Profiling Blood Serum Extracellular Vesicles in Plaque Psoriasis and Psoriatic Arthritis Patients Reveals Potential Disease Biomarkers

Abstract

Psoriasis vulgaris (PsV) and psoriatic arthritis (PsA) are inflammatory diseases with unresolved pathophysiological aspects. Extracellular vesicles (EVs) play an important role in intercellular communication. We compared the miRNA contents and surface proteome of the EVs in the blood serum of PsV and PsA patients to healthy controls. Size-exclusion chromatography was used to isolate EVs from the blood serum of 12 PsV patients, 12 PsA patients and 12 healthy control subjects. EV samples were characterized and RNA sequencing was used to identify differentially enriched EV-bound miRNAs. We found 212 differentially enriched EV-bound miRNAs present in both PsV and PsA groups—a total of 13 miRNAs at FDR ≤ 0.05. The predicted target genes of these miRNAs were significantly related to lesser known but potentially disease-relevant pathways. The EV array revealed that PsV patient EV samples were significantly enriched with CD9 EV-marker compared to controls. Analysis of EV-bound miRNAs suggests that signaling via EVs in the blood serum could play a role in the pathophysiological processes of PsV and PsA. EVs may be able to fill the void in clinically applicable diagnostic and prognostic biomarkers for PsV and PsA.

Towards Personalized Medicine in Psoriasis: Current Progress

“… 122 miRNAs seem to play a key role also in psoriatic arthritis (PsA) as suggested by Lättekivi et al who compared the miRNA in 12 psoriasis patients, 12 PsA patients and 12 healthy control subjects founding 212 different miRNAs in both psoriasis and PsA groups compared with healthy cohort. 123 A possible therapeutic approach using miRNAs was reported by Wu et al who showed that both miR-210 ablation in mice and inhibition of miR-210 by intradermal injection of antagomir-210 blocked the immune imbalance and the development of psoriasis-like inflammation in an imiquimod-induced or IL-23-induced psoriasis-like mouse model. 124 Thus, miRNAs seem to be promising biomarkers of prognosis, diagnosis and treatment response in psoriasis.…”

Extracellular vesicles from keratinocytes and other skin‐related cells in psoriasis: A review

“…21 Although there was no correlation between the total amount of serum EVs and the severity of psoriasis, the potential of EVs as diagnostic biomarkers for comorbidities is under investigation. 16,22 EVs also have potential as carriers for miRNAs and other targeted medicines for the treatment of psoriasis. 23 In this review, we mainly focus on EVs derived from skin-related cells and summarize their roles and possible functions in the pathogenesis of psoriasis (Figure 1), with the aim of determining novel future research directions for clinical and scientific research in the field of psoriasis.…”

“…• The effects of adipose-derived EVs in psoriasis remain unclear potential of EVs as diagnostic biomarkers for comorbidities is under investigation. 16,22 EVs also have potential as carriers for miRNAs and other targeted medicines for the treatment of psoriasis. 23 We categorized skin derived EVs based on their specific cellular origins and reviewed their roles in the pathogenesis of psoriasis (Table 1).…”

“…EVs have been identified to play important immunomodulatory roles in the development of various inflammatory skin disorders, including as psoriasis, 16 atopic dermatitis (AD), lichen planus (LP), 17,18 bullous pemphigoid (BP), 19 systemic lupus erythematosus (SLE) 20 and chronic wound healing 17 . A study revealed elevated serum‐derived IL‐17A‐producing small EVs in patients with psoriasis compared with healthy people, and IL‐17A exosome levels were significantly higher in patients with moderate‐to‐severe psoriasis compared with those with mild psoriasis 21 .…”

“…A study revealed elevated serum‐derived IL‐17A‐producing small EVs in patients with psoriasis compared with healthy people, and IL‐17A exosome levels were significantly higher in patients with moderate‐to‐severe psoriasis compared with those with mild psoriasis 21 . Although there was no correlation between the total amount of serum EVs and the severity of psoriasis, the potential of EVs as diagnostic biomarkers for comorbidities is under investigation 16,22 . EVs also have potential as carriers for miRNAs and other targeted medicines for the treatment of psoriasis 23 …”