An Elevated IL10 mRNA Combined with Lower TNFA mRNA Level in Active Rheumatoid Arthritis Peripheral Blood

Author:

Vasilev Georgi12ORCID,Vasileva Viktoria34,Ivanova Mariana56,Stanilova Spaska3ORCID,Manolova Irena3ORCID,Miteva Lyuba3ORCID

Affiliation:

1. Laboratory of Hematopathology and Immunology, National Specialized Hospital for Active Treatment of Hematological Diseases, Plovdivsko Pole Str. No. 6, 1756 Sofia, Bulgaria

2. Medical Faculty, Sofia University St. Kliment Ohridski, 1 Kozyak Str., 1407 Sofia, Bulgaria

3. Department of Molecular Biology, Immunology and Medical Genetics, Medical Faculty, Trakia University, Armeiska Str. No. 11, 6000 Stara Zagora, Bulgaria

4. Clinical Laboratory, Trakia Hospital, Dunav Str. No. 1, 6000 Stara Zagora, Bulgaria

5. Clinic of Rheumatology, University Hospital “St. Ivan Rilski”, Urvich Str. No. 13, 1612 Sofia, Bulgaria

6. Medical Faculty, Medical University-Sofia, Ivan Geshov Blvd. No. 15, 1431 Sofia, Bulgaria

Abstract

We aimed to investigate the expression of pro-inflammatory cytokine genes TNFA, IL6, IL12B, IL23, IL18 and immunoregulatory genes FOXP3, TGFB1, and IL10 in the peripheral blood of patients with rheumatoid arthritis (RA) at messenger ribonucleic acid (mRNA) level. The total RNA was isolated from peripheral blood samples. Real-time quantitative PCR was used to perform TaqMan-based assays to quantify mRNAs from 8 target genes. IL23A was upregulated (1.7-fold), whereas IL6 (5-fold), FOXP3 (4-fold), and IL12B (2.56-fold) were downregulated in patients compared to controls. In addition, we found a strong positive correlation between the expression of FOXP3 and TNFA and a moderate correlation between FOXP3 and TGFB1. These data showed the imbalance of the T helper (Th) 1/Th17/ T regulatory (Treg) axis at a systemic level in RA. In cases with active disease, the IL10 gene expression was approximately 2-fold higher; in contrast, the expression of FOXP3 was significantly decreased (3.38-fold). The main part of patients with higher disease activity expressed upregulation of IL10 and downregulation of TNFA. Different disease activity cohorts could be separated based on IL10, TNFA and IL12B expression combinations. In conclusion, our results showed that active disease is associated with an elevated IL10 and lower TNFA mRNA level in peripheral blood cells of RA patients.

Funder

“Fund for Scientific and Mobile project from Medical Faculty at the Trakia University”, Stara Zagora, Bulgaria

Bulgarian Ministry of Education and Science

Publisher

MDPI AG

Reference41 articles.

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2. Gene Expression Identifies Patients Who Develop Inflammatory Arthritis in a Clinically Suspect Arthralgia Cohort;Niemantsverdriet;Arthritis Res. Ther.,2020

3. B Cells in Rheumatoid Arthritis: Pathogenic Mechanisms and Treatment Prospects;Wu;Front. Immunol.,2021

4. Aberrant Expression of Interleukin-10 in Rheumatoid Arthritis: Relationship with IL10 Haplotypes and Autoantibodies;Valle;Cytokine,2017

5. Disease Flares in Rheumatoid Arthritis Are Associated with Joint Damage Progression and Disability: 10-Year Results from the Best Study;Markusse;Arthritis Res. Ther.,2015

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