Long noncoding RNAs (lncRNAs), including large intergenic noncoding RNAs (lincRNAs), are mRNA-like molecules with no functional open reading frames that can regulate immunological processes. Wu et al. now show that linc0949 expression is inversely associated with disease activity and organ damage in patients with systemic lupus erythematosus (SLE).

The expression of four lincRNAs (linc0949, linc0597, linc1992 and linc3995) was measured by real time quantitative PCR in peripheral blood mononuclear cells (PBMCs) from 102 patients with SLE, 54 patients with rheumatoid arthritis (RA) and 76 healthy donors. Patients with SLE had lower expression of linc0949 and linc0597 when compared with patients with RA or controls, and expression of linc0949, but not of linc0597, was lower in patients with SLE who had a mild flare (P = 0.0032) or a moderate-to-severe flare (P = 0.0004) when compared with patients with SLE with no flare as assessed by SLE disease activity index 2000 (SLEDAI-2K) scoring. The expression of linc0949 was also inversely correlated with SLEDAI-2K score (r = −0.329, P = 0.0007) and positively correlated with complement C3 levels (r = 0.348, P = 0.0003).

Credit: NPG

In further support of an important role for linc0949 in SLE, expression of this lincRNA was also reduced in patients with increased organ damage as assessed by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (score >2 versus no damage, P = 0.0009), and in patients with lupus nephritis compared with those with no renal involvement (P = 0.0014). Additionally, PBMCs from patients with SLE were unable to regulate linc0949 and linc0597 expression after Pam3CSK4 activation, suggesting a cell-intrinsic immune defect in these patients.

“Defining disease relevant lncRNAs among patients with SLE may help us establish novel biomarkers and potential therapeutic targets,” explains Nan Shen, the corresponding author of the study. “It would be important for us to further dissect why lncRNA expression is aberrant in patients with SLE and what are the underlying biological mechanisms in autoimmune disease,” he adds. Further research will be needed to determine whether these lncRNAs could be considered disease susceptibility markers and to understand how these lncRNAs are linked to dysregulation of the immune system.