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Background
Systemic lupus erythematosus (SLE) is a serious, complex, multi-system autoimmune rheumatic disease with significant variability in the phenotypes and severity of the disease. The greatest challenges continue to be the prevention and management of irreversible organ damage and active lupus nephritis (LN), one of the most feared phenotypes in SLE.
Organ damage is a primary outcome in SLE, which is accrued not only during the disease course, but also by therapy itself [1]. Early damage is more likely to be linked to active inflammation, while late irreversible damage is often attributable to the side effects of drugs and especially to chronic and cumulative corticosteroid exposure [2]. The Systemic Lupus International Collaborating Clinics/American College of Rheumatology SLICC/ACR Damage Index (SDI), divided into 38 items grouped in 12 organ systems, is a valid measure of irreversible organ damage in SLE [1]. Despite improvement in the survival of SLE patients in recent decades, significantly higher morbidity and mortality are reported in patients developing irreversible organ damage [1]. The patterns of organ damage vary among populations [3-5], but the musculoskeletal, cardiovascular, and renal systems are those most frequently affected [6]. Nowadays, prevention of irreversible damage is a major goal in the management of SLE patients and identification of the key molecules involved in the pathogenesis of organ damage is needed.
Lupus nephritis is a major manifestation associated with higher morbidity and mortality of SLE patients [7]. It has a considerable influence on treatment decisions, as well as long-term outcomes. The effective treatment of LN requires a correct diagnosis, timely intervention, and early treatment of any disease relapse. Renal biopsy is still the gold standard for diagnosis and deciding on therapy in LN but its invasive nature prevents it from being used repetitively in many cases [8]. Traditional clinical parameters such as proteinuria, glomerular filtration rate, urine sediments, anti-dsDNA antibodies, and complement levels are not sensitive or specific enough to detect activity and early relapse of LN [9, 10]. Novel serum and urinary biomarkers such as cytokines and chemokines CCL2 [11], CCL3, CCL5 [12], IL17 [11], BLyS, APRIL [13], growth factor TGF? [11] and others (TWEAK [14], IGFBP2 [15], OPG [16]) have recently been nominated for diagnosis and monitoring of LN. Although intensively investigated [17, 18], only a few...