الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
Rheumatoid Arthritis is an inflammatory, chronic auto immune disease that affects about half to one percent of the population. It is represented with variable clinical manifestations and characterized by chronic inflammation of synovial tissue, damage for both articular cartilage and bone. Different risk factors have been determined, including environmental and genetic factors. Nevertheless, the causative pathogenic mechanisms are still not totally understood.
The occurrence of autoreactive B and T-cells and auto antibodies production are considered as key features for RA, with anti-citrullinated protein antibodies and rheumatoid factor being the main two biomarkers. However, up to sixty percent of the early RA patients are negative for these antibodies, that often referred to as the serological gap. Although the combination of both ACPA and RF can increase the diagnostic efficiency, seronegative patients persist.
Consequently, for further improvement of RA diagnosis, numerous studies aiming for identification of novel biomarkers. In addition, biomarkers that aid in establishing prognosis, in monitoring of disease activity and in prediction of response to treatment are required. According to that, over the past few years, several new autoantibodies have been detected in RA patients, including antibodies targeting protein-arginine deiminase enzymes and carbamylated proteins.
The PAD proteins are enzymes which catalyze peptidyl-arginine conversion into peptidyl-citrulline, recently three members of PAD enzymes have been recognized as autoantigens in rheumatoid arthritis those are PAD2, PAD3, and PAD4.
The role of miRNAs in rheumatoid arthritis patients and mice models of arthritis has been studied in various researches, also some of their direct targets have been identified in experimentally or computational studies. Micro-RNAs are single‐stranded ncRNAs which are evolutionary conserved. The mature form is approximately twenty-two nucleotides in length and they are generated endogenously.
Summary, Conclusion and Recommendations
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Micro RNAs are transcribed in larger precursors and after processing are transported into the cytoplasm. The twenty-two nucleotide mature miRNAs control gene expression at posttranscriptional level through binding to its target messenger RNAs (mRNAs) and so leading to either their cleavage, degradation or repression of their translation.
Micro RNAs play a virtual role in maintaining development and function of the immune system, and may participate in the development of numerous autoimmune diseases. It has been determined by some studies that miRNA expression in rheumatoid arthritis patients responsible for regulation of synovial tissue components. Recently, a study has demonstrated that miR-155 has a significant role in synovial tissue and cells regulation.
Micro RNA-155 can also stimulate the proinflammatory components such as TNFα, TLRs, LPS, and IL-1. Expression of miR-155 is upregulated in RA synovial macrophages /monocytes and fibroblasts. Its overexpression in macrophages triggers the production of pro-inflammatory mediators, including TNFα, so miR-155 has been observed in both inflammation and remodeling pathways.
The expression and function of miR-155 in RA peripheral blood (PB) monocytes is not fully determined yet. A proportion of synovial monocytes/macrophages are considered as precursors of PB monocytes and conceivably circulate, ready for recruitment, in a primed state. In the light of this, the present study aimed to evaluate miR-155 expression and peptidyl arginine deiminase-3 antibodies in Egyptian rheumatoid arthritis patients. In addition to their potential role in disease activity and treatment outcome. The current study was conducted on 50 individuals, divided into three groups of which, group 1 included 20 early rheumatoid arthritis patients who did not receive any treatment, group 2 included 20 rheumatoid arthritis patients who received treatment and the third group included 10 healthy volunteers, matched in age and sex as a control group.
According to the present study laboratory investigations, inflammatory markers erythrocyte sedimentation rate, c-reactive protein, and disease activity were higher in early, treatment naïve, rheumatoid arthritis patients compared to other RA patients receiving treatment and healthy control group.
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Anti-PAD3 determination shows statistically significant difference in early treatment naïve RA patients than other groups (p= 0.008) where there were eight positive patients in early, treatment naïve, RA patients and only one positive patient in RA group receiving treatment and it has positive correlation with c-reactive protein level but it does not show any significant correlation with DAS-28, anti-CCP or disease activity.
Results of the present study displayed that patients in the RA group had much higher relative expression levels of PBMCs miR-155 than the control group. Additionally, in the RA group, patients with high disease activity had higher expression levels of miR-155 than those with low disease activity. This indicates that this miRNA may have participated in occurrence and development of RA and may be valuable tool as RA disease activity potential biomarkers that is also documented by the positive correlation of miR-155 relative expression levels in PBMCs with ESR and CRP in the RA group. There were no intergroup differences in age, gender, RF, anti-CCP, disease duration as regard miR-155 fold expression.
Micro RNA-155 levels are elevated in rheumatoid arthritis patient which significantly reflect changes in disease activity that was demonstrated by ROC analysis curve where at cut off >1.417 it yielded a sensitivity of 95.0% and specificity 90.0 %. MiR-155 as a predictor for clinical outcome, ROC analysis curve was also performed, whereas at cut off ≤ 0.80 it yielded a sensitivity of 66.67% and specificity 87.50%. Understanding the role of miRNAs in immune regulatory network and rheumatoid arthritis development will provide potential drug targets.