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An Elevated IL10 mRNA Combined with Lower TNFA mRNA Level in Active Rheumatoid Arthritis Peripheral Blood
Georgi Vasilev1,2, Viktoria Vasileva3,4, Mariana Ivanova5,6
1Laboratory of Hematopathology and Immunology, National Specialized Hospital for Active Treatment of Hematological Diseases, Plovdivsko Pole Str. No. 6, 1756 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.
Insights
This study reveals gene expression changes in rheumatoid arthritis (RA) patients. Active RA is linked to higher interleukin-10 (IL-10) and lower tumor necrosis factor-alpha (TNF-α) mRNA levels in blood.
Area of Science:
- Immunology
- Molecular Biology
- Rheumatology
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammation.
- The T helper (Th) 1/Th17/T regulatory (Treg) axis plays a crucial role in RA pathogenesis.
- Understanding gene expression patterns in RA is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the mRNA expression levels of key pro-inflammatory and immunoregulatory genes in the peripheral blood of RA patients.
- To correlate gene expression patterns with disease activity in RA.
- To elucidate the systemic imbalance in the Th1/Th17/Treg axis in RA.
Main Methods:
- Isolation of total RNA from peripheral blood samples of RA patients and healthy controls.
- Quantification of mRNA levels for eight target genes (TNFA, IL6, IL12B, IL23A, IL18, FOXP3, TGFB1, IL10) using real-time quantitative PCR with TaqMan assays.
- Analysis of gene expression correlations and differences based on disease activity.
Main Results:
- Downregulation of IL6, FOXP3, and IL12B mRNA was observed in RA patients compared to controls.
- Upregulation of IL23A mRNA was noted in RA patients.
- Active RA cases showed significantly higher IL10 and lower FOXP3 mRNA expression.
- A strong positive correlation between FOXP3 and TNFA, and a moderate correlation between FOXP3 and TGFB1 were found.
- Distinct gene expression profiles (IL10, TNFA, IL12B) could differentiate RA disease activity cohorts.
Conclusions:
- The study demonstrates a systemic imbalance in the Th1/Th17/Treg axis in RA patients.
- Elevated IL-10 and decreased TNFA mRNA levels in peripheral blood are associated with active RA.
- Gene expression profiling offers potential for classifying RA disease activity.
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