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Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments
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Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 2985

Editor

Dr. Anna Michalak-Stoma

E-Mail Website
Guest Editor
Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
Interests: psoriasis; melanoma; immunology; dermoscopy

Special Issue Information

Dear Colleagues,

Psoriasis is regarded as both an autoimmune and autoinflammatory disease with genetic abnormalities modulated by environmental factors. Studies have revealed that psoriasis is associated with numerous comorbidities, including psoriatic arthritis, diabetes, hypertension, lipid disorders, obesity, cardiovascular diseases (CVDs), Crohn’s disease, non-alcoholic fatty liver disease, T-cell lymphoma, and depression. Our knowledge of the IL-23/Th17/IL-17 axis has contributed to the understanding of the pathogenesis of psoriasis. Many gene loci responsible for psoriasis susceptibility have also been identified. Some of them, such as PSORS2, PSORS3 and PSORS4, are associated with a genetic predisposition to metabolic syndrome, type 2 diabetes, familial hyperlipidemia and CVDs. 

Recent studies emphasize the influence of epigenetic factors on psoriasis. Understanding the signaling pathways in psoriasis has contributed to significant progress in its treatment. In the era of personalized medicine, it is important to understand the immunological, genetic and epigenetic biomarkers that affect the course of the disease, the risk of systemic disorders and allow for a better selection of effective therapy.

Dr. Anna Michalak-Stoma
Guest Editor

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Keywords

  • psoriasis
  • autoimmune disease
  • autoinflammatory disease
  • psoriatic arthritis
  • diabetes
  • hypertension
  • lipid disorders
  • obesity
  • cardiovascular diseases (CVDs)
  • immunological biomarkers
  • genetic biomarkers
  • epigenetic biomarkers

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Published Papers (4 papers)

