Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa

$\bf Background$ In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin. $\bf Objectives$ To analyse the mRNA and protein expression of NCSTN, Notch1–3, PIK3R3 and AKT3 in HS. $\bf Methods$ Skin samples from healthy controls, lesional and perilesional skin of HS patients with and without a positive family history were analysed by quantitative real-time RT-PCR and immunohistochemistry. Univariate statistical analyses were conducted regarding association between expression levels and patient's characteristics. $\bf Results$ Expression levels of all investigated genes showed significantly higher levels in lesional HS skin compared with healthy controls. Univariate analysis showed no association between a positive family history and mRNA expression levels. Perilesional HS skin of patients with mild disease severity (Hurley I) showed significant higher mRNA expression levels of the investigated pathway components compared to moderate (Hurley II) and severe disease (Hurley III). $\bf Conclusion$ We found no evidence for diminished expression levels of the Notch signalling. In contrast, the NCSTN, Notch and PI3K/AKT signalling components are overexpressed in HS. Future research is needed to investigate a possible pathogenetic role or to reveal a coactivation of these overexpressed components during inflammatory response in HS

Altered global 5-hydroxymethylation status in hidradenitis suppurativa

$\it Background:$ The pathogenesis of hidradenitis suppurativa (HS), with its complex inflammatory network, is still elusive. Imbalances in DNA methylation can lead to genome destabilization and have been assumed to play a role in inflammatory diseases. Global DNA methylation and hydroxymethylation have not been studied in HS yet. $\it Objective:$ We conducted this study to investigate the global DNA methylation and hydroxymethylation status in lesional and perilesional HS skin compared to healthy controls. $\it Methods:$ Immunohistochemical analysis was performed for 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in 30 lesional and 30 corresponding healthy-appearing perilesional HS tissue samples. We included 30 healthy subjects as an interindividual control group. $\it Results:$ 5-hmC levels were significantly lower in healthy-appearing perilesional ($\it {p}$ < 0.0001) and lesional HS skin ($\it {p}$ < 0.0001) when compared to healthy controls. There was no significant difference between lesional HS skin and perilesional HS skin regarding 5-hmC levels ($\it {p}$ = 0.6654). In contrast to 5-hmC, 5-mC staining showed no significant changes between the 3 groups. Univariate analysis revealed no significant association between patients’ characteristics, disease severity, and the levels of 5-mC and 5-hmC. $\it Conclusion:$ Our findings indicate that imbalances in DNA hydroxymethylation may play a role in the pathogenesis of HS rather than DNA methylation. Further studies are warranted to investigate the significance of DNA hydroxymethylation and the regulating enzymes in HS in order to advance our knowledge of the inflammatory network in this disease