Abstract
Objective: To 1) assess IL-6 levels in the serum of patients with rheumatoid arthritis (RA). 2) study IL-6 promoter -174 G>C “single nucleotide polymorphism (SNP)” as an imminent factor for the disease development. 3) find any relation between the level of serum IL-6 cytokine and other parameters such as age, gender, clinical severity of diseases and “disease activity scores (DAS28)”. Materials & methods: This research was carried out through a case – control approach at “Ibn – Senna Teaching Hospital” in Mosul city between November 2020 and July 2021. It included 61 RA patients diagnosed according to “ACR / EULAR 2010 criteria” and 50 healthy individuals. IL-6 serum levels were ascertained by ELISA and genotyping of IL-6 promoter was accomplished by “sequence-specific primer-polymerase chain reaction (SSP-PCR)”. Results: Mean IL-6 level in RA (69.42 ng /l ± 62.99) was elevated in comparison to healthy people (14.66 ng /l ± 23.58), P < 0.001. No age or gender effects on IL-6 concentration were noted. The ideal cut-off of IL-6 for discrimination of RA with best discriminative utility compared to healthy controls was 22.80 ng/l. At this value the IL-6 sensitivity was 91.8%, specificity 82.0% and accuracy rate 73.80%. G/G genotype was the most pervasive genotype in both RA patients and controls (70.5% in RA and 64% in healthy controls). However, it did not seem to be a risk factor for RA development compared to G/C or C/C genotypes “(OR = 1.3438, 95% CI=0.605-2.984,P=0.469)”. The mean IL-6 level in patients with GG genotype was (73.70 ng / l ± 71.09) compared to (58.37 ng /l ± 37.86) in patients with GC genotype. There was no significant difference in the IL-6 level between patients with GG and patients with GC genotypes (P = 0.2375). Although higher IL-6 mean concentration was reported in severe RA, however, no significant difference was found between patients with mild, moderate and severe RA respectively. No correlation of serum levels of IL-6 with genetic promoter polymorphism, clinical severity of diseases or DAS 28 score were reported. Conclusion: The concentration of serum IL-6 was elevated in RA in regard to healthy controls which confirmed its pivotal role in RA pathogenesis. Our data did not support the role of IL-6 promoter -174 G> C polymorphism as a risk factor for RA, nor seem to play a major role in the increase of IL-6 level among our patients with RA.
Highlights
Rheumatoid arthritis (RA) is one of the autoimmune diseases that primarily affects small synovial joints causing synovitis, progressive cartilage destruction, bone loss, and joints deformities[1]
The age of RA patients varied from 19 - 81 years (49.67 ± 13.54) in comparison to 21 -77 years (45.88 ± 15.26) in healthy controls (P=0.1538)
We suggested that the induction and increase concentration of IL-6 in both the sera and the joint fluids of RA patients are due to a plethora of cumulative effects of various chemical, physiological and immunological compounds including inflammatory cytokines such as TNFalpha and IL-1 rather than attributed to genetic differences in IL-6 promoter
Summary
Rheumatoid arthritis (RA) is one of the autoimmune diseases that primarily affects small synovial joints causing synovitis, progressive cartilage destruction, bone loss, and joints deformities[1]. The exact cause of RA remains unascertained, various etiological factors including genetic, familial, hormonal, immunological, environmental and infectious variables have all been postulated 3. In addition to protein disturbances, several genetic “single nucleotide polymorphisms (SNP)” in IL-6 promoter area or within IL-6 gene have been studied as possible risk targets. Few studies in Iraq have addressed the role of IL6 cytokine in RA pathogenesis 6-8. Among these studies only one study explore the effect of IL-6 promoter SNP at -174 G>C position 7. The data about the IL-6 cytokine (whether at protein or genetic levels) are still lacking among our patients. 2) To detect SNP at -174 (G>C) position” of IL-6 promoter area as a risk factor for diseases development. The present study was conducted to achieve the following aims: 1) To investigate the serum concentrations of IL-6 in patients with RA in Mosul city and to compare them to healthy controls through a case - control study. 2) To detect SNP at -174 (G>C) position” of IL-6 promoter area as a risk factor for diseases development. 3) To study any affiliation between IL-6 serum level and IL-6 -174 SNP and to report any correlation between IL-6 level and other parameters such as age, gender, clinical severity of RA and DAS 28 scores
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