Anti-cyclic citrullinated peptide antibodies in rheumatoid arthritis and their clinical significance

One of the characteristics of rheumatoid arthritis [RA] is the presence of several autoantibodies in the serum of the patient. However, most of these antibodies have failed to demonstrate adequate diagnostic and prognostic value so far. There is growing evidence that therapeutic intervention early in the course of RA leads to earlier disease control less joint damage, and a better prognosis. A new serological test, the anti-cyclic citrollinated peptide [anti-CCP] was developed. Anti-CCP was reported to have a high specificity for the diagnosis of RA, especially in patients with early disease and its presence before disease presentation is suggestive of its role in disease pathogenesis .The aim of this study is to estimate the level of anti-CCP antibodies in the serum of RA patients and to correlate them with RF isotypes [IgG and IgM] and clinical findings as disease activity and severity. This study comprised 68 RA patients [64 female and 4 males] diagnosed according to the revised criteria described by ACR [1987], in addition to 15 healthy control subjects. Clinical assessment of RA disease activity and severity, radiological investigations, and laboratory investigations [complete blood picture, ESR, CRP, determination of anti-CCP, IgG-RF and IgM-RF antibodies by ELISA technique] were done for all subjects.Highly significant increase in the levels of anti-CCP, IgG-RF and IgM-RF antibodies were found in RA patients compared to control group [P<0.001 for each]. Anti-CCP antibodies showed the highest diagnostic specificity [100%] than both RF IgM and IgG [93.33% for each].The anti-CCP and IgG-RF tests had excellent sensitivity [95.59% and 98.53% respectively] while IgM-RF had relatively lower sensitivity than both tests [86.76%]. Anti-CCP level was significant positively correlated with duration of the disease [P=0.024].Also,there was positive correlation between anti-CCP levels and all disease activity parameters which include the number of active joints [P=0.007], duration of morning stiffness [P<0.001], ESR [P<0.001] and CRP values [P=0.024]. Anti-CCP test had the best correlation with disease activity grades .disease severity, and radiological score [P=<0.001, P=<0.001 and P=0.000 respectively]. The level of anti-CCP in patients receiving methotrexate either alone or with lefwnomide is lower than other patients receiving methotrexate with corticosteroids [56.5 +/- 41.33,112 +/- 95.04 lU/ml respectively]. In conclusion, anti-CCP antibodies could be regarded as a new diagnostic marker for RA as they have 100% specificity and 95.8% sensitivity and it could predict erosive development early in the disease, and it could be used in evaluation of disease activity, severity and therapeutic response

Proinflammatory cytokines [IL-12 and IL-18] in immune rheumatic diseases: relation with disease activity and autoantibodies production

lnterleukin-18 [IL-18] and its inducer IL-12 have multiple biological activities that are important in generating Th1 responses and inflammatory tissue damage. We investigated serum concentration of the novel pro-inflammatory Th1 cytokine; IL-18, and its inducer IL-12 in patients with immune rheumatic diseases. Group I comprised 32 patients of systemic lupus erythmatosus [SLE], Group II comprised 36 patients of rheumatoid arthritis [RA]. Group III comprised 9 patients [2 patients of Behcet, 2 patients of Dermatomyositis, 2 patients of Sicca syndrome, one patient of Scleroderma, and 2 patients of Mixed connective tissue disease]. Group IV is a control group consists of 21 sex and age matched healthy subjects and correlated their levels with autoantibody concentration [ANA and ds-DNA], clinical grades and SLE disease activity index [SLEDAI]. Serum IL-18, IL-12 ,ANA and ds-DNA were measured by enzyme immune sorbent assay. IL-18, IL-12 and ANA were significantly higher in the three studied groups than in the control group [IL-18; P<0.001 in the three groups, IL-12; P=0.019, P=0.002, and P= 0.006, and ANA; PO.001, P=0.002,and P=0.006, respectively].ds-DNA was significantly higher in SLE patients than in control group [P<0.001].There were significant positive correlations between; A] levels of IL-18,and both ANA and ds-DNA in SLE patient [r=0.41,P=0.001, r= 0.58 and P=0.001 respectively]; and B] IL-18 and ANA in both RA and group III patients [r= 0.32, P=0.005,r=0.61 and P= 0.022 respectively]. Also, there were significant positive correlation between the levels of IL-18 and clinical grades of the three groups [r=0.60, P=0.001, r=0.79, P=0.001, r=0.78 and P= 0.001 respectively]. In SLE patients ,IL-18 concentration shows significant positive correlation with SLEDAI score [r= 0.76 ,P=0.001]. In conclusion, the elevation of proinflammatory cytokines [IL-18 and IL-12] may trigger the inflammatory process in immune rheumatic diseases and IL-18 is correlated with disease activity

