DNA Methylation Profile in Psoriasis Vulgaris and Generalized Pustular Psoriasis Patients
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PROVIDER: PRJNA1303214 | ENA |
REPOSITORIES: ENA
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Project description:Epigenetics plays a role in the pathogenesis of psoriasis vulgaris and generalized pustular psoriasis (GPP) through DNA methylation modifications that cause changes in immune responses. Psoriasis vulgaris is dominated by autoimmune responses, driven by Th17 cells producing IL-17, whereas GPP is dominated by autoinflammatory responses resulting from IL-36 dysregulation and neutrophil hyperactivation. Objective: This study aims to determine the DNA methylation profile and analyze the differences in IL-17 and IL-36 levels in both psoriasis phenotypes and healthy controls. Method: This study employed a cross-sectional design, comprising 20 patients with psoriasis vulgaris, three patients with GPP, and 13 healthy controls. DNA methylation profiles were assessed using Reduced Representation Methylation Sequencing, while IL-17 and IL-36 levels were assessed using ELISA. Results: Increased 5-methyl cytosine (5mC) was identified in psoriasis vulgaris and GPP compared to healthy controls. Increased 5mC at the FOXP3 promoter was identified in GPP and psoriasis vulgaris with high IL-17 levels, while decreased 5mC at the CARD14 promoter was identified in psoriasis vulgaris with high IL-17 levels. GPP showed higher IL-17 levels than healthy controls (p<0.05). IL-17 levels in psoriasis vulgaris showed no significant difference compared to GPP and healthy controls (p>0.05). IL-36 levels did not differ significantly among the three groups, with the highest IL-36 levels observed in psoriasis vulgaris (p>0.05). Conclusion: Increased DNA methylation in the FOXP3 gene promoter is predicted to cause high IL- 17 levels in psoriasis vulgaris and GPP, while IL-36 levels are higher only in psoriasis vulgaris.
2025-08-07 | GSE304903 | GEO
Project description:Loss-of-function mutations in the IL36RN gene encoding IL-36 receptor antagonist (IL-36RA) cause familial generalized pustular psoriasis (GPP), which sometimes begins shortly after birth and is difficult to treat, and its effects on the epidermis are unclear. This study aimed to investigate the involvement of IL-36 receptor agonists in the epidermal formation of GPP. In this study, we found that IL-36 receptor agonists, especially mature IL-36γ, stimulate IL-8 and proIL-36γ production in the epidermis, while down-regulating the genes encoding epidermal cornified envelope-related proteins such as corneodesmosin. IL-36 receptor antagonists and monoclonal anti-IL-36γ antibodies counteract the effect of mature IL-36γ on corneodesmosin in keratinocytes in a dose-dependent manner. In the epidermis of generalized pustular psoriasis patients with IL36RN loss-of-function mutations, proIL-36γ is overproduced in the epidermis and corneodesmosin protein expression is markedly decreased in the region of giant subcorneal pustules called Kogoj’s spongiform pustules with high neutrophil infiltration. IL-8 induced by mature IL-36γ induces several neutrophils in the epidermis, and the newly produced proIL-36γ is cleaved to the mature form by neutrophil proteases. This newly produced mature IL-36γ was predicted to further suppress the gene expression of the granulosa-stratum-associated protein, corneodesmosin, leading to significant stratum corneum exfoliation and formation of giant subcorneal pustules. Overall, our results elucidate the mechanism underlying the formation of Kogoj’s spongiform pustules in generalized pustular psoriasis.
2023-11-09 | GSE235635 | GEO
Project description:Background. Generalized pustular psoriasis (GPP), palmoplantar pustular psoriasis (PPP) and Acrodermatitis continua suppurativa Hallopeau (ACH) are 3 prototypes of pustular psoriasis. Treating them with the established psoriasis armamentarium of immunomodulating therapies is more or less a trial-and-error game because pathophysiology has not been uncovered in detail yet. Objectives. To promote the decoding of immunological pathways in GPP as the maximal variant of pustular psoriasis. Methods. Focusing on transcriptomic differences in GPP versus PPP, bulk RNA sequencing of affected skin and healthy skin of 3 GPP and 3 PPP patients was performed, and results were compared to each other and to matching healthy skin samples. Results. Analysis of heatmaps confirmed the expected up-regulation of Interleukin (IL-) 17, IL-23 and IL-36 pathways, especially in GPP. Interestingly, in our GPP patients we detected an unexpected marked atopic-like milieu with an upregulated T-helper cell (Th) type 2 profile. This raises the bar concerning personalized medicine as recently introduced IL-36 blockage will probably not be able to succeed as a monotherapy in GPP. In PPP-patients the ‚typical‘ immune signatures, although differentially regulated, struck with a notable heterogeneity. The atopic markers were not as overregulated as in GPP. Further findings might elucidate clinical features of GPP: Severity of symptoms was accompanied by up-regulated SERPIN B4 and L-selectin. And, an overexpression of KYNU and TDO2 as a sign for imbalance in tryptophan metabolism could deliver an explanation for psychological findings like anxiety and depression during an acute flare of GPP. Conclusions. GPP has an atopic component next to notorious drivers of classical psoriasis and IL-36. Key factors for aggressiveness of disease and psychological distress during flares could be overexpression of SERPIN B4/L-selectin respectively KYNU/TDO2. Trials with a greater number of patients and even more meticulous transcriptome analysis possibly supported by artificial intelligence should be considered.
