MicroRNA profile in patients with plaque psoriasis and palmoplantar pustular psoriasis

Evgeniya V. Turchik; Турчик Евгения Владимировна; Elena E. Timechko; Тимечко Елена Евгеньевна; Alexey M. Yakimov; Якимов Алексей Михайлович; Anastasia A. Vasilieva; Васильева Анастасия Александровна; Diana V. Dmitrenko; Дмитренко Диана Викторовна; Yuri Yu. Vinnik; Винник Юрий Юрьевич; Pavel A. Shesternya; Шестерня Павел Анатольевич

doi:10.25208/vdv16967

MicroRNA profile in patients with plaque psoriasis and palmoplantar pustular psoriasis

Authors: Turchik E.V.¹, Timechko E.E.¹, Yakimov A.M.¹, Vasilieva A.A.¹, Dmitrenko D.V.¹, Vinnik Y.Y.¹, Shesternya P.A.¹
Affiliations:
1. Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University
Issue: Vol 102, No 2 (2026)
Pages: 43-50
Section: ORIGINAL STUDIES
Submitted: 02.03.2026
Accepted: 13.05.2026
Published: 12.06.2026
URL: https://vestnikdv.ru/jour/article/view/16967
DOI: https://doi.org/10.25208/vdv16967
EDN: https://elibrary.ru/swtace
ID: 16967

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Abstract

Background: Palmoplantar pustular psoriasis (PPPP) is considered a clinically and pathogenetically distinct form of psoriasis; however, its molecular patterns remain insufficiently understood. The role of circulating small non-coding RNA molecules (microRNAs) in the development of phenotypic differences between plaque psoriasis and PPPP has not been fully elucidated.

Aim: To evaluate plasma microRNA expression patterns in patients with plaque psoriasis and PPPP and to identify differences between the clinical disease subtypes.

Methods: A comparative study including 38 patients with plaque psoriasis and 31 patients with PPPP was conducted. Plasma expression levels of hsa-miR-126-5p, hsa-miR-210-3p, hsa-miR-10b-5p, and hsa-miR-130a-3p were measured using quantitative real-time polymerase chain reaction with relative expression estimated using the 2^−ΔΔ^Ct method. Statistical processing was performed using parametric and non-parametric tests adjusted for multiple comparisons.

Results: Patients with PPPP have demonstrated a statistically significant increased expression of hsa-miR-126-5p (p = 0.04) and hsa-miR-210-3p (p = 0.01) compared with plaque psoriasis. The differences in hsa-miR-10b-5p and hsa-miR-130a-3p expression were not statistically significant. Stratification by the PASI score has shown that the expression profile in PPPP was comparable to that observed in more severe forms of plaque psoriasis.

Conclusion: The identified changes in microRNA expression indicate molecular differences between the clinical phenotypes of psoriasis. Thus, hsa-miR-126-5p and hsa-miR-210-3p may be considered as potential markers of molecular activity in PPPP and require further investigation.

Keywords

psoriasis, palmoplantar pustular psoriasis, plaque psoriasis, microRNA, plasma expression, molecular markers

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Background

MicroRNAs (small non-coding ribonucleic acid molecules) are the most abundant class of post-transcriptional regulators in the human genome. By binding to complementary sequences in target genes, microRNAs inhibit their translation into protein and suppress the expression of protein-coding genes. In psoriasis, microRNAs are known to regulate a wide range of pathological processes, including hyperproliferation, cytokine and chemokine production in keratinocytes, and T cell activation [1].

In this context, microRNAs are being actively investigated as potential biomarkers and therapeutic targets. Certain findings regarding this issue are summarized in a recently published review including 17 studies on the microRNA profile in patients with plaque psoriasis [2]. However, the polymorphism of the clinical pattern in psoriasis limits the interpretation of the findings and warrants further study of the disease.

The pathogenesis of pustular psoriasis is much closer to an autoinflammatory than to an autoimmune reaction, wherein the aberrant production of interleukins, IL-1 and IL- 36, driven by neutrophil proteases, leads to an uncontrolled surge in their biological activity and distinguishes them from the classic “tumor necrosis factor alpha–IL-17/IL-23” pattern of plaque psoriasis [3]. In this regard, of undoubted interest is the localized form of pustular psoriasis, palmoplantar pustular psoriasis (PPPP), which has an estimated frequency of 0.05 to 0.12 % [4, 5]. The unique signature of differential gene expression in patients with palmoplantar psoriasis confirms the underlying pathogenetic differences between PPPP and plaque psoriasis [6]. From a clinical perspective, managing patients with PPPP requires considering the spectrum of comorbidities, a significantly lower rate of psoriatic arthritis, and differences in therapeutic approaches [5, 7, 8].

