Differences in the expression of long noncoding RNAs in peripheral blood mononuclear cells indicate potential biomarkers for rheumatoid arthritis.

Long noncoding RNAs (lncRNAs) play an increasingly important role in various autoimmune diseases. We aimed to characterize the expression profiles of lncRNAs in peripheral blood mononuclear cells (PBMCs) from RA patients and to assess the potential of these lncRNAs as RA biomarkers. Whole-transcriptome sequencing was used to establish a lncRNA expression profile. A total of 155 RA patients, 145 healthy controls, 59 systemic lupus erythematosus (SLE) patients and 59 primary Sjögren's syndrome (pSS) patients were recruited for this study. Four candidate lncRNAs (linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7) were validated via qRT-PCR in independent samples, and their expression, association with RA clinical features and value as RA biomarkers were evaluated. Linc00152 and lnc-ADM-1 exhibited upregulated expression (p = 0.001, p = 0.014, respectively), while ITSN1-2 and lnc-FTH1-7 exhibited downregulated expression (both p < 0.001, respectively) in RA patients compared to controls. Lnc-ADM-1 and lnc-FTH1-7 expression correlated positively with the C4 level (p = 0.016 and p = 0.012, respectively). ITSN1-2 levels were negatively associated with CRP levels (p = 0.024). Linc00152, lnc-ADM-1, ITSN1-2, and lnc-FTH1-7 showed potential as RA biomarkers, with the four-lncRNA panel distinguishing RA patients from controls, SLE patients, or pSS patients (AUC = 0.886, 0.746, and 0.749, respectively). The altered expression of linc00152, lnc-ADM-1, ITSN1-2 and lnc-FTH1-7 in RA patients suggested that these genes may serve as potential biomarkers for RA and could be involved in its pathogenesis.

Li HM ，Wang LJ ，Wang YP ，Li XM ，Pan HF ... -  《-》

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

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. 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 β 2-microglobulin levels. The receiver operating characteristic (ROC) curve was used to determine the diagnostic performance of plasma lnc-DC for pSS. 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 β 2-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). 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.

Chen Y ，Chen Y ，Zu B ，Liu J ，Sun L ，Ding C ，Wang D ，Cheng X ，Yang D ，Niu G ... -  《-》

Differential Plasma Expression Profiles of Long Non-Coding RNAs Reveal Potential Biomarkers for Systemic Lupus Erythematosus.

Wu GC ，Hu Y ，Guan SY ，Ye DQ ，Pan HF ... -  《Biomolecules》

A novel long noncoding RNA ENST00000597482 serves as a potential biomarker for disease activity and diagnosis of systemic lupus erythematosus.

Wang C ，Yuan S ，Zeng Y ，Li W ，Ye J ，Li F ，He Z ，Chen Y ，Lin X ，Liang L ，Xu H ，Cai X ... -  《-》

Rheumatoid arthritis, systemic lupus erythematosus and primary Sjögren's syndrome shared megakaryocyte expansion in peripheral blood.

Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) share many clinical manifestations and serological features. The aim of this study was to identify the common transcriptional profiling and composition of immune cells in peripheral blood in these autoimmune diseases (ADs). We analysed bulk RNA-seq data for enrichment of biological processes, transcription factors (TFs) and deconvolution-based immune cell types from peripheral blood mononuclear cells (PBMCs) in 119 treatment-naive patients (41 RA, 38 pSS, 28 SLE and 12 polyautoimmunity) and 20 healthy controls. The single-cell RNA-seq (scRNA-seq) and flow cytometry had been performed to further define the immune cell subsets on PBMCs. Similar transcriptional profiles and common gene expression signatures associated with nucleosome assembly and haemostasis were identified across RA, SLE, pSS and polyautoimmunity. Distinct TF ensembles and gene regulatory network were mainly enriched in haematopoiesis. The upregulated cell-lineage-specific TFs PBX1, GATA1, TAL1 and GFI1B demonstrated a strong gene expression signature of megakaryocyte (MK) expansion. Gene expression-based cell type enrichment revealed elevated MK composition, specifically, CD41b+CD42b+ and CD41b+CD61+ MKs were expanded, further confirmed by flow cytometry in these ADs. In scRNA-seq data, MKs were defined by TFs PBX1/GATA1/TAL1 and pre-T-cell antigen receptor gene, PTCRA. Cellular heterogeneity and a distinct immune subpopulation with functional enrichment of antigen presentation were observed in MKs. The identification of MK expansion provided new insights into the peripheral immune cell atlas across RA, SLE, pSS and polyautoimmunity. Aberrant regulation of the MK expansion might contribute to the pathogenesis of these ADs.

Wang Y ，Xie X ，Zhang C ，Su M ，Gao S ，Wang J ，Lu C ，Lin Q ，Lin J ，Matucci-Cerinic M ，Furst DE ，Zhang G ... -  《-》