Exosome-Based Approach to Diagnose Lupus in Patients with Renal Impairment

Scientific Research Group and Renal cardiometabolic risk, in collaboration with the Unit of Genotyping and Genetic Diagnosis INCLIVA Research Institute and the Internal Medicine Unit of the Clinical Hospital, demonstrating the presence of extracellular vesicles in the urine of patients diagnosed with lupus.

The work was published in late September in the international journal PLoS One, along with another in Disease Markers, reviews, explaining the role of extracellular vesicles have in the pathology of lupus.

Lupus is a chronic autoimmune disease that can affect almost every organ of the body, joints, kidneys, heart, skin, blood vessels, lungs, etc., whose cause is unknown.

It is a very heterogeneous disease with symptoms, with symptoms that come and go in outbreaks, hence the complexity of diagnosis. To date, lupus has no single diagnostic technique that has become final. The diagnosis is mainly based on symptoms, clinical findings and complementary laboratory tests.

It is a disease that most often affects women, at a time of life in which she is fertile, between 20 and 40 years. According to the Spanish Society of Rheumatology in Spain currently Lupus affects about 40,000 people.

Coordinated by the Scientific Director of the Institute, Josep Redon, the project has focused on lupus patients with renal impairment, lupus nephritis, as in the kidney microRNAs play an indispensable role in regulating the mechanisms of development and maintenance renal function.

Dr. Raquel Cortes, Postdoctoral Researcher, explains that “the research focused on techniques obtained by ultracentrifugation, exosomes (extracellular vesicles smaller) and quantify the levels of several microRNAs associated with lupus.”

“Our results show that patients with active lupus and kidney disease have higher levels of miRNAs in urine, compared with patients in the control group where the alterations derived from lupus are not present. A higher degree of kidney involvement by this pathology, the greater the presence mainly of miR-146a in exosomes, which does not occur in the complete urine “reveals. “We use a technique that increases sensitivity to quantifying changes in the levels of miRNAs, and that allows us to be more accurate when it comes to being able to diagnose or predict the degree of activation of kidney damage or predict the response of different treatments” .

Dr. Cortés explains that “extracellular vesicles, among which are exosomes are a new intercellular messenger communicating cells may be a great distance. These vesicles contain proteins, nucleic acids (DNA, RNA, mRNA and miRNAs) and lipids, and can be manipulated in order to incorporate a certain compound, that is incorporated by the target cell receptor. Understanding why and how they communicate with the correct target cell would be a revolution, “he concludes.

Progresses to “ultracentrifugation technique employed is not a method that can be used massively for diagnosis, thus different commercial houses are developing protocols for faster and simpler production of the vesicles, because of its great importance in various pathophysiologic diseases”.

exosome rna

Role of extracellular vesicles in inflammation. Extracellular vesicles (EVs) from mature dendritic cells (DC) provide antigen to T cells and promote a proinflammatory response, mediated by host factors present within exosomes and apoptotic bodies (TNF, HMGB1, etc.). Autoantigens in EVs are recognized by autoantibodies and form immune complexes. Platelet-derived microvesicles (PMVs) activate DC and carry IL-1β. EVs in target cell can be involved in antigen presentation and the transfer of major histocompatibility complex (MHC) molecules and antigens, participating in immune regulation. Finally, EVs activate or transfer surface receptors and deliver various RNA species (including mRNA and small RNAs) to target cells. DC: dendritic cell, EVs: extracellular vesicles, MHC: major histocompatibility complex, and PMVs: platelet-derived microvesicles.

Source: INCLIVA

Perez-Hernandez J, Forner MJ, Pinto C, Chaves FJ, Cortes R, Redon J (2015) Increased Urinary Exosomal MicroRNAs in Patients with Systemic Lupus Erythematosus. PLoS ONE 10(9): e0138618. [article]
Perez-Hernandez J, Cortes R. (2015) Extracellular Vesicles as Biomarkers of Systemic Lupus Erythematosus. Dis Markers 2015:613536. [article]

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