الفهرس 
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Abstract
RA is a systemic autoimmune inflammatory disease that predominantly affects multiple peripheral joints. Although the exact mechanisms that contribute to the disease pathogenesis are still largely unknown, it is generally well accepted that numerous inflammatory cells such as T cells, B cells, fibroblast-like synoviocytes, and antigen-presenting cells and their extensive production of proinflammatory mediators, such as TNF and IL-1, are implicated. Histopathologic features of RA synovial tissue encompass infiltration by macrophages and T cells, synovial lining hyperplasia, neoangiogenesis, and pannus formation ( Scott et al., 2010).
Functionally, IL-23 has been classified as a proinflammatory mediator responsible for keeping balance between effectors and regulatory T cell response and it is a necessary factor for the development of T cell-dependent inflammation ( Izcue et al., 2008).
Increased amounts of IL-23 have been associated with the several autoimmune disease including RA, Lyme arthritis, inflammatory bowel disease, Crohn’s disease, psoriasis and multiple sclerosis (MS) ( Brentano et al., 2008).
The present study was designed to evaluate the serum level of IL-23 in patients with rheumatoid arthritis, and to evaluate its significance as a marker of disease activity and joint destruction.
Sixty patients with a clinical diagnosis of RA 48 (80 %) females and 12 (20%) males fulfilled ACR clinical criteria for RA (2010) ,were included in the study and ten healthy controls, 7 males (70%) and 3 females (30%) with a mean age of 39.30 ± 12.55 years. Patients were recruited from the Rheumatology & Rehabilitation out- patient clinic at Beni-Sweif University Hospital in the duration between September ( 2013 ) to October ( 2014 ), all subjects fulfilled the ACR 2010 classification criteria (Aletaha et al, 2010).
All patients will be subjected to the following:
• Full history taking and introduction of DMARD therapy.
• Past history of hypertension, diabetes mellitus, hyper or hypothyroidism, local joint trauma and other chronic diseases.
• Full physical examination.
• Individual disease activity was quantified using the DAS-28 (Fransen et al., 2003) and the CDAI (Aletaha and Smolen , 2005).
• Laboratory features of patients with RA (ESR, CRP, hemoglobin concentration, anti CCP, HAQ and RF positivity) were recorded.
• Radiographs of hands were obtained from patients with RA and evaluated for the presence of erosions by an experienced rheumatologist blinded to the clinical data. All subjects gave written consent to participate (Larsen , 1995).
• Measurement of serum IL-23 levels. Cytokines in the supernatants of cultures and in sera were assayed with an ELISA kit ( Yu et al., 2013).
They were 12 males (20%) and 48 females (80%); the age of our patients ranged from 25 to 75 (years) with a mean of 49.77 ± 12.06 (years) and their disease duration ranged from 25 – 31 (months) with a mean of 7.16 ± 7.29 (months).
This study demonstrated the following:
• Testing the level of serum IL-23 in our RA patients, it ranged from 0.00 to 49.30 pg/ml with a mean of 19.12 ± 13.45 pg/ml. On the other hand, the levels of IL-23 in the sera of normal controls ranged from 0.00 to 1.40 pg/ml with a mean of 0.90 ± 0.63 pg/ml. The mean serum level of IL-23 in RA patients was significantly higher than those in healthy control (P= 0.0001).
• A comparison of the mean values of IL-23 levels between the ACCP positive (22.77 ± 12.01) pg/ml and ACCP negative (2.89 ± 4.47) pg/ml patients, revealed highly significant difference between the two groups (P-value= 0.001). There was significant difference between anti-CCP positive and anti-CCP negative patients as regarding serum levels of IL-23.
• IL-23 was positively correlated with morning stiffness duration (r =0.907 , p=0.000( also there was positive correlation between IL-23 levels and both DAS-28 (r=0.967**, p=0.000) & CDAI scores (r = 0.952 , p=0.000) and all correlations were statistically significant.
• IL-23 was positively correlated with HAQ (r = 0.953 , P=0.000); and the correlation was statistically significant.
• IL-23 serum levels were highly significantly correlated with swollen joint count (r = 0.970**) with (P-value = 0.000).
• Also there was significant positive correlation between IL-23 serum levels and tender joint count (r = 0.719**) with (P-value = 0.000).
• There was positive correlation between IL-23 and both RF (r=0.917**) titer and ESR (r=0.950**) , Both correlations were statistically significant ( P-value=0.000).
• There was a positive correlation between IL-23 and CRP (r= 0.954 , P=0.001 ), the correlation was statistically significant, ( P-value=0.001).
• There was a negative correlation between IL-23 and hemoglobin concentration (r= -0.642**) , it was statistically significant,
(P=0.000).
• Serum IL-23 levels were negatively correlated with steroid dose therapy in our RA patients (r = -0.669, P-value= 0.001). Mean IL-23 was significant high in patients who never received steroid before and the difference was statistically high significant (P=0.001)
Radiologically; by studying the IL-23 serum level for patients with different RA radiological classes (Larsen score), we found that patients with x - ray class 4 have IL-23 mean value (45.40 ± 8.89) pg/ml which is higher than those with class 3 (29.84 ± 8.87) pg/ml, class 2 (32.20 ± 8.74) pg/ml, and class 1 (13.42 ± 8 ) pg/ml. There was statistical significant difference between IL-23 mean value associated with the different X ray classes.
Conclusion and Recommendations
The study demonstrates that, the serum IL-23 levels are significantly elevated in patients with RA during the active stage of the disease. The serum IL-23 level in the RA patients correlates with disease activity parameters. There are positive correlations between serum IL-23 levels and ( duration of morning stiffness , swollen joint count, tender joint count, RF, ACCP, CRP, DAS-28 , CDAI scores) , negative correlation with hemoglobin concentration. . There was statistical significant difference between IL-23 mean value associated with the different X ray classes .
The study confirmed that the circulating IL-23 concentration was much higher in RA patients than healthy controls. In addition, IL-23 is involved in disease progression and bony erosions in patients with RA. We recommend further studies on disease progression with follow up of disease treatment comparing IL-23 to see same patients during periods of activity and remission of the disease.