Quantitative screening of active renal SLE patients’ urine for protein biomarkers using kiloplexed glass slide arrays

Abstract

Abstract Background Systemic Lupus Erythematous (SLE) is a chronic inflammatory autoimmune disease marked by flares in multiple organ systems. Leading causes of morbidity and mortality in this disease include lupus nephritis and renal failure. Because the diagnosis of lupus nephritis is currently done using kidney biopsy, noninvasive diagnostic biomarkers are crucially needed to limit the use of this costly and invasive procedure. In this effort, active renal SLE patients’ urine was interrogated for potential biomarkers using a novel quantitative antibody array based protein screen of 1000 protein targets. Methods The urine of 9 active renal (AR), 6 active non-renal (ANR) patients, and 9 healthy controls (HC) were subjected to a quantitative antibody based protein screen of 1000 unique human proteins. After creatinine normalization, dysregulated proteins were selected for further validation using group wise fold change (FC) and Mann Whitney tests. Results The quantitative array based screen of 1000 targets showed 336 proteins to be elevated in the urine of active SLE patients compared to HC. Of these, 8 proteins were elevated in the urine of AR patients compared to ANR (FC>2 P<0.05). Array results correlated well ELISA results (Spearman r > 0.6 in 60% of proteins validated thus far). Relationship of biomarkers to disease activity and renal pathology is under investigation. Conclusions We have successfully validated one of the largest targeted proteomic technologies currently available for biomarker identification. Although validation of hits as diagnostic biomarkers is still in progress, the identified proteins show promise in the noninvasive diagnosis of active renal disease in SLE patients.