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Quantitative analysis of JAK/STAT signaling pathway in patients of inflammatory skin disorders

  • Observational Research
  • Published:
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Abstract

Background

Inflammatory skin diseases (ISDs), are characterized by dysregulated activation of innate and adaptive immune systems, with inflammatory cytokines playing a crucial role in their pathogenesis.

Objectives

This study aimed to investigate the involvement of Janus kinase/signal transduction and activator of transcription (JAK/STAT) signaling pathway in the pathogenesis of ISDs.

Methods

The study analyzed a total of 117 skin biopsies, comprising 31 from pyoderma gangrenosum (PG), 25 from hidradenitis suppurativa (HS), 35 from psoriasis patients, and 26 from control subjects. To assess the expression levels of JAK/STAT pathway components, immunohistochemical staining was performed on both the dermal and epidermal layers of the skin. The Histo score (H score) was utilized as the immunoexpression score to evaluate the staining intensity.

Results

The results indicated that all components of the JAK/STAT signaling pathway, except JAK2 and STAT6 in PG, JAK1, STAT4, and STAT6 in HS, and JAK1 in psoriasis, were overexpressed in the dermal skin compared to the control group (p < 0.05). Psoriatic skin had higher expression of STAT6 than both PG and HS and higher expression of JAK2 than PG (p < 0.05). Additionally, HS biopsies had higher expression of JAK2 and STAT6 compared to PG (p < 0.05). JAK1 expression was higher in PG than in HS, psoriasis, and the control group (mean H score was 265.8, 184.8, 191.4, and 113.1, p < 0.05, respectively).

Conclusions

This study provides new insights into the potential contribution of the JAK/STAT pathway to the pathogenesis of ISDs. The findings suggest that targeting this pathway could be a promising therapeutic strategy for treating these disorders.

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Funding

This research was supported by Pfizer (Grant number: ID#68022735).

Author information

Authors and Affiliations

  1. Department of Rheumatology, Faculty of Medicine, Dokuz Eylul University, Izmir, Turkey

    Tuba Demirci Yildirim, Aydan Köken Avşar, Fatos Onen & İsmail Sari

  2. Department of Pathology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey

    Aslı Kahraman

  3. Department of Rheumatology, Faculty of Medicine, Izmir Katip Celebi University, Izmir, Turkey

    Servet Akar

Authors
  1. Tuba Demirci Yildirim
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  2. Aslı Kahraman
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  3. Aydan Köken Avşar
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  4. Fatos Onen
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  6. İsmail Sari
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Contributions

TDY; conceptualization, visualization, formal analysis and writing—original draft. AK; performed pathological investigation. AKA, FO, and SA; conceptualization and helped in methodology. İS; conceptualization, visualization, formal analysis, and writing—original draft, and writing—review and editing. TDY, AK, and IS contributed to conceptualization of the study; TDY and AKA, data analysis and interpretation of the data; AK contributed pathological examination, TDY and İS contributed to statistical analysis; TDY, FO, SA and IS contributed to preparing and writing the manuscript. All authors reviewed, provided critical review at each stage, and approved the final version of the manuscript. İS is the guarantor.

Corresponding author

Correspondence to Tuba Demirci Yildirim.

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Conflicts of interest

The authors report no conflicts of interest.

Ethical approval

The study was conducted in accordance with the Helsinki Declaration and was approved by the local ethics committee (IRB number: 0166). Written informed consent was obtained from all participants. It was also registered on clinicaltrials.gov with the number NCT04792957.

Consent to publication

The authors declare that the submitted work is their own and that copyright has not been breached in seeking its publication. This study was presented as an oral presentation during the EULAR 2022 European Congress of Rheumatology, held from June 1–4, 2022, in Denmark.

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Demirci Yildirim, T., Kahraman, A., Köken Avşar, A. et al. Quantitative analysis of JAK/STAT signaling pathway in patients of inflammatory skin disorders. Rheumatol Int (2023). https://doi.org/10.1007/s00296-023-05418-y

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