MicroRNA diagnostic value in pemphigus diagnosis



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Abstract

BACKGROUND: Pemphigus is a group of life-threatening, chronic, progressive skin disease. To implement timely and adequate therapy aimed at preserving life and improving its quality, it is necessary to provide a diagnostic test confirming the diagnosis. Though various methods of diagnostics of the disease have been developed to date, many of them remain inaccessible to physicians and patients, as well as can give false-positive and false-negative results. A promising area of research is focused on microRNAs, such as miR-338-3p and miR-424-5p, which are associated with key pathogenetic processes, including regulation of apoptosis, imbalance of T-cell response and activation of autoimmune reactions.

AIMS: This study aimed to compare the expression levels of miR-338-3p and miR-424-5p in patients with pemphigus during therapy and remission, as well as in control groups of patients with other bullous skin diseases and healthy controls, and to evaluate the diagnostic value of miR-338-3p and miR-424-5p expression.

MATERIALS AND METHODS: Prospective comparative study was conducted. The study included 20 patients with active pemphigus, 15 patients in remission, 15 healthy control group participants, and 6 patients with other bullous diseases in the active stage. The expression of miRNA-338-3p and miR-424-5p was evaluated by qRT-PCR, cDNA was obtained using StemLoop technology. MicroRNA relative expression levels were analyzed based on its comparison with the expression of U6 gene using 2-ΔΔСT method.

RESULTS: The expression levels of miR-338-3p and miR-424-5p were significantly higher in patients with pemphigus active stage compared to all other groups (p < 0.001). There was a statistically significant relationship between miR-338-3p expression level and disease severity according to the PDAI index (p < 0.001), for miR-424-5p there was also a positive correlation with severity, but with a weaker relationship. ROC analysis showed high diagnostic accuracy of miR-338-3p (AUC = 0.94) and miR-424-5p (AUC = 0.93) for differentiating between patients with active pemphigus and healthy controls, with sensitivity and specificity of 95.0% and 75.0%, 95.0% and 73.3%, respectively. At week 3 from the start of glucocorticosteroid therapy, miR-338-3p levels were significantly decreased in patients in the active pemphigus (p = 0.035), whereas no statistically significant decrease in miR-424-5p was observed.

CONCLUSIONS: miR-338-3p and miR-424-5p are significant in pemphigus as potential biomarkers for diagnosis and severity grade, and the expression level of miR-338-3p can be used to determine the efficacy of pathogenetic therapy. The high diagnostic accuracy of both microRNAs determined by ROC analysis indicates the possibility of their use as biomarkers for timely detection of the disease and differential diagnosis with other bullous skin diseases.

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About the authors

Natalya P. Teplyuk

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: teplyukn@gmail.com
ORCID iD: 0000-0002-5800-4800
SPIN-code: 8013-3256

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 4/1 Bolshaya Pirogovskaya street, 119991 Moscow

Nikolai L. Shimanovsky

The Russian National Research Medical University named after N.I. Pirogov

Email: shiman@rsmu.ru
ORCID iD: 0000-0001-8887-4420
SPIN-code: 5232-8230

MD, Dr. Sci. (Med.), Professor, Corresponding member of the Russian Academy of Sciences

Russian Federation, 1-6 Ostrovitjanova street, 117997, Moscow, Russia

Tatiana A. Fedotcheva

The Russian National Research Medical University named after N.I. Pirogov

Email: tfedotcheva@mail.ru
ORCID iD: 0000-0003-4998-9991
SPIN-code: 1261-5650

MD, Dr. Sci. (Medicine), Professor

Russian Federation, 1-6 Ostrovitjanova street, 117997, Moscow, Russia

Daria V. Mak

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Author for correspondence.
Email: dariamak25@gmail.com
ORCID iD: 0000-0002-7020-0572
SPIN-code: 8204-4555

Graduate student

Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Yuliya V. Kolesova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: kolesovamsmu@gmail.com
ORCID iD: 0000-0002-3617-2555
SPIN-code: 1441-8730

MD, Cand. Sci. (Med.), Assistant Lecturer

Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Anfisa A. Lepekhova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: anfisa.lepehova@yandex.ru
ORCID iD: 0000-0002-4365-3090
SPIN-code: 3261-3520

MD, Cand. Sci. (Medicine), Associate Professor

Russian Federation, 8-2 Trubetskaya street, 119991 Moscow

Darya N. Ulchenko

The Russian National Research Medical University named after N.I. Pirogov

Email: motci@list.ru
ORCID iD: 0009-0008-1894-5746
SPIN-code: 9735-2364
Russian Federation, Moscow

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
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