Identification of circulating microRNA patterns in patients in psoriasis and psoriatic arthritis

Author:

Haschka Judith12ORCID,Simon David34ORCID,Bayat Sara34,Messner Zora2,Kampylafka Eleni34,Fagni Filippo34,Skalicky Susanna5,Hackl Matthias5,Resch Heinrich2,Zwerina Jochen1,Kleyer Arnd34,Cavallaro Alexander6,Sticherling Michael47,Schett Goerg34,Kocijan Roland1,Rech Juergen34

Affiliation:

1. Ludwig Boltzmann Institute of Osteology, I Medical Department at Hanusch Hospital of OEGK , Vienna, Austria

2. Karl Landsteiner Institute for Gastroenterology and Rheumatology, Rheuma-Zentrum Wien-Oberlaa , Vienna, Austria

3. Department of Internal Medicine 3 - Rheumatology and Immunology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany

4. Deutsches Zentrum Immuntherapie, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany

5. TAmiRNA GmbH , Vienna, Austria

6. Department of Radiology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany

7. Department of Dermatology, Friedrich-Alexander-Universität Erlangen-Nürnberg and Universitätsklinikum Erlangen , Erlangen, Germany

Abstract

Abstract Objective miRNAs are small non-coding RNAs that control gene expression. Specific intra- and extracellular miRNA signatures have been identified in various diseases. Whether certain miRNA signatures are associated with psoriasis (PsO) and PsA is currently unknown. We aimed to search for circulating miRNA signatures associated with PsO and PsA patients. Methods Expression of miRNAs was analysed by reverse transcription quantitative real-time PCR (RT-qPCR) in the serum of PsA, PsO patients and healthy controls. Demographic and disease-specific characteristics and imaging data from hand MRI were recorded. In the discovery phase, 192 miRNA assays were analysed in 48 samples (PsA, PsO, controls: each N = 16). For validation, 17 selected miRNAs were measured in the total population. Results A total of 141 patients and controls were analysed (51 PsA, 40 PsO, 50 controls). In the discovery phase 51 miRNAs in PsO and 64 miRNAs in PsA were down- or upregulated compared with controls, with 33 miRNAs being changed in both (adj. P < 0.05). The 17 top candidates from discovery were assessed in the validation phase, 9 of them discriminated PsA and PsO from controls [area under the curve (AUC) ≥0.70, all P < 0.05]. Four miRNAs (miR-19b-3p, miR-21-5p, miR-92a-3p and let-7b-5p) were significantly differently regulated between PsO and PsA. A combination of these miRNAs increased the AUC to 0.92 in multivariate regression model to discriminate PsO and PsA. Conclusion miRNA signatures in PsA and PsO patients differ from controls. Nine miRNAs were differentially regulated in PsA and PsO patients, five of them previously reported to be involved in bone and cartilage metabolism, indicating an intimate association of psoriatic inflammation and bone/cartilage changes.

Funder

Deutsche Forschungsgemeinschaft

Checkpoints for Resolution of Inflammation

Bundesministerium für Bildung und Forschung

BMBF

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

Reference45 articles.

1. Psoriatic arthritis from a mechanistic perspective;Schett;Nat Rev Rheumatol,2022

2. Psoriatic arthritis sine psoriasis;Olivieri;J Rheumatol Suppl,2009

3. Psoriatic arthritis: epidemiology, clinical features, course, and outcome;Gladman;Ann Rheum Dis,2005

4. Reframing immune-mediated inflammatory diseases through signature cytokine hubs;Schett;N Engl J Med,2021

5. Clinical management of psoriatic arthritis;Van den Bosch;Lancet,2018

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