Serum levels of interleukin 1 beta and interleukin 1 receptor antagonist in patients with diabetes mellitus. Associations with microvascular complications

To better understand the potential association of serum levels of interleukin- I beta [IL-1B] and interleukin-1 receptor antagonist [IL-1ra] with diabetic rnicroangiopathy, serum concentrations of IL-1B and IL-1ra were determined in 42 patients with diabetes mellitus [22 non Insulin dependent diabetes mellitus [NIDDM] and 20 insulin dependent diabetes mellitus [IDDM]] presenting with varying degrees of diabetic status and late complications. They were compared with 26 age and sex matched healthy subjects. Our results revealed that the concentrations of IL-1B and IL-1ra were elevated in diabetic patients versus control [Mean +/- SE 0.9 +/- 0.25pg /ml for IL-1B and 752.8 +/- 53.7pg / ml for IL-1ra in diabetics vs 0.08 +/- 0.04pg /ml for IL-1B and 446.6 +/- 40.5pg /ml for IL-1ra in the control, P = 0.01 and P< 0.0001 respectively]. Patients with diabetic retinopathy [n = 16] had the highest concentrations of serum IL-1B compared to those with neuropathy [n = 14] and to those with uncomplicated diabetes [n = 12] [Mean +/- SE 1.78 +/- 0.54pg /ml vs 0.37 +/- 0.32pg /ml and 0.35 +/- 0.16 pg /ml respectively, P = 0.05] IL-1ra levels were the highest In patients with diabetic neuropathy compared to those with retinopathy and uncomplicated diabetics [Mean +/- SE 905.9 +/- 95.2pg /ml vs 749.9 +/- 93.9pg /ml and 578.02 +/- 61.8pg/ml respectively. P<0.05]. Patients with proliferative diabetic retinopathy [n = 10] had significantly higher levels of IL-1B compared to those with non proliferative retinopathy [n= 6] [Mean +/- SE 2.7 +/- 0.71pg /ml vs 0.23 +/- 0.15pg /ml, P< 0.01]. IL-1ra / IL-1B ratio was lowest in patients with diabetic retinopathy especially the prolifertive type and highest in those with neuropathy with uncomplicated diabetics having intermediate values comparable to that of the control [P>0.01], Analyzing pooled data from diabetic patients, a weak negative correlation was found between IL-1B and IL-1ra [r = - 0.22, P> 0.05]. Interstirigly IL-lB was significantly correlated with HDL-cholesterol whereas IL-1ra was significantly correlated with serum triglycerides. IL-1ra/IL-1B ratio was significantly correlated with serum total cholesterol and HDL cholesterol. [r= 0.36 r = 0.38, r = 0.35 and r =-0.34 respectively]. Serum levels of IL-B and IL-1ra are elevated in diabetic patients with and without microangiopathy reflecting ongoing inflammation and macrophage endothelial cell activation. Elevated levels of IL-1B and decreased IL-1ra/IL-1B ratio point more to proliferative retinopathy whereas high levels of IL-1ra and IL-1ra/IL-1B ratio may give an idea about the presence of neuropathy