Dataset Information

Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2.

ABSTRACT:

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-1β, thus sustaining a chronic inflammatory state, potentially leading to the onset of autoinflammatory skin diseases. Given the implication of the IL-1β 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 ~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.

SUBMITTER: Moltrasio C

PROVIDER: S-EPMC9862365 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Publications

Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2.

Moltrasio Chiara C Cagliani Rachele R Sironi Manuela M Clerici Mario M Pontremoli Chiara C Maronese Carlo Alberto CA Tricarico Paola Maura PM Crovella Sergio S Marzano Angelo Valerio AV

Vaccines 20230111 1

<h4>Background</h4>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-1β, thus sustaining a chronic inflammatory state, potentially leading to the onset of autoinflammatory skin diseases. Given the implication of the IL-1β pathway in the pathogenesis of syndromic hidradenitis suppurativa (HS), an autoinflammatory immune-m ...[more]

PMID: 36680007

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Project description:Hidradenitis suppurativa (HS) leads to disfigurement and painful eruptions in terminal hair follicles of the intertriginous skin, mainly of axillary, genitofemoral, and perianal sites. It is associated with an excessive impairment of quality of life, psychiatric disorders, and sexual distress. Body image impairment has been linked to depression and anxiety and has been described for some dermatologic disorders but has not yet been investigated in patients with HS.To investigate whether body image is diminished in patients with HS and whether disease severity, age at onset, disease duration, obesity, depression, and anxiety are linked to body image impairment.This 12-month (August 1, 2009, to August 31, 2010) case-control study with a prospective, observational, cross-sectional design recruited 47 consecutive patients with HS entering a tertiary care center and 45 healthy control individuals matched for age, sex, and body mass index (BMI). One patient and 4 controls failed to complete the questionnaire and were excluded from the evaluation. Data analysis was performed from December 1, 2013, to February 15, 2014.The Frankfurt Body Concept Scale (FKKS) and the Hospital Anxiety and Depression Scale (HADS) were given to patients and controls. Correlations among FKKS, HADS, and disease features were calculated.Of the 46 patients and 41 controls included in the evaluation (mean [SD] age, 35.6 [1.6] years; 40 [46%] male and 47 [54%] female), HS significantly reduced body image (mean FKKS score, 234.2 [5.4] in patients and 276.9 [5.7] in controls; P < .001), even when controlled for BMI. A correlation was found for the extent of body image disruption and BMI (r = -0.589; P < .001), HADS-depression score (r = -0.619; P < .001), and HADS-anxiety score (r = -0.340; P = .03). No association was found for the body image score and the severity of HS, age at onset of disease, and duration of disease. The body contact subscale score was the only subscale score that was not different between patients with HS and controls.Patients with HS have major body image impairment, which might lead to depression and anxiety, disorders that have been largely acknowledged in HS. This study identified another element of the psychosocial burden of patients with HS and reveals that body image could potentially be used as an outcome measure in future studies of HS.

Project description:Abstract Hidradenitis Suppurativa (HS) is an autoinflammatory skin disease more common in women and associated with hyper-androgenic disorders such as polycystic ovary syndrome. HS is characterized by chronic recurrent deep-seated painful nodules and draining tunnels in skin areas that follow the distribution of pubertal terminal hair growth. In women, HS disease activity varies with hormonal fluctuation across the menstrual cycle and pregnancy. Anti-androgens have shown promise in treatment of HS, but the pathophysiologic link between sex hormones and HS is unclear. We sought to further elucidate the role of sex hormones in the pathogenesis of HS. Objective: To determine if there is differential estrogen and androgen regulated gene expression in lesional compared to non-lesional skin transcriptome in HS patients. Methods: (a) We analyzed mRNA microarray data from lesional and non-lesional HS skin (GEO, GSE72702) (Blok JL, Br J Dermatol. 2016;174(6):1392). Inflammatory lesional skin from affected axilla or groin and non-lesional skin from the upper arm or leg was obtained from 17 patients with moderate to severe HS. We then examined differential expression of hormone regulated genes identified in existing androgen and estrogen gene expression signatures from prostate cancer cells [(VCaP treated with dihydrotestosterone (DHT)] and breast cancer cells [MCF7 treated with 17 beta-estradiol, (E2)] in the lesional and non-lesional skin transcriptomes of the HS patients. We identified overlap between the sets of genes that were either both upregulated or both repressed in HS lesions and the hormone-responsive prostate and breast cancer cell line models. Significance of differential gene expression was defined as FDR-adjusted p-value for two-tailed Student t-test less than 0.05. (b) After overlapping genes were identified, we used GeneGo Metacore pathway analysis software to explore the functional significance of the identified genes. Results: (a) Of the 3379 E2-upregulated probe sets in MCF7 breast cancer cells, 647 were significantly upregulated and 584 of 2871 E2-downregulated probe sets were significantly downregulated in HS lesions. Of the 1328 DHT-upregulated probe sets in prostate cancer cells, 341 were significantly upregulated and 196 of the 1251 DHT-downregulated probe sets were significantly downregulated in HS lesions. (b) Initial pathway analysis indicates that DHT upregulated genes in HS lesions are strongly enriched in innate immunity pathways, specifically, type 1 interferon signaling and class I MHC antigen presentation. Conclusion: There is substantial overlap between the transcriptional programme of sex steroids and transcriptional changes observed in HS lesional skin. In particular, androgen target genes are significantly enriched in innate immunity pathways, suggesting a functional link between the androgen signaling and the inflammatory process in HS lesions.

Dataset Information

Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2.

Background

Methods

Results

Conclusion

Publications

Autoinflammation in Syndromic Hidradenitis Suppurativa: The Role of AIM2.

Similar Datasets

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