Therefore, a comparative analysis of circulating microRNA expression in patients with various forms of psoriasis is relevant and of undoubted research interest. We have not found any published papers regarding microRNA expression patterns in patients with PPPP in the available literature.

Methods

The study was conducted in accordance with the Declaration of Helsinki [9].

Analysis of plasma microRNA expression

To analyze microRNA expression, whole blood from the cubital vein was collected in two vacuum tubes containing ethylenediaminetetraacetic acid and then centrifuged to separate the plasma fraction according to standard protocols [10]. The separated plasma was stored at −80°C until further testing.

The total RNA was isolated from blood plasma using a RIBO-sorb kit (K2-1-Et-100; Federal Budget Institution of Science “Central Research Institute of Epidemiology of Rospotrebnadzor”, Russia) according to the manufacturer’s protocol. Contaminated deoxyribonucleic acid (DNA) was removed using DNase I (3911.2000; diaGene, Russia). Quantification was performed using Qubit 4 (Thermo Fisher Scientific, USA) and Equalbit RNA HS Assay Kit (EQ211- 01; Vazyme, China).

The isolated RNA (1 µg) was reverse-transcribed using specific stem-loop primers and the HiScript II Reverse Transcriptase kit for the synthesis of complementary DNA (R211-01, Vazyme, China) according to the manufacturer’s protocol.

Real-time polymerase chain reaction (PCR) was performed on a LightCycler 480 Instrument II thermocycler (Roche, Switzerland) using BioMaster HS-Taq PCR (2×) reagents (MH010-200; Biolabmix, Russia), the intercalating dye SYBR Green I (PB025M; Eurogen, Russia), and synthesized forward and reverse primers. The primers were developed using the sRNAprimerDB software (http://www.srnaprimerdb.com) and subsequently analyzed for dimerization using the Multiple Primer Analyzer (Thermo Fisher Scientific, USA).

MicroRNAs for further analysis were selected by evaluating transcriptomic data on whole blood mRNA expression in patients with various forms of psoriasis. The four microRNAs selected for further analysis were hsa-miR-210-3p, hsa-miR-10b-5p, hsa-miR-130a-3p, and hsa-miR-126-5p.

MicroRNA expression was calculated using the Livak method [11]. Expressions exceeding 40 cycles during fluorescence detection were excluded from further analysis. Hsa-miR-16 was used as an endogenous microRNA control because it is stably detected in blood plasma [12].

Ethical expert evaluation

The study fully adhered to good clinical practice and was approved by the local ethics committees of Krasnoyarsk Regional Dermatovenerological Dispensary No. 1 (Protocol No. 1 dated 17.02.2022) and Krasnoyarsk State Medical University named after Professor V.F. Voino-Yasenetsky (Protocol No. 114/2022 dated 05.10.2022).

Statistical data processing

Statistical data processing was performed using the Python programming language v. 3.11.10 [13] in the Spyder 6 development environment [14], utilizing the pandas, scipy, and seaborn packages.

The distribution of quantitative data was analyzed using the Shapiro–Wilk statistical test. Data obeying a normal distribution were described using means and standard deviations, whereas non-normally distributed data were described using medians (Me) and the 25th and 75th percentiles [Q25; Q75]. Outliers were detected using the Grubbs’ test. Intergroup differences were identified using the following tests: Student’s t-test, Mann–Whitney test, and Welch test for normally distributed data. For non-normally distributed data and samples with different sizes and variances, all resulting p-values were adjusted using the Benjamini–Hochberg procedure for multiple comparisons.

Intergroup frequencies of the nominal data were compared using the χ² test. The quality of the binary classification was evaluated using Receiver Operating Characteristic (ROC) analysis.

Results

The study enrolled 38 patients with plaque psoriasis and 31 patients with PPPP. The severity and prevalence of psoriasis were evaluated based on the Psoriasis Area and Severity Index (PASI). The patient groups were comparable in key parameters, except for age. The cause is not only the relative rarity of PPPP, but also the later onset of this psoriasis form. The demographic and clinical characteristics of the patients are shown in Table 1.

