Identification of Long Noncoding RNAs lnc-DC in Plasma as a New Biomarker for Primary Sjögren’s Syndrome

Abstract

Objective. To evaluate the plasma levels of lnc-DC in primary Sjögren’s syndrome (pSS) patients and investigate the potential associations between lnc-DC and disease activity. Methods. In this study, we recruited 358 enrollments, including 127 pSS patients without immune thrombocytopenia (ITP), 22 pSS patients with ITP, 50 systemic lupus erythematosus (SLE) patients, and 50 patients with rheumatoid arthritis (RA) and 109 healthy individuals, from Xuzhou Central Hospital. The expression of anti-SSA and anti-SSB was detected by enzyme-linked immunosorbent assay (ELISA). Spearman rank correlation test was used to analyze the relationship between lnc-DC and pSS activity. pSS activity was measured by anti-SSA, anti-SSB antibody, erythrocyte sedimentation rate (ESR), and β2-microglobulin levels. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of plasma lnc-DC for pSS. Results. Compared with healthy controls, SLE and RA patients, the lnc-DC expression levels were significantly elevated in pSS patients ( P < 0.001 ), especially in pSS patients with ITP ( P < 0.001 ). As expected, we also found that the lnc-DC expression positively correlated with anti-SSA ( R 2 = 0.290 , P < 0.001 ), anti-SSB ( R 2 = 0.172 , P < 0.001 ), ESR level ( R 2 = 0.076 , P = 0.002 ), and β2-microglobulin level ( R 2 = 0.070 , P = 0.003 ) in pSS patients. ROC curves showed that plasma lnc-DC in pSS patients had an AUC 0.80 with a sensitivity of 0.75 and specificity of 0.85 at the optimum cutoff 1.06 in discriminating SLE and RA patients. In addition, the combination of lnc-DC and anti-SSA/SSB (AUC: 0.84, sensitivity: 0.79, specificity: 0.90) improved significantly the diagnostic ability of pSS patients from SLE and RA patients. In the efficacy monitoring study, levels of plasma lnc-DC were dramatically decreased after treatment ( P < 0.001 ). Conclusion. These findings highlight that plasma lnc-DC as a novel biomarker for the diagnosis of pSS and can be used to evaluate the therapeutic efficacy of pSS underwent interventional therapy.

One year in review 2021: Sjögren's syndrome

“…Finally, in the study of Chen et al, plasma levels of lnc-DC, a dendritic cell-specific LncRNA, was also found upregulated in SS compared to healthy and disease controls including lupus and rheumatoid arthritis patients. An interesting finding was that longitudinally assessed samples revealed a decrease in Inc-DC plasma levels after treatment (22). Adding to the complexity of epigenetic modifications in SS, an emerging player has been recently proposed, the Circular RNAs.…”

Long Intergenic Noncoding RNAs Affect Biological Pathways Underlying Autoimmune and Neurodegenerative Disorders

“…Chen et al analyzed the lnc-DC level in the plasma of 127 pSS patients without ITP (immune thrombocytopenia), 22 pSS patients with ITP, 50 patients with SLE, 50 patients with RA, and 109 healthy individuals and reported that the lnc-DC level was significantly elevated in pSS patients, especially in pSS patients with ITP. The lnc-DC expression level was positively correlated with some clinical pSS characteristics, including the β 2 -microglobulin, anti-SSA and anti-SSB antibody levels, and the erythrocyte sedimentation rate [ 58 ]. The researchers suggested that through STAT3 regulation, lnc-DCs can induce Th17 cell differentiation and, therefore, the secretion of a variety of cytokines is involved in the occurrence and development of pSS [ 12 , 58 ].…”

“…The lnc-DC expression level was positively correlated with some clinical pSS characteristics, including the β 2 -microglobulin, anti-SSA and anti-SSB antibody levels, and the erythrocyte sedimentation rate [ 58 ]. The researchers suggested that through STAT3 regulation, lnc-DCs can induce Th17 cell differentiation and, therefore, the secretion of a variety of cytokines is involved in the occurrence and development of pSS [ 12 , 58 ]. Moreover, scientists found that the combined analysis of lnc-DC and anti-SSA/SSB antibody levels significantly improved the diagnostic ability and could be used to distinguish pSS patients from SLE and RA patients [ 58 ].…”

“…The researchers suggested that through STAT3 regulation, lnc-DCs can induce Th17 cell differentiation and, therefore, the secretion of a variety of cytokines is involved in the occurrence and development of pSS [ 12 , 58 ]. Moreover, scientists found that the combined analysis of lnc-DC and anti-SSA/SSB antibody levels significantly improved the diagnostic ability and could be used to distinguish pSS patients from SLE and RA patients [ 58 ].…”

Interferon-alpha regulates expression of lncRNA MALAT1 and interferon-stimulated genes, as well as chemokine production, in primary Sjögren's syndrome

“…In pSS, IFN-α and their respective type I interferon-stimulated genes (ISG) contribute to distinct phenotypes, as several ISGs are associated with the presence of anti-SSA/ Ro or anti-SSB/La antibodies (10)(11)(12). Similarly, lncRNA expression profiles in labial salivary glands and plasma are increased in pSS patients compared to healthy donors (13,14). Consequently, it is plausible that different lncRNAmediated molecular mechanisms may be involved in the pathogenesis of pSS.…”