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Objectives Current treatments are effective only in 30% of lupus nephritis patients emphasizing the need for novel therapeutic strategies. To develop mechanistic hypotheses and explore novel biomarkers, we analyzed the longitudinal urinary proteomic profiles in patients with lupus nephritis undergoing treatment. Methods We quantified 1,000 urinary proteins in 30 patients with lupus nephritis at the time of the diagnostic renal biopsy and after 3, 6, and 12 months. The proteins and molecular pathways detected in the urine proteome were then analyzed with respect to baseline clinical features and longitudinal trajectories. The intrarenal expression of candidate biomarkers was evaluated using single cell transcriptomics of renal biopsies from lupus nephritis patients. Results Our analysis revealed multiple biological pathways including chemotaxis, neutrophil activation, platelet degranulation, and extracellular matrix organization that could be noninvasively quantified and monitored in the urine. We identified 237 urinary biomarkers associated with lupus nephritis as compared to controls without SLE. IL-16, CD163, and TGF-β mirrored intrarenal nephritis activity. Response to treatment was paralleled by a reduction of urinary IL-16, a CD4 ligand with proinflammatory and chemotactic properties. Single cell RNA sequencing independently demonstrated that IL16 is the second most expressed cytokine by most infiltrating immune cells in lupus nephritis kidneys. IL-16 producing cells were found at key sites of kidney injury. Conclusion Urine proteomics may profoundly change the diagnosis and management of lupus nephritis by noninvasively monitor active intrarenal biological pathways. These findings implicate IL-16 in lupus nephritis pathogenesis designating it as a potentially treatable target and biomarker.

It has been proposed for many years that low-level laser (or light) therapy (LLLT) can ameliorate the pain, swelling, and inflammation associated with various forms of arthritis. Light is thought to be absorbed by mitochondrial chromophores leading to an increase in adenosine triphosphate (ATP), reactive oxygen species and/or cyclic AMP production and consequent gene transcription via activation of transcription factors. However, despite many reports about the positive effects of LLLT in arthritis and in medicine in general, its use remains controversial. For all indications (including arthritis) the optimum optical parameters have been difficult to establish and so far are unknown.We tested LLLT on rats that had zymosan injected into their knee joints to induce inflammatory arthritis. We compared illumination regimens consisting of a high and low fluence (3 and 30 J/cm(2)), delivered at high and low irradiance (5 and 50 mW/cm(2)) using 810-nm laser light daily for 5 days, with the positive control of conventional corticosteroid (dexamethasone) therapy.Illumination with 810-nm laser was highly effective (almost as good as dexamethasone) at reducing swelling and a longer illumination time (10 or 100 minutes compared to 1 minute) was more important in determining effectiveness than either the total fluence delivered or the irradiance. LLLT induced reduction of joint swelling correlated with reduction in the inflammatory marker serum prostaglandin E2 (PGE2).LLLT with 810-nm laser is highly effective in treating inflammatory arthritis in this model. Longer illumination times were more effective than short times regardless of total fluence or irradiance. These data will be of value in designing clinical trials of LLLT for various arthritides.