Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2

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 beta, thus sustaining a chronic inflammatory state, potentially leading to the onset of autoinflammatory skin diseases. Given the implication of the IL-1 beta 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'- and 3' UTR and a region upstream of the first exon of similar to 800 bp was performed in twelve syndromic HS patients. Results: Six out of twelve syndromic HS patients carried a heterozygous variant c.-208 A >= 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.

Automated summary

A variant in the AIM2 gene was found in syndromic HS patients, suggesting its involvement in the pathogenesis of the disease. This variant was less common in sporadic HS and PG. These findings suggest a potential role of this variant in susceptibility to develop syndromic HS.