Clinical associations of autoantibodies against monomeric C-reactive protein in systemic lupus erythematosus

The aim of this study was to analyze circulating levels of anti-monomeric CRP autoantibodies [anti-mCRP] in serum samples from SLE patients in relation to biochemical and clinical disease activity markers and to identify significant associations between the presence of these antibodies and the relevant clinical manifestations of SLE. Serum levels of IgG anti-mCRP antibodies were detected by enzyme linked immunosorbent assay [ELISA] for sixty patients diagnosed as SLE and met the revised ACR criteria and 30 matched healthy subjects as a control group. Disease activity was evaluated according to the Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] score. Association of anti-mCRP reactivity with clinical features, with other auto-antibodies and with serum concentrations of C3, C4, C1q and CRP were assessed. In this study IgG antibodies to mCRP were found in sera from 65% SLE patients compared to 3.3% healthy controls. In SLE patients positive for IgG anti-mCRP antibodies, there were significantly greater frequency of renal affection [76.9% vs 28.5%, P<0.001], thrombosis /fetal loss [43.5% vs 9.5%, P<0.05], aCL IgG, aCL IgM and LAC positivity [41% vs 14.2%, 25.6% vs 14.2%, 35.8% vs 14.2%, P<0.05] and anti-dsDNA antibodies positivity [69.2% vs 42.8%, P<0.05]. Also, there were lower mean counts o/WBCs, lymphocytes, platelets, lower levels of CRP, C3, C4, C1q and higher mean of SLEDAI score in SLE patients positive to IgG anti-mCRP antibodies. Eight [20.5%] patients with IgG anti-mCRP and 4 [19%] patients without were positive for aPL antibodies without clinical manifestations of antiphospholipid syndrome [APS] [asymptomatic aPL carriers] with insignificant difference between both groups. Also, there were negative correlation between WBCs, lymphocytes, platelets counts, levels of C3, C4 and C1q with serum levels of anti-mCRP antibodies and significant positive correlation between the levels of serum aCL IgG, aCL IgM, anti-dsDNA antibodies and SLEDAI score of disease activity with serum levels of anti-mCRP antibodies. In this study we have demonstrated the high prevalence of anti-mCRP autoantibodies in SLE. Also, observed strong significant association of anti-mCRP reactivity with renal affection and thrombosis and found that the antibody levels were correlated with clinical and laboratory disease activity measures

Circulating levels of endothelin-1 in patients with systemic sclerosis: relationship to specific organs involvement

The aim of this study was to determine the serum levels of endothelin-1 [EN-1] as a marker of endothelial cell activation in patients with systemic sclerosis [SSc] and to investigate its relationship to specific organs involvement. Thirty two female patients diagnosed as SSc were included in this study; all of them met the criteria proposed by the ACR. Serum EN-1 was detected by enzyme linked immunosorbent assay [ELISA] for the patients and 20 matched healthy subjects as a control group. Thorough clinical assessment was performed; high resolution computed tomography [HRCT] scan and scoring was done for patients with pulmonary fibrosis; doppler echocardiography was done to assess pulmonary artery pressure. In this study; there was highly significant increase in the mean titre of EN-1 in SSc patients than in control group [<0.001] and significant increase in diffuse than limited SSc [P<0.05]. Significantly higher levels of Serum EN-1 were found in SSc patients complaining from pulmonary fibrosis, pulmonary and systemic arterial hypertension [P<0.001], higher in patients complaining from sclerodactyly, digital ulcers, cardiac and renal affection and in patients positive either for Anti-TOPO-I antibodies or ACA [P<0.05]. Also, there were significant positive correlation between mean pulmonary artery pressure, mean systemic arterial pressure, levels of serum creatinine, serum urea, 24 hours proteinuria, titre of ANA, anti- TOPO-I antibodies, ACA and HRCT scores with serum levels of EN-1 in SSc patients. Also, there was a significant negative correlation with creatinine clearance. Enothelin-1 through endothelial cell activation has a pathogenic role in SSc that help in evaluation of the clinical severity of scleroderma lung disease, systemic hypertension, cardiac and renal affection. EN-1 may also represent a promising serological parameter for therapeutic consideration; use of endothelin receptor antagonist may be a strategy for reaching clinical improvement

Markers of type II collagen synthesis and degradation as a predictor of radiographic progression in knee osteoarthritis

The aim of this study was to evaluate serum PIIANP and urinary CTXII as a parameters of type II collagen synthesis and degradation, respectively, in patients with OA knees and to investigate whether the use of these two molecular markers could predict the progression of joint damage evaluated by radiography during a period of 3 years. Sixty patients had symptomatic primary knee OA of Kellgren-Lawrence [K-L] grade I-III and met ACR criteria. These patients were evaluated prospectively for 3 years. Serum PIIANP and urinary CTX-II levels were measured by ELISA at baseline and at study end and their levels compared according to the changes in joint space width [JSW], K-L grade and WOMAC index, over 3 years. Also, we assessed the diagnostic value of those molecular markers and their performance for prediction of radiological progression. Serum and urinary levels also compared with 40 matched healthy subjects as a control group. There were significant decrease in the baseline serum PIIANP [P<0.001] and increase in the baseline urinary excretion of CTX-II [P<0.001] in knee OA patients in comparison with the control, in bilateral than unilateral cases [P<0.05], [P<0.05] and also with increasing the K-L radiological severity of the disease [P<0.05], [P<0.001], respectively. There were significant decrease in the mean baseline serum PIIANP and highly significant increase in the mean baseline urinary excretion of CTXII in progressors [JSW narrowing > 0.5 mm] and in patients showed increase in K-L grading either of the signal or both knees [P<0.05], [P<0.001], respectively. There were significant decrease in the mean study end serum PIIANP and highly significant increase in the mean study end urinary excretion of CTX-II in progressors [JSW narrowing > 0.5 mm] and in patients showed increase in K-L grading either of signal or both knees [P<0.05], [P<0.001], respectively. There were insignificant correlation between serum PIIANP and urinary CTX-II either at the baseline or study end and also insignificant correlation between those molecular markers with disease duration, BMI and WOMAC index [P>0.05]. Urinary CTX-II showed a higher diagnostic sensitivity and specificity [75% - 92%] than serum PIIANP [60% - 90%], respectively. The diagnostic specificity was greatest when both tests were found in combination [96%]. Also, combination of tests showed higher diagnostic sensitivity [92.3%] and specificity [55.3%] for predicting the radiological progression over 3 years than either one alone. In conclusion: using specific molecular markers serum PIIANP and urinary CTX-II, we found that patients with knee OA are characterized by depressed type II collagen synthesis and increased type II collagen degradation. Combining these two molecular markers allows the identification of patients with a high risk of subsequent progression of joint damage