الفهرس 
Rheumatoid ArthritisOnly 14 pages are availabe for public view
 |  | from | 169 |  |  |
| | | from | 169 | | |
Abstract
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. It mainly affects the joints in addition to other organs such as lungs, heart, and eyes. The severity of RA varies widely from mild illness to severe destruction of joints with resultant chronic pain and deformity.
The exact cause of RA is unknown. The most accepted theory is that there is an interaction between patient’s genotype and environmental triggers such as smoking, certain infections, and vitamin deficiencies.
The global age-standardized prevalence rate is higher in women, increasing with age and peaking between 75 to 79 years in women and 70 to 74 years in men in 2017.
In addition to the clinical diagnosis of RA, serologic tests are also important parameters for its diagnosis. The two serologic markers rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP) show the highest diagnostic value for RA. However, one third of RA patients remain sero-negatine for the two markers and still, there is a need for novel biomarkers in order to improve RA diagnosis.
MicroRNAs (miRNAs) are non-coding RNAs that bind target messenger RNA and control protein expression (post-transcriptional regulation). There are more than1500 miRNAs reported for humans, with more than 300 miRNAs associated with various diseases.
MiRNA-146a was first described in human acute monocytic leukemia cell line by Taganov et al., (2006) who identified its role as a negative regulator of inflammation.
In RA, miR-146a expression was reported to be upregulated in synovial tissues, peripheral blood-derived mononuclear cells and lymphocytes. Despite its elevated expression, miR-146a was non-functioning.
Whole blood sampling has clear advantages for usage in detection of changes in miRNA expression in patients with RA because it is widely available and requires only minimal manipulation.
The most sensitive and specific absolute quantification method for miRNA is quantitative real time PCR (qRT-PCR) and its two variants, stem-loop (TaqMan probe based) RT-PCR and poly (A)-tailed (SYBR green based) RT-PCR.
The study enrolled 50 Egyptian subjects divided into a patient group,
which comprised 25 RA patients, and a control group which comprised 25 healthy individuals.
The disease activity for the patients’ group was determined by simplified disease activity index.
Relative quantification of miR-146a expression in whole blood was determined using reverse tran-
scriptase quantitative real time polymerase chain reactio
The study enrolled 50 Egyptian subjects divided into a patient group,
which comprised 25 RA patients, and a control group which comprised 25 healthy individuals.
The disease activity for the patients’ group was determined by simplified disease activity index.
Relative quantification of miR-146a expression in whole blood was determined using reverse tran-
scriptase quantitative real time polymerase chain reactio
The study enrolled 50 Egyptian subjects divided into a patient group,
which comprised 25 RA patients, and a control group which comprised 25 healthy individuals.
The disease activity for the patients’ group was determined by simplified disease activity index.
Relative quantification of miR-146a expression in whole blood was determined using reverse tran-
scriptase quantitative real time polymerase chain reactio
Our study enrolled 50 Egyptian subjects divided into a patient group, which comprised 25 RA patients, and a control group which comprised 25 healthy individuals. The disease activity for the patients’ group was determined by simplified disease activity index. Relative quantification of miR-146a expression in whole blood was determined using reverse tran-scriptase quantitative real time polymerase chain reaction.
There were highly statistically significant differences between patients and healthy controls as regards relative miR-146a expression, ESR and anti-CCP (p < 0.001).
Highly statistically significant differences (p < 0.001) were also found between different subgroups of patients as regards relative miR-146a expression and ESR. MiRNA-146a levels correlated positively with those of ESR, CRP and anti-CCP (p < 0.001).
MiRNA-146a illustrated best performance in diagnosing RA, showing the highest sensitivity and specificity (96% and 100%, respectively) (AUC: 0.992 at a cut off value of 2.16) compared to anti-CCP (sensitivity: 68%, specificity: 100% and AUC: 0.87 at a cut off value of 22U/ ml) and RF (sensitivity: 56%, specificity: 80% and AUC: 0.992 at a cut off value of 13U/ml).
Conclusion
The present study demonstrated that:
• Whole blood sample could be easy reliable sample for the relative microRNA-146a (miR-146a) expression.
• MiR-146a could serve as potential biomarker for diagnosis of RA and its diagnostic performance is better than anti-cyclic citrullinated peptide and rheumatoid factor.
• Although the relative miR-146a expression was positively correlated with the disease activity of RA, its use clinically in the routine follow up of disease activity is doubtful because it is still more labor intensive and expensive than other tests used for follow up such as erythrocyte sedimentation rate and C-reactive protein.
Recommendations
The present study recommends the following:
• Larger scale studies are needed to further investigate the efficacy of miRNA-146a as a biomarker for both early disease diagnosis and response to therapy.
• Studies are needed to investigate the potential role of miR-146a mimics in the therapy of RA.
• Studies to investigate the simultaneous use of more than one miRNA as biomarkers for RA are recommended in order to increase sensitivity and specificity of disease detection.
• In settings with limited resources, more cost effective diagnosic testing procedures than quantitative real time PCR with high diagnostic efficiency are needed in the routine diagnosis of RA.
• Investigating the role of miRNAs in screening of at-risk first-degree relatives of RA patients.