Tumor necrosis factor-α, its related immunoregulatory long non-coding RNA (THRIL) and micro-RNA 145 as potential biomarkers in lupus nephritis patients

Abstract

Aim of the work

To explore the differential expression of tumor necrosis factor-α (TNF-α), its related immunoregulatory long non-coding RNA (THRIL), and microRNA145 (MIR145) in systemic lupus erythematosus (SLE) patients and their diagnostic utility in lupus nephritis (LN).

Patients and methods

The study included 60 SLE patients; 30 with LN, 30 without LN (NN), and 30 matched controls. SLE disease activity index was assessed. Serum TNF-α level was determined by enzyme linked immunosorbent assay. Serum fold change (FC) in expression of THRIL and MIR145 were assayed by real time polymerase chain reaction.

Results

The patients mean age was 32.6 ± 6.8 years and were 52 females and 8 males (F:M 6.5:1). Serum TNF-α level was significantly higher in SLE patients (108.6 ± 47.8 pg/ml) compared to control (39.6 ± 3.7 pg/ml) (p < 0.001). THRIL expression was upregulated (8.3 ± 6.9 vs. 1.02 ± 0.06 FC, p < 0.001) and MIR145 downregulated (0.39 ± 0.36 vs. 0.92 ± 0.94 FC, p < 0.001) in SLE patients versus controls. THRIL correlated with disease activity (r = 0.27, p = 0.035) and MIR145 with C3 (r = −0.32, p = 0.04) and C4 (r = −0.36, p = 0.016) levels in SLE patients. In LN patients, TNF-α and THRIL were increased while MIR145 downregulated (p < 0.001 each) and proteinuria significantly correlated with TNF-α (r = −0.4,p = 0.028), THRIL (r = 0.48, p = 0.007) and MIR145 (-0.42, p = 0.02). In NN patients, TNF-α and THRIL (p < 0.001 both) were increased while MIR145 downregulated (p = 0.023). TNF-α (cutoff ≥ 122.5 pg/ml, AUC 0.67, p = 0.003), and MIR145 (cutoff ≤ 0.22 FC, AUC 0.71, p = 0.026) discriminated LN from NN. The combination of TNF-α and MIR145 discriminated better than either alone (AUC 0.75, p = 0.002).

Conclusion

TNF-α and MIR145 are potential biomarkers of LN in SLE.