Objectives Renal involvement is the most important manifestation of systemic lupus erythematosus, but assessing of inflammatory response in kidneys with non-invasive methods is still challenging. In this study we aimed to define markers of active lupus nephritis (LN) using urine immune profiling.
Methods Levels of cytokines (18-plex array) and mRNA expression (40 immune and glomerular injury genes) were measured in urine samples of LN patients with active disease (n=17), during remission (n=16), and in healthy subjects (n=19).
Results Urine levels of CCL2, CCL5, CXCL10 and IL-6 were elevated in active LN as compared to remission (best discrimination for CCL2), and correlated with LN activity. In the active disease, urinary cell transcriptome showed strong upregulation of proinflammatory cytokines (e.g. TNF, CCL2, CCL5, CXCL10), Th1 related genes (e.g. CD3G, CD4, TBX21, IFNG), and markers of glomerular damage (NPHS2 [podocin]). Active pattern of gene expression was also observed in 5 patients in remission, who had moderately increased urinary leukocyte count, two patients from this group (40%) developed renal exacerbation during following 3 months. Markers of Th17 immune axis (e.g. IL-17A) were not significantly increased in active LN.
Conclusions Active LN patients (also patients at risk of exacerbation) were characterised by marked increase of proinflammatory mediators in the urine. We identified CCL2 chemokine as the most promising marker for monitoring of disease flare.
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