Biomarkers For Systemic Lupus Erythematosus Diagnosis Research Articles

Circulating miR-181a and miR-223 expression with the potential value of biomarkers for the diagnosis of systemic lupus erythematosus and predicting lupus nephritis.

MicroRNAs (miRNAs) contribute to the development and progression of systemic lupus erythematosus (SLE) by affecting a wide range of targeted genes and facilitating the development of lupus nephritis (LN). The present study aimed to analyze the serum expression of miR-181a and miR-223 in SLE patients and to assess whether they could serve as novel biomarkers for SLE diagnosis and to distinguish LN. The study included 70 control subjects and 116 patients with SLE (67 non-LN and 49 LN groups). Circulating miR-181a and miR-223 expression levels were analyzed among the Egyptian population using a real-time polymerase chain reaction. Up-regulation of miR-181a was detected among SLE patients compared to healthy controls and higher values were reported among the LN group compared to the non-LN group. Down-regulation of miR-223 was reported among SLE patients compared to controls and lower values were reported among the LN group compared to the non-LN group. The higher miR-181a expression and the lower miR-223 expression were associated with higher stages of LN. SLE disease activity index, proteinuria and serum creatinine were independently correlated with miR-181a and miR-223 among SLE patients by linear regression analysis. Receiver-operating characteristic curve analysis revealed that combined miR-181a and miR-223 expression increased the sensitivity and specificity for the diagnosis of SLE and further distinguished LN from non-LN patients. miR-181a and miR-223 could play a role in evaluating SLE disease progression and prognosis. Combined miR-181a and miR-223 expression analysis could serve as novel serum-based biomarkers in the diagnosis of SLE and predicting LN among Egyptians.

Identification of circular RNAs hsa_circ_0044235 and hsa_circ_0068367 as novel biomarkers for systemic lupus erythematosus

Circular RNAs (circRNAs) have emerged as novel biomarkers for disease diagnosis. However, the expression profiles and clinical significance of circRNAs in peripheral blood mononuclear cells (PBMCs) from systemic lupus erythematosus (SLE) remain unclear. In the present study, the expression profile of circRNAs in PBMCs from patients with SLE and healthy controls (HCs) was detected by using microarray analysis and verified by reverse transcription-quantitative polymerase chain reaction. A total of 1,603 circRNAs were identified to be significantly aberrantly expressed in PBMCs from patients with SLE. Validation assays in 30 SLE patients and 20 HCs demonstrated that the levels of hsa_circ_0044235 and hsa_circ_0068367 were significantly decreased in the patients with SLE. Receiver operating characteristic curve analysis suggested that hsa_circ_0044235 and hsa_circ_0068367 were significant for SLE diagnosis. Furthermore, the diagnostic potential of hsa_circ_0044235 and hsa_circ_0068367 for SLE was validated in an independent validation set with 45 patients with SLE, 38 HCs and 30 patients with rheumatoid arthritis. In addition, the level of hsa_circ_0044235 in the PBMCs from patients with SLE were identified to be significantly increased in new-onset SLE patients and in patients who were determined to be positive for anti-double-stranded DNA and anti-ribosomal protein P antibodies. Additionally, the level of a microRNA (miRNA) target of hsa_circ_0044235, hsa-miRNA-892a, was identified to be significantly increased in the PBMCs from patients with SLE. The present study suggested that the dysregulation of circRNAs may serve a role in SLE pathogenesis, and that the levels of hsa_circ_0044235 and hsa_circ_0068367 in PBMC have potential as biomarkers for SLE diagnosis.

Oxidative stress leads to reduction of plasmalogen serving as a novel biomarker for systemic lupus erythematosus

Oxidative stress is elevated in systemic lupus erythematosus (SLE) patients, and associated extensively with SLE pathogenesis. However, no common indicators of oxidative stress are yet in routine clinical use because of their instability, nonspecificity, and non-representation of all SLE symptoms. Moreover, the method for reproducible analysis of reactive oxygen species is still lacking. Lipids and their metabolites are essential components of biological systems, many of which serve as molecular targets of oxidative stress and play crucial roles in signaling, inflammation, and immune responses. Thus, determining the changed levels of lipids and their metabolites may serve the needs for SLE research. In the pilot study, shotgun lipidomics of sera from 30 SLE patients and 30 controls was performed and revealed a marked reduction of ethanolamine plasmalogen (pPE) species from 85.03±3.06 to 62.39±4.34 nmol/mL serum in controls and patients, respectively, accompanying significant increases in lysoPE (LPE) content (~46mol%) and 4-hydroxynonenal (an indictor of oxidative stress) in patients. Representative proinflammatory cytokines were also determined, revealing significant elevation of IL-6, IL-10, and TNF-α in SLE patients. Multivariate and multiple regression analyses showed for the first time that significant correlation among the SLE disease activity index, IL-10 levels, and pPE content exists, providing insights into SLE pathogenesis. The study also indicates that the changes of pPE (molecular targets of oxidative stress) and their peroxidation products may serve as novel biomarkers for diagnosis of SLE.