الفهرس | Only 14 pages are availabe for public view |
Abstract Systemic lupus erythematosus is the most serologically and clinically diverse multisystem autoimmune disease characterized by autoantibody production, immune complex formation and immunologically mediated tissue injury. Lupus nephritis is a prominent feature in SLE present in 15-30% of patients with lupus at the time of the initial diagnosis and 30-50% during the disease progression. Now, evidence that TWEAK contributes to the pathogenesis of LN is accumulating due its role in promoting an inflammatory response, renal cell proliferation, apoptosis, vascular changes and fibrosis. This study represents one of the studies that aimed to assess the role of TWEAK in detecting the renal disease activity in patients with SLE and to study the relation between TWEAK levels as well as Fn14 with disease activity and pathological LN classification. The present study included thirty SLE patients who were selected from outpatient clinic of Physical Medicine, Rheumatology and Rehabilitation as well as Nephrology department of Ain Shams University Hospitals, diagnosed according to SLICC criteria 2012 for SLE. Summary and conclusion (157) They were divided into two groups, 15 newly diagnosed LN patients, 11 females and 4 males, their ages ranged between 18-43 years with a mean of 29.7±8.8years and 15 newly diagnosed SLE patients without renal affection, they were all females, their ages ranged between 21- 45 years with a mean age of 30.0 ± 10.1 years as well as 15 healthy individuals served as a control group. All patients were subjected to history taking, clinical examination, laboratory investigations as CBC, ESR, CRP, ANA, anti-dsDNA autoantibody, serum C3, C4, renal function tests, urine analysis and renal biopsy for the LN group as well as assessment of disease activity by SLEDAI scores. Serum and urinary levels of TWEAKwere measured in all patients and control by ELISA technique. Fn14 was detected in renal biopsies from LN patients by immunohistochemsitry. The present study revealed: A significantly higher serum TWEAK levels in patients with LN than control group. While, a significantly higher urinary TWEAK levels were found in patients with LN than non LN and control groups. A statistically significant difference between serum levels of TWEAK in patients with stroke as well as positive Summary and conclusion (158) antiphospholipid antibodies and those without, while there was no statistically significant difference with other clinical manifestations. A statistically highly significant difference between urinary levels of TWEAK in patients with hematuria, pyuria and presence of casts and those without. A significant positive correlation between serum levels of TWEAK and ESR as well as CRP levels. A significant negative correlation between TWEAK levels and C3 as well as C4 levels. Also, a significant negative correlation was noticed between urinary TWEAK levels and anti-dsDNA titres. A statistically high significant positive correlation between uTWEAK and proteinuria as well as P/C ratio. A statistically significant positive correlation between urinary levels of TWEAK and rSLEADI as well as activity index. No correlation was found between serum and urinary level of TWEAK and either age, sex or disease duration. A statistically significant positive correlation between Fn14 and P/C ratio. Summary and conclusion (159) Non significant correlation between Fn14 and different studied parameters. Our study highlighted that serum TWEAK sensitivity and specificity were 56.67% and 86.67%. While urinary TWEAK sensitivity and specificity were 53.33% and 100%, besides its association with rSLAEDI, urinary TWEAK with a cut off > 20 pg/ml can be a biomarker to diagnose patients with lupus nephritis and to detect renal disease activity. We can conclude from these results that: Being higher in patients with active LN, TWEAK might play a role in the pathogenesis of the disease. In addition to its excellent diagnostic performance for discriminating patients with lupus nephritis from other SLE patients, it might be helpful to predict the onset and progression of lupus nephritis in SLE patients and to detect renal flares as well as response to treatment but this will need further studies Recommendations (160) Recommendations 1. Serial urinary TWEAK measurements in SLE patients can be helpful to predict the onset and progression of lupus nephritis. 2. Further longitudinal larger scale studies, including more patients are recommended to investigate the role of urinary TWEAK in detecting flares and monitoring response to therapy in LN patients. 3. More research is recommended to study the correlation between the urinary TWEAK as well as Fn 14 and renal biopsy. 4. Further larger scale studies are needed to assess the specificity of uTWEAK in LN in comparison to non lupus renal patients and other glomerulopathies. 5. More research is needed to study the therapeutic role of antiTWEAK in LN. 6. Further studies to assess the role of TWEAK in platelet function and activation |