An IL-17–dominant immune profile is shared across the major orphan forms of ichthyosis

Paller, Amy S.; Renert‐Yuval, Yael; Suprun, Maria; Esaki, Hideo; Oliva, Margeaux; Huynh, Thy; Ungar, Benjamin; Kunjravia, Norma; Friedland, Rivka; Peng, Xiangyu; Zheng, Xiuzhong; Estrada, Yeriel; Krueger, James G.; Choate, Keith; Suárez‐Fariñas, Mayte; Guttman‐Yassky, Emma

doi:10.1016/j.jaci.2016.07.019

Cited by 148 publications

(221 citation statements)

References 125 publications

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“…It is well established that the Th17/IL‐23 pathway is induced in psoriasis and a previous study of ARCI patients with TGM1 mutations could link this pathway to ichthyosis severity and inflammation . Furthermore, an increased IL‐17/IL‐22 activation in peripheral blood in patients with lamellar ichthyosis was shown to correlate with clinical variables in a recent study .…”

Section: Discussionmentioning

confidence: 81%

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Zhang

Ericsson

Weström

et al. 2018

Experimental Dermatology

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Autosomal recessive congenital ichthyosis (ARCI) is a group of monogenic skin disorders caused by mutations in any of at least 12 different genes, many of which are involved in the epidermal synthesis of ω‐O‐acylceramides (acylCer). AcylCer are essential precursors of the corneocyte lipid envelope crosslinked by transglutaminase‐1 (TGm‐1), or a yet unidentified enzyme, for normal skin barrier formation. We hypothesized that inactivating TGM1 mutations will lead to a compensatory overexpression of the transcripts involved in skin barrier repair, including many other ARCI‐causing genes. Using microarray, we examined the global mRNA expression profile in skin biopsies from five ARCI patients with TGM1 mutations and four healthy controls. There were a total of 599 significantly differentially expressed genes (adjusted P < 0.05), out of which 272 showed more than 1.5 log2fold‐change (FC) up‐ or down‐regulation. Functional classification of the latter group of transcripts showed enrichment of mRNA encoding proteins mainly associated with biological pathways involved in keratinocyte differentiation and immune response. Moreover, the expression of seven out of twelve ARCI‐causing genes was significantly increased (FC = 0.98‐2.05). Also, many of the genes involved in keratinocyte differentiation (cornified envelope formation) and immune response (antimicrobial peptides and proinflammatory cytokines) were upregulated. The results from the microarray analysis were also verified for selected genes at the mRNA level by qPCR and at the protein level by semi‐quantitative immunofluorescence. The upregulation of these genes might reflect a compensatory induction of acylCer biosynthesis as a part of a global barrier repair response in the patient′s epidermis.

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Section: Discussionmentioning

confidence: 81%

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Zhang

Ericsson

Weström

et al. 2018

Experimental Dermatology

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“…Nonetheless, little is currently known about the severity of itch in ichthyosis. The exact pathophysiology of itch in ichthyosis remains to be elucidated, but it may be related to skin inflammation …”

Section: Discussionmentioning

confidence: 99%

Burden of itch in ichthyosis: a multicentre study in 94 patients

Palma

Mazereeuw‐Hautier

Giehl

et al. 2019

Acad Dermatol Venereol

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Background From clinical experience, we know that itch is a major concern for many ichthyosis patients. Nonetheless, no previous studies specifically addressed the issue of itch in ichthyosis. Objective The objective of this study was to specifically address the burden of itch and all its dimensions in ichthyosis patients. Methods Ninety‐four ichthyosis patients from four different centres were recruited to participate in this cross‐sectional, questionnaire‐based study. All participants completed the Leuven Itch Scale, a multidimensional self‐report instrument that quantifies the frequency, duration, severity, distress, consequences and surface area of itch. Results Participants included 18 keratinopathic types, 55 autosomal recessive congenital ichthyoses, 11 X‐linked recessive ichthyoses (XLRIs), 6 Netherton's ichthyoses, 1 Sjögren–Larsson type, 1 Iocrin ichthyosis and 2 unknown subtypes. Itch occurred in 93% of all patients. In patients with itch, 63% reported that it was often or always present, although most itch episodes were short in duration. Itch, in all its dimensions, was worst in patients with Netherton syndrome. Patients with XLRI had in general a lower itch profile. About half of all ichthyosis patients reported to experience flares during a change in weather, in a hot environment or in stressful situations, whereas a cold environment led to itch in only 26% of patients. The most significant consequences of itching were lesions from scratching, difficulties in falling asleep, bad mood and loss of concentration. Conclusions Itch is a major concern in patients with ichthyosis, with significant impact on daily life. Research on future treatments should therefore take itch into consideration and itch should be evaluated in clinical studies. Among the studied subgroups, Netherton patients experienced the most severe consequences.

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“…A large German study showed no evidence for shared genetic risk variants of AD and CVD . Increased expression of IL‐17 has been shown in predominately Asian subtypes of AD and in ichthyoses, which, at least in theory, could increase the risk of CVD in Asian patients who might be affected by a more psoriatic form of AD …”

Section: Discussionmentioning

confidence: 99%

The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis

et al. 2018

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An IL-17–dominant immune profile is shared across the major orphan forms of ichthyosis

Abstract: Our data associate a shared T17/IL-23 immune fingerprint with the major orphan forms of ichthyosis and raise the possibility of IL-17-targeting strategies.

Cited by 148 publications

References 125 publications

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Patients with congenital ichthyosis and TGM1 mutations overexpress other ARCI genes in the skin: Part of a barrier repair response?

Burden of itch in ichthyosis: a multicentre study in 94 patients

The association with cardiovascular disease and type 2 diabetes in adults with atopic dermatitis: a systematic review and meta-analysis

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