Mutation analysis of <i><scp>IL</scp>36<scp>RN</scp></i> gene in Japanese patients with palmoplantar pustulosis

Takahashi, Tamiko; Fujimoto, Noriki; Kabuto, Miho; Nakanishi, Takeshi; Tanaka, Toshihiro

doi:10.1111/1346-8138.13551

Cited by 28 publications

(10 citation statements)

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“…In contrast, Mössner et al found four patients with heterozygous IL36RN variants who were without pathogenicity among 251 PPP patients, which suggested that PPP was not associated with loss-of-function IL36RN mutations in Europeans 8 . Takahashi et al found four of 88 Japanese PPP patients had heterozygous IL36RN variants, and similarly concluded that these variants did not seem to be associated with the phenotype of PPP 7 . The different results in these reports may reflect the different ethnicities of the study populations.…”

Section: Discussionmentioning

confidence: 97%

“…IL36RN may have no association with the clinical manifestation of PPP. Another piece of evidence is that the skin lesions of heterozygous IL36RN PPP patients stained positively for IL-36Ra in an immunohistochemical analysis, showing no difference with normal controls 7 . Moreover, Onoufriadis et al concluded that three GPP patients had homozygous (p.Ser113Leu) or compound heterozygous mutations (p.Ser113Leu, p.Arg48Trp), but no mutation was observed in another two GPP patients with PPP complications 14 .…”

Section: Discussionmentioning

confidence: 99%

“…The relationship between IL36RN and PPP has also been studied, but the results are controversial. Research in Japan and Europe has suggested that PPP has no association with IL36RN mutation 7, 8. However, another European study indicated that GPP and PPP underlie a spectrum of IL36RN variant-associated pustular psoriasis 9 .…”

Section: Introductionmentioning

confidence: 99%

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Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients

Shen

Jin

2019

Anais Brasileiros de Dermatologia

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BackgroundPalmoplantar pustulosis is considered to be a localized pustular psoriasis confined to the palms and soles. Mutation of the IL36RN gene, encoding interleukin-36 receptor antagonist (IL-36Ra), is associated with generalized pustular psoriasis, but IL36RN mutations in Chinese palmoplantar pustulosis patients have not previously been investigated.ObjectiveThe aim of this study was to evaluate the mutation of IL36RN in Chinese patients with palmoplantar pustulosis.MethodsFifty-one Han Chinese patients with palmoplantar pustulosis were recruited. All exons and exon-intron boundary sequences of IL36RN were amplified in polymerase chain reactions, and Sanger sequencing of the amplicons was performed.ResultsAmong the 51 palmoplantar pustulosis patients, four different single-base substitutions were identified in nine patients. The mutations were c.140A>G/p.Asn47Ser in five patients, c.258G>A/p.Met86IIe in two patients, and c.115+6T>C and c.169G>A/p.Val57IIe in one patient each. All mutations were heterozygous. Comparison with the human genome database and reported literature suggested that these variants may not be pathogenic mutations causing palmoplantar pustulosis. Furthermore, there was no difference in disease severity, onset age, or disease duration between patients with these heterozygous IL36RN variants and those without (p > 0.1).Study limitationLack of the further evaluation of IL36Ra protein in palmoplantar pustulosis lesions.ConclusionsThe four variants of IL36RN identified did not appear to be associated with the specific phenotypes of palmoplantar pustulosis.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

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Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients

Shen

Jin

2019

Anais Brasileiros de Dermatologia

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“…In a study on 57 Chinese patients with pustular psoriasis, IL36RN mutations were found in 75% of GPP patients and 94% of ACH patients [ 21 ]. On the contrary, Takahashi and colleagues performed mutation analysis of the IL36RN gene in 88 Japanese patients with PPP and identified three types of single base substitutions of IL36RN; they were heterozygous and different from those found in European studies, and they were considered to be of no pathogenic relevance [ 22 , 23 ]. Furthermore, other studies in patients with PPP have shown that the combined frequency of AP1S3 and IL36RN mutations accounts for less than 10% of patients, suggesting not only that PPP is not clearly associated with IL36RN but also that known genes account for only a minority of disease cases [ 17 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

Iznardo

Puig

2021

IJMS

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Unmet needs in the treatment of psoriasis call for novel therapeutic strategies. Pustular psoriasis and psoriatic arthritis often represent a therapeutic challenge. Focus on IL-36 cytokines offers an interesting approach, as the IL-36 axis has been appointed a critical driver of the autoinflammatory responses involved in pustular psoriasis. Two IL-36R blocking antibodies, imsidolimab and spesolimab, are currently undergoing phase II and III clinical trials, with promising results.

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“…Because the deficiency of IL-36R antagonist appears to be associated with various autoimmune diseases, 15 , 17 , 19 , 20 the underlying mechanism might be a dysfunction in controlling the basal activity of IL-36R signaling. This was supported by the finding that, unlike IL-1, IL-36 cytokines have basal expression in unchallenged tissues and cells.…”

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confidence: 99%

Role of IL-36γ/IL-36R Signaling in Corneal Innate Defense AgainstCandida albicansKeratitis

Dai

Gao

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Interleukin (IL)-36 cytokines have been shown to play either beneficial or detrimental roles in the infection of mucosal tissues in a pathogen-dependent manner, but their involvement in fungal keratitis remains elusive. We herein investigated their expression and function in mediating corneal innate immunity against Candida albicans infection. METHODS.Gene expression in mouse corneas with or without C. albicans infection was determined by regular RT-and real-time (q)-PCR, Western blot analysis, ELISA or proteome profile assay. The severity of C. albicans keratitis was assessed using clinical scoring, bacterial counting, and myeloperoxidase (MPO) activity as an indicator of neutrophil infiltration. IL36R knockout mice and IL-33-specific siRNA were used to assess the involvement IL-33 signaling in C. albicans-infected corneas. B6 CD11c-DTR mice and clodronate liposomes were used to define the involvement of dendritic cells (DCs) and macrophages in IL-36R signaling and C. albicans keratitis, respectively.RESULTS. IL-36γ were up-regulated in C57BL6 mouse corneas in response to C. albicans infection. IL-36 receptor-deficient mice display increased severity of keratitis, with a higher fungal load, MPO, and IL-1β levels, and lower soluble sIL-1Ra and calprotectin levels. Exogenous IL-36γ prevented fungal keratitis pathogenesis with lower fungal load and MPO activity, higher expression of sIL-1Ra and calprotectin, and lower expression of IL-1β, at mRNA or protein levels. Protein array analysis revealed that the expression of IL-33 and REG3G were related to IL-36/IL36R signaling, and siRNA downregulation of IL-33 increased the severity of C. albicans keratitis. Depletion of dendritic cells or macrophages resulted in severe C. albicans keratitis and yet exhibited minimal effects on exogenous IL-36γ -induced protection against C. albicans infection in B6 mouse corneas. CONCLUSIONS.IL-36/IL36R signaling plays a protective role in fungal keratitis by promoting AMP expression and by suppressing fungal infection-induced expression of proinflammatory cytokines in a dendritic cell-and macrophage-independent manner.

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Mutation analysis of IL36RN gene in Japanese patients with palmoplantar pustulosis

Cited by 28 publications

References 14 publications

Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients

Lack of association between mutation in IL36RN and palmoplantar pustular psoriasis in Chinese patients

Exploring the Role of IL-36 Cytokines as a New Target in Psoriatic Disease

Role of IL-36γ/IL-36R Signaling in Corneal Innate Defense AgainstCandida albicansKeratitis

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