Transcriptomic Analysis of the Major Orphan Ichthyosis Subtypes Reveals Shared Immune and Barrier Signatures

T Helper 17/T Helper 22‒Skewed Inflammation with Epidermal Barrier Dysfunction in Nonmajor Inherited Ichthyosis Subtypes

“…Although robust activation of the Th17/Th22 pathway was shared by all of the four orphan-form ichthyoses examined, Kim et al (2022) also showed that other inflammatory pathways such as Th1 and Th2 showed somewhat different trends in each subtype, although these were generally modest. IL12RB2 was upregulated in NS, CIE, and EI, but other Th1-related genes such as IFNg, IL12B, and CXCL9/11 were upregulated in CIE alone.…”

“…Although several studies using RT-qPCR and microarray have previously suggested that the four orphan-form ichthyoses (i.e., LI, CIE, NS, and EI) shared T helper (Th) 17/Th22-type inflammation similar to psoriasis, these were not conclusive because of small sample sizes (Malik et al, 2019;Paller et al, 2017). In their article in the Journal of Investigative Dermatology, Kim et al (2022) performed skin transcriptomic analysis on more samples (Total: n ¼ 54, NS: n ¼ 7, LI: n ¼ 16, CIE: n ¼ 18, and EI: n ¼ 13), showing that the Th17/Th22 pathway was upregulated and that genes related to tight junctions were downregulated in these rare ichthyosis subtypes.…”

“…Using global transcriptomic analysis, Kim et al (2022) showed that the downregulation of several lipid metabolism markers was observed, except in the case of EI. These markers included genes related to the synthesis of intercorneocyte lipids such as sphingolipids and ceramides (e.g., ELOVL3 and FA2H), which could be involved in SC barrier dysfunction through impairment of moisture retention and increased transepidermal water loss.…”

“…Skin microarray data (n ¼ 21) also showed upregulation of IL-17, although statistical significance was not observed (Malik et al, 2019). Kim et al (2022) performed a comprehensive transcriptomic analysis on 54 patients with one of the four orphan-form ichthyoses (i.e., LI, CIE, NS, and EI) that showed a significant upregulation of various Th17-and Th22-related…”

Selected genodermatoses – Status quo and future prospects

“…While all subtypes exhibited a significant T helper (Th) 22/Th17-mediated immune response, additional changes were found in the Th2-mediated immune response especially in Netherton syndrome and a changed Th1 immune response in congenital ichthyosiform erythroderma. 34 Upregulation of interleukin (IL)-36α and IL-36γ had already been demonstrated in harlequin ichthyosis. 35 For this reason, several biologics primarily approved for psoriasis, psoriasis arthritis, and atopic eczema that exhibit inhibitory effects on specific cytokines have recently been used in various types of hereditary ichthyosis associated with moderate to severe inflammation of the skin.…”