Table 1. Clinical and demographic characteristics of patients

Таблица 1. Клиническо-демографическая характеристика пациентов

Characteristics	Plaque psoriasis	Palmoplantar pustular psoriasis	p
Age, years, Me [Q25; Q75]	35 [28; 40]	43 [34; 50]	0.004
Gender, %: male female	19 (50.0 ± 8.1) 19 (50.0 ± 8.1)	12 (38.7 ± 8.8) 19 (61.3 ± 8.8)	0.35
PASI, n (%): ≤10 >10	14 (36.8) 24 (63.2)	—	—
Disease duration, years, Me [Q25; Q75]	7 [5; 15]	7 [5; 9]	0.17
Smoking status (smoker/non-smoker), n (%)	4 (10.5)	6 (19.4)	0.89
Body mass index, Me [Q25; Q75]	24.91 [22.20; 29.50]	27.76 [24.50; 31.40]	0.15
Arterial hypertension, n (%)	7 (18.4)	10 (32.3)	0.78
Diabetes mellitus, n (%)	2 (5.3)	3 (9.7)	0.97

Analysis of blood plasma microRNA (hsa-miR-126-5p, hsa-miR-10b-5p, hsa-miR-130a-3p, and hsa-miR-210-3p) expression demonstrated the following patterns: a 33 % increase in hsa-miR-126-5p expression (p = 0.04, test power 0.96) and a 40 % increase in hsa-miR-210-3p expression (p = 0.01, test power 0.97) in patients with PPPP compared with plaque psoriasis. The fold change (FC) in expression of these microRNAs presented as a base-2 logarithm in Fig. 1.

Fig. 1. microRNA expression pattern: а — hsa-miR-126-5p; б — hsa-miR-210-3p. ПсО — plaque psoriasis; ЛППП — palmoplantar pustular psoriasis

Рис. 1. Паттерн экспрессии микроРНК: а — hsa-miR-126-5p; б — hsa-miR-210-3p. ПсО — бляшечный псориаз; ЛППП — ладонно-подошвенный пустулезный псориаз

The quality of binary classification based on selected microRNA expression was assessed by generating ROC curves (Fig. 2).

Fig. 2. ROC curves for the microRNAs hsa-miR-126-5p and hsa-miR-210-3p. ДИ — confidence interval

Рис. 2. ROC-кривые для микроРНК hsa-miR-126-5p и hsa-miR-210-3p. ДИ — доверительный интервал

The area under the curve (AUC) for the hsa-miR-126-5p microRNA was 0.59, the optimal cut-off point of ΔCt was −5.29, with sensitivity and specificity equal to 0.83 and 0.71, respectively. AUC for hsa-miR-210-3p was 0.66, the cut-off point of ΔCt was −1.75, with sensitivity and specificity equal to 0.89 and 0.71, respectively.

The other two microRNAs (hsa-miR-10b-5p and hsa-miR-130a-3p) showed no statistically significant difference in expression (p > 0.05).

Thus, changes in expression of two microRNAs (hsa-miR-126-5p and hsa-miR-210-3p) potentially reflect pathogenetic differences between the two disease forms.

Patients with plaque psoriasis were divided into two groups according to their PASI score:

mild plaque psoriasis (PASI score ≤ 10, n = 14);
moderate to severe plaque psoriasis (PASI score > 10, n = 24).

Patients with PPPP versus the plaque psoriasis group (PASI index ≤ 10) had a 68 % increase in hsa-miR-126-5p expression (p = 0.01). Patients with plaque psoriasis and a PASI score > 10 also demonstrated a 46 % increase in expression of this microRNA compared to patients with mild psoriasis (p = 0.03). There was no statistically significant difference in expression between patients with PPPP and the plaque psoriasis group with a PASI score > 10 (Fig. 3, а).

Рис. 3. Различия в экспрессии между группами: а — микроРНК hsa-miR-126-5p; б — микроРНК hsa-miR-210-3p. ПсО — бляшечный псориаз; ЛППП — ладонно-подошвенный пустулезный псориаз; PASI — Psoriasis Area and Severity Index

Fig. 3. Differences in expression between groups: а — the microRNA hsa-miR-126-5p; б — the microRNA hsa-miR-210-3p. ПсО — plaque psoriasis; ЛППП — palmoplantar pustular psoriasis; PASI — Psoriasis Area and Severity Index

Patients with PPPP versus the plaque psoriasis group (for the group with a PASI score of < 10) had a 49 % increase in hsa-miR-210-3p expression (p = 0.01). The group of plaque psoriasis patients with a PASI score > 10 showed a 10 % increase in expression of the same microRNA (p = 0.29) compared with patients with mild psoriasis. Patients in the PPPP group showed a 35 % increase in expression of hsa-miR-210-3p (p =0.05) compared with the plaque psoriasis group with a PASI score > 10 (Fig. 3, б).

