Abstract
Our understanding of circulating microRNAs (miRNAs) related to systemic lupus erythematosus (SLE) remains very limited. In this study, we screened SLE-specific miRNAs in plasma from 42 B cell-related miRNAs by using miRNA PCR Array. The selected miRNAs were first confirmed in plasma samples from 50 SLE patients, 16 rheumatoid arthritis (RA) patients, and 20 healthy donors using qRT-PCR. We then investigated the relationship between expressions of the selected miRNAs and SLE clinical indicators. As a result, 14 miRNAs (miR-103, miR-150, miR-20a, miR-223, miR-27a, miR-15b, miR-16, miR-181a, miR-19b, miR-22, miR-23a, miR-25, miR-92a, and miR-93) were significantly decreased in the plasma of SLE patients compared with healthy controls (P < 0.05) and could act as the diagnostic signature to distinguish SLE patients from healthy donors. Six miRNAs (miR-92a, miR-27a, miR-19b, miR-23a, miR-223, and miR-16) expressed in plasma were significantly lower in SLE patients than in RA patients (P < 0.05), revealing the potentially diagnostic signature to distinguish SLE patients from RA patients. Furthermore, the downregulated expression of miR-19b, miR-25, miR-93, and miR-15b was associated with SLE disease activity (P < 0.05) while miR-15b and miR-22 expressions were significantly lower in SLE patients with low estimate glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) (P < 0.05). The diagnostic potential of miR-15b for SLE disease activity and lupus nephritis (LN) with low eGFR was validated on an independent validation set with 69 SLE patients and a cross-validation set with 80 SLE patients. In summary, the signature of circulating miRNAs will provide novel biomarkers for the diagnosis of SLE and evaluation of disease activity and LN.
Highlights
Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease which affects multiple organs and systems and causes significant morbidity and mortality [1]
Additional 80 systemic lupus erythematosus (SLE) patients in cross-validation set were enrolled between March 2013 and September 2015 from the Department of 16 patients with rheumatoid arthritis (RA) using qRT-PCR. [3] The identified miRNAs related to the disease activity and lupus nephritis (LN) of SLE were re-validated on two independent SLE cohorts
According to our previous results of miRNAs profiling differentially expressed in B cells of SLE patients and combined with reported literature, 42 B cell-associated miRNAs (Tables S1–S4 in Supplementary Material) were selected to customize an miRNAs panel array for detecting plasma miRNAs associated with SLE
Summary
Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease which affects multiple organs and systems and causes significant morbidity and mortality [1]. Owing to its pathogenesis and the exact etiology that has not been completely elucidated, to discover novel biomarkers for early diagnosis of this disease and predicting the therapeutic outcome is very urgent, which enables clinicians to treat SLE patients with the most optimally biologic therapy as early as possible. Over the last decade, published studies have provided strong evidence for a connection between expression of dysregulated miRNAs and development of several systemic autoimmune diseases, including SLE, which gives us new insights into the pathogenesis of SLE and a new opportunity to find novel diagnostic or therapeutic targets [5,6,7,8,9,10,11,12,13]. Cell-free circulating miRNAs will be important biomarkers for SLE diagnosis
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