Patients with congenital ichthyosis show differential activation of IL-23/Th17 pathway among various disease subtypes - A single-centre experience

Background Congenital ichthyosis is a rare genetic skin condition characterised by aberrant keratinisation. This study focused on assessing the differential expression of Th17-related cytokines in different subtypes of ichthyosis and its correlation with clinical features. Aim We aimed to compare the gene expression of Th17-related genes and serum levels of IL-17 and IL-23 cytokines of the ichthyosis subgroups in the Indian population. Methods We analysed blood and skin specimens from consecutively diagnosed patients with congenital ichthyosis along with age/sex-matched healthy controls using reverse transcription-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), as well as immunohistochemistry (IHC) for Th17/IL-23 pathway genes. Additionally, IFN-γ (Th1), IL-4 (Th2), and IL-17A (Th17)-dominant cell populations were measured using flow cytometry. Clinical severity was assessed using measures including the overall ichthyosis score (ICH score), which integrates erythema (E), scaling (S), and body surface area (BSA) scores. Results This study analysed interleukins in 48 congenital ichthyosis patients and 34 controls. We observed a significant upregulation of IL-17A and IL-23 in all patients, particularly autosomal recessive congenital ichthyosis (ARCI), X-linked recessive ichthyosis (XLRI), and Netherton syndrome (NS) subtypes. Similarly, serum levels of IL-17A were significantly augmented in all ichthyosis subtypes, with ARCI showing the highest increase. Whereas, an increase in IL-23 was only detected in ARCI. NS patients had significantly increased IL-22 levels. Limitations Our study included small sample size and lack of mRNA and cytokines expression in skin biopsy samples. Conclusion The study highlighted significant immunological alterations in interleukins associated with the Th17 pathway in different subtypes of congenital ichthyosis.