الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Rheumatoid arthritis is an autoimmune disorder that leads to persistent inflammation and in severe cases joint damage. The pathogenesis of RA is complex and among multiple pathogenic pathways is PDCs that have been activated and secrete type I interferons, which contribute to inflammation in RA patients. The two most widely studied type I interferons in rheumatic disorders are IFNα and IFNβ , Certain cells produce each subtype in response to certain inputs.
Type I interferon has the potential to be a biomarker for the expectation of response to anti-TNF therapy in RA. For example, the ratio of pretreatment IFNβ to IFNα (IFNβ/αratio) may predict responsiveness to anti-TNF medication.
Moreover, myeloid-related protein (MRP-8 and MRP-14), are intracellular Ca2+-binding proteins expressed by activated immune cells and has gained interest in many inflammatory disorders including RA. As a result, the level of circulating MRP-8/14 could be used as a biomarker for measuring clinical responses.
For the avoidance of joint degeneration, functional impairment, and a poor disease prognosis, early detection and proper treatment are important.
In the field of RA therapy methotrexate (MTX) is suggested as first-line therapy for early RA. Yet, conventional DMARDs do not work for at least 30% of patients. According to the most recent guidelines, patients who are unresponsive to first-line treatment are indicated for biologic DMARDs, most commonly TNF inhibitors. Anti-TNF treatment has been successfully used to treat RA over two decades, although one-third of patients have no response or respond poorly.
Predicting responders and non-responders to TNFi could permit earlier choice of alternative bDMARDs from the early beginning and thus enable better control of disease activity with saving time and cost.
The aim of the work was to study serum IFN-β/α ratio and serum Myeloid-related protein 8 and 14 (MRP8/14) in rheumatoid arthritis biologic naive patients prior to initiating anti-TNF therapy as predictors of response to treatment.
The study was carried on 40 Biologic naïve RA patients who were divided according to Response to anti-TNF therapy into:
• Responders (group I): 13 cases responded to treatment after six months of anti-TNF treatment.
• Non Responder (group II): 27 cases did not respond to treatment after six months of anti-TNF thereby.
Every single patient was going through: detailed history taking, DAS 28 activity score was applied to all RA patients pre and post biological anti-TNF therapy.
Laboratory tests were performed on all of the patients in the study groups: CBC, ESR, CRP, SGPT, SGOT, blood urea, serum creatinine, RF, anti-CCP, baseline levels of serum interferon β and serum interferon α and Serum myeloid-related protein 8/14 level was estimated at baseline also at week 24.
The results of the current study revealed that:
In RA, the ratio of pretreatment IFNβ to IFNα (IFNβ/α ratio) would indicate anti-TNF treatment responsiveness..
Interferon beta/ alfa ratio can significantly distinguish non-responders from responders at a cutoff level > 1.47, with a sensitivity of 85.19%, a specificity of 84.62%, and a positive predictive value of 92.0%.
In RA, the amount of circulating MRP-8/14 could be used as a biomarker to monitor clinical responses to anti-TNF medication.
The Roc curve of the serum myeloid-related protein 8/14 level shows that Serum myeloid-related protein 8/14 level can significantly distinguish non-responders from responders at a cutoff level >45.5 with a sensitivity of 88.89%, a specificity of 84.62%, and a positive predictive value of 92.3%.