Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus

Abstract

There is increased interest in using microRNAs (miRNAs) as biomarkers in different diseases. Present in body fluids, it is controversial whether or not they are mainly enclosed in exosomes, thus we studied if urinary miRNAs are concentrated inside exosomes and if the presence of systemic lupus erythematosus with or without lupus nephritis modifies their distribution pattern. We quantified specific miRNAs in urine of patients with systemic lupus erythematosus (n = 38) and healthy controls (n = 12) by quantitative reverse-transcription PCR in cell-free urine, exosome-depleted supernatant and exosome pellet obtained by ultracentrifugation. In control group, miR-335* and miR-302d were consistently higher in exosomes than in exosome-depleted supernatant, and miR-200c and miR-146a were higher in cell-free fraction. In lupus patients, all urinary miRNAs tested were mainly in exosomes with lower levels outside them (p<0.05 and p<0.01, respectively). This pattern is especially relevant in patients with active lupus nephritis compared to the control group or to the SLE patients in absence of lupus nephritis, with miR-146a being the most augmented (100-fold change, p<0.001). Among the exosomal miRNAs tested, only the miR-146a discriminates the presence of active lupus nephritis. In conclusion, urinary miRNAs are contained primarily in exosomes in systemic lupus erythematosus, and the main increment was found in the presence of active lupus nephritis. These findings underscore the attractiveness of exosomal miRNAs in urine, a non-invasive method, as potential renal disease markers.

miR-200c: a versatile watchdog in cancer progression, EMT, and drug resistance

“…For instance, levels of miR200c and seven other miRNAs in tumor-secreted exosomes were found to be similar to those in ovarian tumor cells confirming diagnostic potential of profiling circulating tumor exosomes [130]. Furthermore, exosomal secretion of miR-200c in urine has been observed in various chronic kidney diseases [133] and in systemic diseases such as lupus [137]. As a whole, miR-200c has a huge potential to be used as a biomarker of diagnosis, disease progression, and predicting treatment response.…”

Regulation of chronic inflammatory and immune processes by extracellular vesicles

“…The levels of these EVs in the sera correlated with disease severity and are thus a viable diagnostic tool for the assessment of these liver inflammatory diseases (100,101). Furthermore, the RNA profile of urine EVs from patients with SLE suggests that this approach could be used to determine the extent of kidney damage from lupus nephritis, which causes SLE-related morbidity and mortality (102,103).…”

Thu0234 the Transcription Factors Ikaros (Ikzf1) and Aiolos (Ikzf3) Are Expressed in the Salivary Glands of Sjögren’s Syndrome Patients With Lymphoid Aggregates and Modulate B Cell Activation in Vitro

“…Exosomal-derived urinary miRNAs can accurately reflect renal dysfunction and structural damage making them good biomarkers for diagnosis and prognosis [2]. In LN, urinary exosomal miR-29c expression levels have been identified as predictor of early fibrosis [3] and miR-146a upregulation as marker to discriminate active LN [4]. To the best of our knowledge, this is the first screening of miRNAs in urinary exosomes from LN patients to study their role as predictors of response to therapy.…”