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Research

26 pages, 480 KB  
Article
A Systemic Immune State Axis Distinguishes Psoriatic Arthritis from Psoriasis
by Yoon Kyeong Lee and Hyun-A. Seong
Int. J. Mol. Sci. 2026, 27(11), 5121; https://doi.org/10.3390/ijms27115121 - 5 Jun 2026
Viewed by 314
Abstract
Psoriasis and psoriatic arthritis (PsA) are systemic immune-mediated diseases, but the features that distinguish cutaneous-dominant psoriasis from musculoskeletal involvement remain unclear. We analyzed four core public cross-sectional datasets spanning whole-blood methylation, PBMC single-cell RNA sequencing summarized at the subject level, skin RNA sequencing, [...] Read more.
Psoriasis and psoriatic arthritis (PsA) are systemic immune-mediated diseases, but the features that distinguish cutaneous-dominant psoriasis from musculoskeletal involvement remain unclear. We analyzed four core public cross-sectional datasets spanning whole-blood methylation, PBMC single-cell RNA sequencing summarized at the subject level, skin RNA sequencing, and purified CD4+ T-cell methylation, and used two additional public skin cohorts for external contextual checks to define a disease inflammatory response axis (DIR) and a contrast-resolved systemic state coordinate (CRS) representing systemic immune state variation associated with PsA. In whole-blood methylation, DIR primarily separated healthy controls from psoriasis, whereas CRS separated psoriasis from PsA with minimal correlation to DIR. In untreated-only PBMC single-cell reanalysis, CRS separated PsA from PsO; the source-defined PSX subgroup (joint pain without CASPAR-classified PsA) showed heterogeneous subject-level positioning, with above-band enrichment concentrated at the cell-type level. Cell-type-resolved analyses localized CRS-related shifts to T-cell, monocyte, B-cell, and regulatory compartments and identified multicompartment pathway state remodeling along the CRS continuum. In contrast, skin RNA sequencing mainly captured lesional inflammatory burden and showed only limited additional PsA-related separation within the same tissue state. These findings support a model in which PsA is distinguished from psoriasis by an additional systemic immune state axis rather than by skin inflammatory burden alone. Full article
(This article belongs to the Special Issue Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments)
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22 pages, 2977 KB  
Article
Genome-Wide Association Study of Psoriasis, Psoriatic Arthritis, Anti–TNF-α Response, and Polygenic Risk Score in a Russian Cohort
by Arfenya E. Karamova, Anastasiia A. Buianova, Anastasiia A. Vorontsova and Alexey A. Kubanov
Int. J. Mol. Sci. 2026, 27(10), 4422; https://doi.org/10.3390/ijms27104422 - 15 May 2026
Viewed by 502
Abstract
Psoriasis is an immune-mediated inflammatory disease with a genetic component, characterized by dysregulation of cytokine signaling and activation of T lymphocytes. This study investigated genetic variants associated with psoriasis, psoriatic arthritis (PsA), and response to tumor necrosis factor alpha (TNF-α) inhibitors (adalimumab, infliximab, [...] Read more.
Psoriasis is an immune-mediated inflammatory disease with a genetic component, characterized by dysregulation of cytokine signaling and activation of T lymphocytes. This study investigated genetic variants associated with psoriasis, psoriatic arthritis (PsA), and response to tumor necrosis factor alpha (TNF-α) inhibitors (adalimumab, infliximab, and etanercept) in a Russian cohort. A genome-wide association study (GWAS) was conducted in 1026 psoriasis patients and 9212 controls using Infinium Global Screening Array-24 v3.0 microarrays. Exploratory analyses of treatment response (n = 48) and PsA (n = 96) were performed without covariate adjustment or explicit modeling of population structure. Polygenic risk scores (PRS) were derived from internally estimated effect sizes in a split-sample design. The GWAS replicated a robust association in the major histocompatibility complex (MHC) region (rs12189871 near HLA-C, p = 3.2 × 10−50, OR = 2.99 [2.59–3.45]). Additional loci included variants in ZC3H8 and PLCL2. Nominal signals were observed for IL18R1/IL18RAP in treatment response (including rs17027071) and for RCL1 and FBLIM1 in PsA; these findings remain exploratory. PRS demonstrated moderate predictive performance (AUC = 0.6355) and should be interpreted with caution given the study design. Overall, the results highlight a strong MHC signal in psoriasis, while findings for PsA and treatment response remain hypothesis-generating and require independent validation. Full article
(This article belongs to the Special Issue Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments)
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11 pages, 2339 KB  
Article
Aerobic Exercise Attenuates Epidermal Hyperplasia in an Obesity-Associated Psoriasiform Dermatitis Model
by Yoshihiro Matsuda, Shin Morizane, Daiki Takezaki, Yuma Sakamoto, Nobuyasu Baba, Masanori Iseki, Yoshio Kawakami, Tatsushi Shiomi and Tomoyuki Mukai
Int. J. Mol. Sci. 2026, 27(5), 2308; https://doi.org/10.3390/ijms27052308 - 28 Feb 2026
Viewed by 738
Abstract
Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice [...] Read more.
Obesity is an important risk factor for psoriasis, and clinical studies indicate that exercise interventions can improve disease severity. However, the mechanisms by which exercise influences psoriatic pathogenesis remain insufficiently understood. To investigate the effects of aerobic exercise on obesity-associated psoriasis, wild-type mice were fed a high-fat diet (HFD) for 7 weeks to induce obesity and subsequently underwent moderate-intensity treadmill running for 3 weeks. Psoriasiform dermatitis was induced by daily topical application of imiquimod (IMQ) to the skin for five consecutive days. HFD increased body weight, epididymal fat mass, and serum cholesterol. HFD-fed mice developed more severe IMQ-induced psoriatic skin changes compared with normal diet-fed mice. Treadmill exercise modestly reduced body weight gain and attenuated epidermal hyperplasia in HFD-fed mice. In contrast, inflammatory cytokine expression, including Tnfa, Il17a, and Il23a, showed modest increases in the skin of HFD-fed exercised mice, which did not parallel the improvement in epidermal hyperplasia. Overall, these findings indicate that while obesity exacerbates psoriasiform dermatitis, aerobic exercise ameliorates epidermal hyperplasia in obese mice without corresponding changes in inflammatory cytokine expression in the skin, suggesting that exercise may influence psoriatic skin changes through multiple metabolic and immunological pathways. Full article
(This article belongs to the Special Issue Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments)
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13 pages, 1347 KB  
Article
The Role of Elafin in the Pathogenesis of Psoriasis
by Mateusz Matwiejuk, Agnieszka Kulczyńska-Przybik, Bartłomiej Łukaszuk, Hanna Myśliwiec, Piotr Myśliwiec, Adrian Chabowski, Barbara Mroczko and Iwona Flisiak
Int. J. Mol. Sci. 2026, 27(4), 1767; https://doi.org/10.3390/ijms27041767 - 12 Feb 2026
Viewed by 752
Abstract
Psoriasis is a chronic, immune-mediated inflammatory disease that affects the skin, nails, joints, and cardiovascular system. In this study, involving 50 psoriatic patients and 28 healthy controls (patients with inguinal hernia), serum elafin levels were measured using enzyme-linked immunosorbent assay (ELISA). The results [...] Read more.
Psoriasis is a chronic, immune-mediated inflammatory disease that affects the skin, nails, joints, and cardiovascular system. In this study, involving 50 psoriatic patients and 28 healthy controls (patients with inguinal hernia), serum elafin levels were measured using enzyme-linked immunosorbent assay (ELISA). The results revealed significantly higher serum elafin levels in the psoriatic group compared to healthy individuals. Moreover, we observed a statistically significant positive correlation between serum elafin levels and the Psoriasis Area and Severity Index (PASI) scores. These findings indicate that elafin—a protein involved in psoriasis pathogenesis—is significantly altered in the serum of psoriatic patients and may be associated with disease severity. Full article
(This article belongs to the Special Issue Psoriasis and Associated Complications: Pathogenic Mechanisms, Gene Biomarkers and Treatments)
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