الفهرس 
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Abstract
The current study was carried on fifty RA patients (41females and 9 males) from rheumatology outpatient clinic and rheumatology unit of Internal Medicine Department of Assiut University Hospital. All patients fulfilled the 2010 American College of Rheumatology criteria for RA. Also twenty healthy subjects age and sex matched were enrolled as controls. Informed consents were taken from all subjects and the study was approved by ethical committee of Faculty of Medicine of Assiut University.
Patients of RA with infection, hepatic or renal disease, and secondary osteoarthritis were excluded from the study.
Patients were divided into two groups according to disease activity score-28 as:
• Patients with severely active disease (DAS28 > 5.1); they were 29 patients.
• Patients with moderately active disease (DAS28 > 3.2 and ≤ 5.1);they were 21 patients.
Non of our patients received disease modifying agents or corticosteroids before enrollment in the study.
Twenty five patients were treated by leflunomide oral tablets initially 100 mg for 3 days then 20 mg daily, with NSAIDS for 3 months.
All patients evaluated at zero time and 25 patients after 3 months of leflunomide treatment.
All studied patients were subjected to:
• Full history and through clinical examination
• The following investigations were done for patients and controls(ESR,CRP, CBC ,RF, ,anti-CCP antibodies,Liver enzymes ,kidney function tests, Cartilage Oligomeric Matrix Protein (COMP) ,C1q ,C3 ,C4 ,MBL ,Anti-MBL antibodies).
• X-Ray to hands and feet.
• Results of the study showed that the mean of disease duration in patients was (4.78 ± SD 3.02) months , number of tender joints (22.48 ± 5.76), number of swollen joints (5.60 ± 8.46), Ritchie articular index (RAI) ( 19.04 ± 4.72),DAS-28 (5.73 ± 1.06).
• CRP and ESR were found significantly higher in studied patients compared with controls(P <0.001).
• The study revealed that 80% of patients had positive RF (40 individuals) and 20% were seronegative (10 patients) also, the study showed that 88% of patients had positive anti-CCP (44 patients) and only 12% had negative values(6 patients) at the time of diagnosis.
• Results of x-ray findings revealed that 20 patients(40%) were found to have abnormal JSN score with a mean ± SD (15.92 ± 20.96).while 21 patients (42%) had abnormal erosion score (mean ± SD 19.76 ± 25.04).
• The results of cartilage turnover assessed by COMP assays in the serum showed significantly higher levels in patients than controls{means(3.19 ± SD 2.63),(2.33 ± 0.99)}ug/L respectively(P 0.046).
• Mannose binding lectin (MBL) has been found in activation of complement system and intense inflammatory response in flare of RA. MBL was found lower in the studied patients’ with a mean ±SD (77.43 ± 57.89) ug/L than controls (108.95±108.29) ug/L but the difference is not statistically significant (P 0.346). Meanwhile the Anti-MBL antibodies were significantly higher in patients than controls with a mean ±SD (524.74 ± 299.39),(128.60± 118.60 ) ng/ml respectively (P< 0.001).
• Regarding complement activation the study revealed that the serum levels of C1q were higher in patients than controls means ±SD (70.70 ± 40.31) , (67.90 ± 32.52) ug/ml respectively however the difference was insignificant (P 0.953).On the other hand the mean levels of serum C3 were significantly lower in patients than controls with means ±SD (0.95 ± 0.47) ,(1.60 ± 0.41) mg/ml respectively (P <0.001).serum C4 levels showed no difference between patients and controls.
• Comparing moderately and severely active groups as regard disease duration, number of swollen and/or tender joints and RAI showing statistically significantly higher number of tender joints mean ± SD (24.28 ± 3.92)(P 0.015)and significantly higher RAI(22.28 ± 2.55 ) (P 0.000)in severely active group than the moderately active one mean ± SD (20.00 ± 6.99 )(14.57 ± 3.04) respectively but no statistically significant difference as regard disease duration or number of swollen joints .
• Comparing the two groups show higher serum levels of CRP, ESR 1st hour, ESR 2nd hour , RF and Anti-CCP in severely active group than the moderately active one but the difference is statistically insignificant.
• There was higher serum levels of COMP in severely active group than the moderately active one but the difference is statistically insignificant.
