High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers of Kidney Damage in Patients with Systemic Lupus Erythematosus.
Renal involvement is one of the most severe manifestations of systemic lupus erythematosus (SLE). Renal biopsy is the gold standard when it comes to knowing whether a patient has lupus nephritis, and the degree of renal disease present. However, the biopsy has various complications, bleeding being the most common. Therefore, the development of alternative, non-invasive diagnostic tests for kidney disease in patients with SLE is a priority. Micro RNAs (miRNAs) are differentially expressed in various tissues, and changes in their expression have been associated with several pathological processes. The aim of this study was to identify changes in the abundance of miRNAs in plasma samples from patients with lupus nephritis that could potentially allow the diagnosis of renal damage in SLE patients. This is an observational case-control cross-sectional study, in which we characterized the differential abundance profiles of miRNAs among patients with different degrees of lupus compared with SLE patients without renal involvement and healthy control individuals. We found 89 miRNAs with changes in their abundance between lupus nephritis patients and healthy controls, and 17 miRNAs that showed significant variations between SLE patients with or without renal involvement. Validation for qPCR of a group of miRNAs on additional samples from lupus patients with or without nephritis, and from healthy individuals, showed that five miRNAs presented an average detection sensitivity of 97%, a specificity of 70.3%, a positive predictive value of 82.5%, a negative predictive value of 96% and a diagnosis efficiency of 87.9%. These results strongly suggest that miR-221-5p, miR-380-3p, miR-556-5p, miR-758-3p and miR-3074-3p are potential diagnostic biomarkers of lupus nephritis in patients with SLE. The observed differential pattern of miRNA abundance may have functional implications in the pathophysiology of SLE renal damage.
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.
Elkin
http://orcid.org/0000-0001-7567-6409
E
Navarro-Quiroz
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.
Lisandro
L
Pacheco-Lugo
Infectious Diseases Department, J. Craig Venter Institute, Rockville, Maryland, United States of America.
Hernan
H
Lorenzi
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.
Yirys
Y
Díaz-Olmos
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.
Lisneth
L
Almendrales
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.
Edwin
E
Rico
Grupo de Genética, Universidad Cooperativa de Colombia, Santa Marta, Colombia.
Roberto
R
Navarro
Monómeros, Barranquilla, Colombia.
Pierine
P
España-Puccini
Unidad de Reumatología, Universidad Nacional de Colombia, Bogotá, Colombia.
Antonio
A
Iglesias
Grupo de Investigación en Inmunología y Biología Molecular, Universidad del Norte, Barranquilla, Colombia.
Eduardo
E
Egea
Grupo de Nefrología, Universidad Simón Bolívar, Barranquilla, Colombia.|Clínica de la Costa, Barranquilla, Colombia.
Gustavo
G
Aroca
D000328:Adult; D015415:Biomarkers / Q000097:blood*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics*; D008181:Lupus Nephritis / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D025341:Principal Component Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
D015415:Biomarkers; D035683:MicroRNAs; C525709:MIR221, human; C000621110:MIRN3074 microRNA, human; C553224:MIRN380 microRNA, human; C000611992:MIRN556 microRNA, human; C569441:MIRN758 microRNA, human