There were no statistically significant differences in expression of hsa-miR-10b-5p and hsa-miR-130a-3p for the three groups (p > 0.05).

The level of microRNA expression in patients with PPPP was comparable to that in patients with more severe psoriasis.

Therefore, the findings suggest that altered expression of hsa-miR-126-5p and hsa-miR-210-3p may reflect the intensity of the systemic inflammatory response and indicate a more active disease.

Discussion

There is a lack of published data regarding microRNA expression in patients with PPPP.

R. Navarro et al. investigated the expression pattern of hsa-miR-21 and TIMP-3. A heterogeneous expression pattern was detected for this microRNA in the case of induced PPPP, which differed from non-induced psoriasis [15].

A study [16] in patients with psoriasis demonstrated an increase in expression of hsa-miR-210 in CD4⁺T cells compared with healthy volunteers. The potential mechanism involves the induction of Th17 and Th1 cell differentiation. This microRNA is known to impair the immunosuppressive function of Treg cells [17].

M.H. El-Komy et al. [18] reported increased expression of hsa-miR-210 in the affected skin and serum of patients with psoriasis compared with healthy volunteers, and suggested its potential association with IL-17.

Additionally, miR-210 was shown to regulate CXCL12 and IL-16 in myeloid-derived suppressor cells. MiR-210 manipulations alter CXCL12 expression and increase in vivo T-cell suppression. This provides direct confirmation of the miR-210 CXCL12 axis. In the skin of the palms/ soles, increased expression can enhance neutrophil and Th-cell influx, sustaining the inflammatory focus [19]. In experimental models of psoriasis, miR-210 enhances Th1/Th17 polarization and elevates the interferon-γ/IL-17 ratio, which functionally aligns with the neutrophil-Th17-dominated inflammation typically observed in acral lesions [20]. The expression of hsa-miR-126 correlates with increased disease severity and also induces keratinocyte proliferation in patients with psoriasis [21]. L. Murzina et al. [22] found that high levels of miR-126 in psoriatic keratinocytes cause plaque psoriasis to manifest as a moderate to severe disease. Higher levels correlated with treatment failure. However, R. Wu et al. [23] showed that hsa-miR-126 expression was reduced in CD4⁺ T cells of patients with psoriasis and in the model.

Thus, the suppression of SPRED1 and PIK3R2 by hsa-miR-126-5p can induce VEGF/FGF signaling through the MAPK/ERK and PI3K/AKT pathways, leading to a proangiogenic shift, increased and sustained inflammation [24]. The repression of CASP1-1 is accompanied by increased proliferation and decreased cell apoptosis [25].

The functional annotation of the investigated microRNAs was performed using the miRTarBase database [26]. Thus, the significant pathways modulated by hsa-miR-126-5p and hsa-miR-210-3p may be associated with the following processes (as defined by Gene Ontology): stress response, regulation of the MAPK (mitogen-activated protein kinase) cascade, leukocyte differentiation, response to endogenous stimuli, and the immune process.

The expression profile of the studied microRNAs in PPPP demonstrates striking similarity to the expression patterns of moderate and severe plaque psoriasis. In our study, the PPPP samples form a cluster that is clearly distinct from the mild forms of plaque psoriasis and statistically indistinguishable from the group with moderate/ severe disease. This indicates that PPPP potentially features a high built-in molecular inflammatory burden, which is not reflected in the clinical PASI grading, but manifests in the activation of the same immune programs as in more severe forms of the disease. Therefore, PPPP may represent a psoriasis phenotype where the molecular activity is disproportionately high compared to external clinical severity.

In summary, the increased expression of miR-126-5p and miR-210-3p in PPPP reflects the activation of angio-inflammatory and hypoxic adaptive programs, which form a stable inflammatory microenvironment in the acral skin. The repression of their targets promotes vascular activation, hyperkeratosis, and a Th17-dominant response, which may account for the more severe and refractory course of the acral form. These microRNAs may be considered as promising molecular markers of local pathogenetic rearrangement and potential therapeutic targets for difficult-to-treat psoriasis phenotypes.

Study limitations

The lack of data on disease severity in patients with PPPP and the small sample size are limitations of this study.

Conclusion

The study revealed differences in plasma expression of hsa-miR-126-5p and hsa-miR-210-3p in patients with PPPP compared with the plaque form of the disease. The findings may reflect the features of immune-inflammatory and angiogenic processes associated with various clinical phenotypes of psoriasis.

Despite the study limitations, the findings indicate the potential importance of microRNAs in characterizing the molecular activity of the disease. Further studies in larger samples of patients are required to clarify the diagnostic and prognostic role of the identified changes.