• Comparing both groups show statistically significant higher values of MBL mean ± SD (92.21 ± 67.97) (P 0.004) in group of severe activity than the group of moderate activity mean ± SD (57.02 ± 31.47), and Anti-MBL mean ± SD(657.66 ± 289.95)in severely active group than the moderately active one(343.57 ± 204.52 )(P 0.000).
• Comparing both groups results show no statistically significant difference as regard C1q , C3 or C4.
• Comparing patients before and after treatment showed statistically significant improvement of patients after receiving treatment as regard No. of tender joints, No. of swollen joints, DAS- 28 score& RAI.
• Comparing CRP, ESR, RF& Anti-CCP levels in patients before and after treatment showed statistically significant improvement of patients after receiving treatment as regard serum levels of CRP ,ESR 1st hour ,ESR 2nd hour, Anti-CCP but as regard RF there is statistically insignificant improvement following treatment (P 0.057).
• The serum levels of COMP decreased significantly after treatment, the mean COMP before treatment was (3.03 ± 1.35) and after treatment (2.20 ± 1.16) (P 0.004).
• The mean serum Anti-MBL decreased significantly after treatment. (before treatment was 531.60 ± 274.66) and (after treatment 196.35 ± 173.91) (P <0.001), while serum levels of C3 increased significantly after treatment, mean C3 before treatment was (1.07 ± 0.49) and after treatment (1.61 ± 0.49 after) (P 0.001) .On the other hand the mean levels of MBL, C1q and C4 showed no significant difference before and after treatment.
• The Anti-CCP levels was found positively correlated with RF levels (r-value 0.386, P-value 0.006) but not correlated to age, duration of disease , DAS 28 score, CRP ,ESR( 1st hour, 2nd hour)nor JSN and erosion scores of X-ray findings of the joints involved using modified Sharp score.
• The COMP levels was found positively correlated with JSN(r 0.832, P <0.001) and erosion score (r0.863, P< 0.001) of X-ray and negatively correlated with RF(r-0.313, P< 0.027) but not correlated to age, duration of disease ,DAS 28 score, CRP,ESR 1st hour, ESR 2nd hour nor Anti-CCP.
• The MBL levels was found positively correlated with DAS 28 score (r0.299, P< 0.035), erosion score of X-ray findings of the joints involved using modified Sharp score (r0.291, P< 0.040),and Anti-CCP (r0.285, P< 0.045) but not correlated with age, duration of the disease, CRP, ESR 1st hour, ESR 2nd hour, JSN score nor RF.
• The Anti-MBL levels was found positively correlated with DAS 28 score (r0.460, P< 0.001), but not correlated with age, duration of the disease, JSN, erosion scores of X-ray findings of the joints involved using modified Sharp score , CRP , ESR 1st hour, ESR 2nd hour, RF nor Anti-CCP.
• The C3 levels was found positively correlated with C4 levels (r0.529 , P< 0.000) but no correlation between levels of C1q,C3,C4 and levels of MBL and Anti-MBL.
Conclusion and Recommendations
Cartilage Oligomeric Matrix Protein (COMP) has been shown to be beneficial in detection of cartilage damage early in the disease and hence the need to use aggressive therapy to prevent bone and cartilage destruction in rheumatoid arthritis.Also COMP can be used to monitor the response to treatment, as evidenced by its statistically significant decreased level after treatment with leflunomide.
Mannan binding lectin (MBL) is found positively correlated to DAS 28 score, and erosion score of X-ray findings of the joints involved using modified Sharp score.This may indicate that MBL can be used as a prognostic factor in rheumatoid arthritis. The current study revealed that the mean anti-MBL antibody was significantly higher in RA patients’ than controls and it was positively correlated with DAS 28 score .This supports the role of these antibodies in diagnosis of early cases of rheumatoid arthritis and could be used as a marker for disease severity.
We found statistically significant decrease in serum levels of anti-MBL antibodies after receiving leflunomide for 3 months so these antibodies might be useful biomarker in follow up therapy of rheumatoid arthritis.
Recommendations:
1- We recommend measurement of serum COMP as a simple and a non invasive screening test for early preclinical detection of cartilage damage in rheumatoid arthritis patients.
2- As serum COMP decreased by treatment by DMARDs so it can be a useful method for follow up of treatment response.