\/www.ncbi.nlm.nih.gov\/SNP."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1111\/imr.12618","article-title":"The AIM2 inflammasome: Sensor of pathogens and cellular perturbations","volume":"281","author":"Lugrin","year":"2018","journal-title":"Immunol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1007\/s12016-017-8621-8","article-title":"A Comprehensive Review of Neutrophilic Diseases","volume":"54","author":"Marzano","year":"2018","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e187","DOI":"10.1097\/MD.0000000000000187","article-title":"Association of pyoderma gangrenosum, acne, and suppurative hidradenitis (PASH) shares genetic and cytokine profiles with other autoinflammatory diseases","volume":"93","author":"Marzano","year":"2014","journal-title":"Medicine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"401","DOI":"10.3899\/jrheum.090456","article-title":"Genetic susceptibility factors in a cohort of 38 patients with SAPHO syndrome: A study of PSTPIP2, NOD2, and LPIN2 genes","volume":"37","author":"Chapeton","year":"2010","journal-title":"J. Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1111\/bjd.13493","article-title":"The genetics of pyoderma gangrenosum and implications for treatment: A systematic review","volume":"172","author":"DeFilippis","year":"2015","journal-title":"Br. J. Dermatol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"293417","DOI":"10.1155\/2015\/293417","article-title":"Clinical features and genetic background of the periodic Fever syndrome with aphthous stomatitis, pharyngitis, and adenitis: A single center longitudinal study of 81 patients","volume":"2015","author":"Perko","year":"2015","journal-title":"Mediat. Inflamm."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/1\/162\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:03:32Z","timestamp":1760119412000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/11\/1\/162"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,11]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,1]]}},"alternative-id":["vaccines11010162"],"URL":"https:\/\/doi.org\/10.3390\/vaccines11010162","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,11]]}}}