2025-05-01 | GSE293996 | GEO
Project description:Comparison of the Inflammatory Circuits in Psoriasis Vulgaris, Non-Pustular Palmoplantar Psoriasis, and Palmo-Plantar Pustular Psoriasis
| PRJNA839789 | ENA
Project description:There is a controversy surrounding the existence of palmoplantar pustulosis (PPP) and palmoplantar pustular psoriasis (PPPP) as separate clinical entities or as variants of the same clinical entity. We used gene expression microarray to compare gene expression in PPP and PPPP. PPP and PPPP could not be differentiated using gene expression microarray suggesting that they are not distinct clinical entities. Increased expression of GPRIN1, and ADAM23 in keratinocytes suggests that these proteins could be new therapeutic targets for PPP/PPPP. Skin biopsies from subjects with PPP (3), PPPP (6), psoriasis vulgaris (10) and acral skin from normal subjects (7) were analyzed using gene expression microarray. Principal component analysis showed that PPP and PPPP were different from psoriasis vulgaris and normal acral skin. However gene expression of PPP and PPPP clustered together and could not be used to differentiate PPP from PPPP. Gene-wise comparison between PPP and PPPP found no gene to be differentially expressed with a false discovery rate lower than 0.6. Surprisingly we found a higher expression of several genes involved in neural pathways (e.g. GPRIN and ADAM23) in PPP/PPPP as compared to psoriasis vulgaris and normal acral skin. Immunohistochemistry confirmed those findings and showed a keratinocyte localization for those proteins.
2016-06-30 | E-GEOD-80047 | biostudies-arrayexpress
Project description:Generalized pustular psoriasis (GPP) is a severe disease featured by neutrophilic pustules and enhanced IL-36 inflammatory pathway in skin. Recently, a transcriptomic analysis of PBMCs and neutrophils in MPO-deficient GPP patients has been performed in stable disease state. However, transcriptomic profiling of PBMCs during acute flare of GPP is unclear. Here, we reported a predominant neutrophil signature in GPP PBMC and a marked increase in the CD66+CD16+ low-density neutrophils (LDNs) within the PBMC fraction of acute GPP patients. Transcriptomic and functional analysis of LDNs revealed a hypoinflammatory phenotype yet enhanced release of neutrophil granule proteases, implicating that LDNs might contribute to the IL-36-mediated inflammation in GPP patients.
2022-04-18 | GSE200836 | GEO
Project description:Generalized pustular psoriasis (GPP) is a severe disease featured by neutrophilic pustules and enhanced IL-36 inflammatory pathway in skin. Recently, a transcriptomic analysis of PBMCs and neutrophils in MPO-deficient GPP patients has been performed in stable disease state. However, transcriptomic profiling of PBMCs during acute flare of GPP is unclear. Here, we reported a predominant neutrophil signature in GPP PBMC and a marked increase in the CD66+CD16+ low-density neutrophils (LDNs) within the PBMC fraction of acute GPP patients. Transcriptomic and functional analysis of LDNs revealed a hypoinflammatory phenotype yet enhanced release of neutrophil granule proteases, implicating that LDNs might contribute to the IL-36-mediated inflammation in GPP patients.
2022-04-20 | GSE200977 | GEO
Project description:The aim of our study was to explore lncRNA expression profile in keratinocytes of patients with psoriasis vulgaris to provide new insights into psoriasis.
2023-02-28 | GSE146149 | GEO
Project description:Transcriptomic analysis of low-density neutrophils (LDNs) in acute generalized pustular psoriasis (GPP)
| PRJNA826891 | ENA
Project description:A distinct immature low-density neutrophil population characterizes acute generalized pustular psoriasis [PBMC]
| PRJNA827794 | ENA