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Abstract Summary SLE is not an uncommon disease, renal affection occurs in more than 60% in patients with SLE, and around 15% of patients with lupus nephritis progress to ESRD. Lupus nephritis is a disease with poor clinic-pathological correlation, and patients usually have ongoing immune mediated renal pathology, without clinical manifestations. The gold standard for diagnosis of lupus nephritis is renal biopsy, but being invasive and not complications free, it cannot be routinely done for proper assessment of the current state of nephritis. A reliable and non invasive tool is needed for proper monitoring of lupus nephritis, to allow modification of drug dose and duration of therapy based on the predicted outcome to improve treatment efficacy and reduce toxicity. Current laboratory markers of lupus nephritis such as anti DNA titer, proteinuria, and complement levels are unsatisfactory as they lack proper sensitivity and specificity toward renal disease. Recently, many novel biomarkers are being studied for assessing their diagnostic accuracy to lupus nephritis, and their Summary and conclusion 129 ability to predict not only renal pathology but also renal activity to allow for early intervention. Anti C1q antibodies, are auto antibodies which attack complement fraction C1q. C1q is known to have a protective role in lupus nephritis by enhancing clearance of immunogenic apoptotic bodies. Monocyte chemoattractant protein 1 (MCP-1) is a chemokine which was found to rise markedly in the urine samples of patients with lupus nephritis. Both markers were found to have good correlation with the degree of renal inflammation and the levels of traditional biomarkers of activity. In our study, we aimed at assessing the pattern of expression and diagnostic performance of both markers in patients with lupus nephritis and to highlight their renal flare predictive ability. We included 90 candidates recruited from Ain Shams University hospitals Nephrology and Rheumatology clinics and inpatient wards. Summary and conclusion 130 Patients divided into 3 groups namely; Active lupus nephritis proved by biopsy (n. 30), lupus nephritis in remission (n. 30), and healthy controls (n. 30) All lupus nephritis patients were subjected to history taking, clinical and laboratory assessment, including conventional markers of lupus activity. Patients with activity were followed up after 6 months aiming at assessing AntiC1q and uMCP-1 levels after induction immunotherapy. In addition, patients in remission were followed up for 1 year and biomarkers were measured every 4 months aiming at assessing their ability to predict renal flare if it happened during the follow up period. In the cross-sectional phase of our study both serum levels anti C1q and urine levels of MCP-1 were higher in activity group in comparison to patients in remission and to control group. Anti C1q levels were found to be higher in patients with class IV lupus nephritis than other classes, while MCP-1 levels didn’t show any significant difference regarding lupus nephritis class. AntiC1q levels correlated significantly with clinical assessment score SLEDAI, conventional biomarkers of renal Summary and conclusion 131 activity (Proteinuria, Anti DNA titer, C3, C4, ESR) and with activity index in renal biopsy. uMCP-1 levels correlated significantly with clinical assessment score SLEDAI, conventional biomarkers of renal activity (Proteinuria, Anti DNA titer, C3, C4, ESR) and with chronicity index in renal biopsy. Based on the data obtained from patients in activity and in remission, a receptor operator curve (ROC) analysis was done to define cutoff level for each marker and study its diagnostic performance in comparison to Anti DNA, C3, and C4. AntiC1q antibodies level was superior to other biomarkers with sensitivity 96.7%, specificity 70% at cut off level ≥ 26 IU/ml, while uMCP-1 levels had sensitivity of 73.3%, and specificity 63.3%. Patients in remission were followed up for a period of 1 year during levels of anti C1q and uMCP-1 were analyzed every 4 months. Five patients withdraw their consent and refused to continue the follow up phase, 2 patients died with fatal pneumonias, 23 patients completed their follow up, out of them 7 patients developed renal activity. The pattern of the biomarkers were studied in 7 patients who developed renal activity to assess whether any of the markers Summary and conclusion 132 can predict renal flare. A marker is considered a predictor if its level before renal flare exceeded its estimated cut off level from phase I of the study. Out of 7 cases with renal flare during follow up, Anti C1q titer predicted renal flare in 5 cases (71.4%), while uMCP-1 predicted only 3 cases (42.8%). Patients who developed renal flare were studied individually. It was obvious that anti C1q is a more dynamic marker than urinary MCP-1, being higher before renal activity in most cases and then gets lower gradually after treatment, while MCP-1 didn’t show any specific pattern upon which its predictive ability can be validated. 30 patients in activity were followed after induction immunotherapy, 2 patients died, the remaining 28 patients showed a dramatic DROP in the AntiC1q level after induction of remission, while uMCP-1 levels didn’t show significant change. In conclusion, both markers show significant increase in levels in cases of activity with good correlation with clinical and laboratory parameters of activity. Anti C1q is a more sensitive and specific marker than MCP-1 and other conventional biomarkers in identifying renal activity, even more its level was higher with more proliferative renal pathology. AntiC1q is more dynamic biomarker than MCP-1 and its levels can forecast renal activity and can be used in assessment of response to treatment. Summary and conclusion 133 uMCP-1 levels are affected by the chronicity of the renal disease and to the degree if renal fibrosis and its levels are not reliable alone in assessing renal activity, and cannot be used for follow up of response to treatment. |