الفهرس 
New Concepts in Lupus PathogenesisOnly 14 pages are availabe for public view
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Abstract
Systemic lupus erythematosus is a chronic multisystem autoimmune disease with a broad range of clinical manifestations. Evidence is accumulating for endothelial cell dysfunction as one of the main factors initiating vessel wall damage in SLE.
Thrombomodulin (TM) is a membrane-bound protein normally expressed on the surface of intact ECs. TM on vascular ECs is an important molecule in human natural anticoagulation system. TM acts as a thrombin receptor on the surface of vascular ECs. The binding of TM to thrombin inhibits the thrombin’s effect in conversion of fibrinogen to fibrin, and activation of coagulation factor V, VIII and platelet. Thrombin-TM complex catalyzes the activation of PC about 1000 times faster than free thrombin. APC proteolytically inactivates the coagulation cofactor Va and VIIIa, thereby inhibiting the amplification of the coagulation system.
In addition to membrane-bound TM, there is a soluble TM (sTM) form in plasma, which results from endothelial damage. It is released into serum by proteolytic degradation of ECs after injury by oxidative stress products, such as H2O2, or by activated leukocytes.
The present study aimed to assess serum concentrations of sTM and its association to different laboratory findings in SLE patients, and whether it has a role in assessing disease activity in SLE. All subjects involved in this study were free from any other conditions that can affect sTM level, such as sepsis and malignancy. The study included sixty patients diagnosed as having SLE, in addition to 30 age and sex matched healthy controls; SLE Patients were divided according to disease activity into two groups: inactive SLE group including 20 patients and active SLE group including 40 patients, who were further subdivided into: active SLE with nephritis subgroup (n=28) and active SLE without nephritis subgroup (n=12). Moreover, all SLE patients without renal affection, and regardless of disease activity, were grouped into an additional subgroup, the kidney sparing SLE subgroup (n=32, 20 inactive patients + 12 active patients without nephritis).
Patients under study were subjected to full history taking, full clinical examination and laboratory investigations including CBC, kidney function tests (serum creatinine, BUN, pr/cr ratio); anti-dsDNA titre, ESR, C3 and C4 levels as well as SLEDAI score for evaluating the disease activity. In addition, all patients and controls were assessed for serum sTM levels using a commercially available ELISA kit.
The study has demonstrated that active SLE group had a highly significant increase in serum sTM level than the inactive patients or the control group. Active patients also demonstrated statistically highly significant positive association of serum sTM levels to SLEDAI score. A highly significant increase of serum sTM levels among lupus nephritis (LN) group has also been demonstrated in comparison to kidney sparing group. This finding was found to be preserved in active patients with LN when compared to active patients without LN.
Diagnostic performance study using ROC curve analysis and multiple cut-off level for prediction of disease activity revealed that an optimum cut-off level of >600 pg/mL was the best to predict SLE activity with diagnostic sensitivity, specificity, predictive positive and negative values and efficacy of (87.5%, 95%, 97.2%,79.2% and 90%, respectively). Additionally, serum sTM level at an optimum cut-off level of >800 pg/mL was the best to discriminate LN from those without, with diagnostic sensitivity, specificity, predictive positive and negative values and efficacy of (96.4%, 83.3%, 93%, 91% and 92.5%, respectively).
In conclusion, the present study is suggestive for the role of serum sTM as indicator of endothelial damage, which may occurs in the pathogenesis of SLE especially with renal involvement. Serum sTM appears to be useful in assessing disease activity in SLE and degree of renal affection. Also, it may help in predicting flare and vascular complications or monitoring the successful therapeutic response.