Pruritogenic molecules in the skin of patients with dermatomyositis

Anett Vincze; Erika Herczeg-Lisztes; Katalin Szabó; Tibor Gábor Béldi; Melinda Nagy-Vincze; Ágnes Pór; József Varga; Katalin Dankó; Tamás Biró; Balázs István Tóth; Zoltán Griger

doi:10.3389/fmed.2023.1168359

Pruritogenic molecules in the skin of patients with dermatomyositis

Front Med (Lausanne). 2023 May 11:10:1168359. doi: 10.3389/fmed.2023.1168359. eCollection 2023.

Affiliations

¹ Division of Clinical Immunology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
² Laboratory for Cellular and Molecular Physiology, Department of Physiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
³ Department of Pathology, Gyula Kenézy University Hospital, University of Debrecen, Debrecen, Hungary.
⁴ Division of Nuclear Medicine, Department of Medical Imaging, University of Debrecen, Debrecen, Hungary.
⁵ Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.

Abstract

Introduction: Pruritus is a common excruciating symptom in systemic autoimmune diseases such as dermatomyositis (DM) but the pathogenesis is not fully understood. We intended to investigate the targeted expression analysis of candidate molecules involved in the development of pruritus in lesional vs. non-lesional skin samples of patients affected with active DM. We looked for correlations between the investigated pruriceptive signaling molecules, disease activity, and itching sensation of DM patients.

Methods: Interleukins (IL-33 and IL-6), tumor necrosis factor α (TNF-α), peroxisome proliferator-activated receptor γ (PPAR-γ), and ion channels belonging to the transient receptor potential (TRP) family were analyzed. The expression of TNF-α, PPAR-γ, IL-33, IL-6, and TRP channels in lesional DM skin was evaluated by RT-qPCR and immunohistochemistry and was compared with non-lesional DM skin samples. Pruritus, disease activity, and damage of DM were evaluated by the 5-D itch scale and Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI), respectively. Statistical analysis was performed with IBM SPSS 28 software.

Results: A total of 17 active DM patients participated in the study. We could show that the itching score was positively correlated with the CDASI activity score (Kendall's tau-b = 0.571; p = 0.003). TNF-α gene expression was significantly higher in lesional DM skin than in non-lesional DM skin (p = 0.009) and differed in the subgroups of patients with different itch intensities (p = 0.038). The mRNA expression of lesional IL-6 correlated positively with 5-D itch and CDASI activity score (Kendall's tau-b = 0.585; p = 0.008 and 0.45; p = 0.013, respectively). TRPV4 expressions were positively correlated with CDASI damage score (Kendall's tau-b = 0.626; p < 0.001), but the mRNA expressions of the TRP family, PPAR-γ, IL-6, and IL-33 were not different in lesional and non-lesional samples. Immunohistochemistry analysis did not find significant alterations in the expressions of TNF-α, PPAR-γ, IL-6, and IL-33 in lesional and non-lesional regions.

Discussion: Our results argue that cutaneous disease activity, TNF-α, and IL-6 might play a central role in DM-associated itch, while TRPV4 plays a central role in tissue regeneration.

Keywords: IL-6; TNF-α; TRP channels; dermatomyositis; inflammatory myopathies; itch; pruritus.

Grants and funding

The presented study was supported by the Hungarian research grants of the National Research, Development, and Innovation Office and by the Hungarian research grant from the University of Debrecen (NRDIO 134791, 120187, EFOP-3.6.3-VEKOP-16-2017-00009). The study of BT was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.