MicroRNAs (miRNAs) are noncoding RNA molecules of 21—24 nt that regulate the expression of target genes in a post-transcriptional manner. Evidence indicates that miRNAs play essential roles in embryogenesis, cell differentiation and pathogenesis of human diseases. This study describes a comparison between the miRNA profile of the systemic lupus erythematosus (SLE) patients and the controls to develop further understanding of the pathogenesis of SLE. Peripheral blood mononuclear cells were isolated from blood samples of 23 SLE patients, 10 idiopathic thrombocytopenic purpura patients and 10 healthy controls. The miRNA microarray chip analysis identified 16 miRNAs differentially expressed in SLE. The chip results were confirmed by northern blot analysis. This work indicates that miRNAs are potential diagnosis biomarkers and probable factors involved in the pathogenesis of SLE. Lupus (2007) 16, 936—946.

Objective: Primary Sjögren’s syndrome (pSS) is a systemic autoimmune disease, and its pathogenetic mechanism is far from being understood. In this study, we aimed to explore the cellular and molecular mechanisms that lead to pathogenesis of this disease.Methods: We applied single-cell RNA sequencing (scRNA-seq) to 57,288 peripheral blood mononuclear cells (PBMCs) from five patients with pSS and five healthy controls. The immune cell subsets and susceptibility genes involved in the pathogenesis of pSS were analyzed. Flow cytometry was preformed to verify the result of scRNA-seq.Results: We identified two subpopulations significantly expand in pSS patients. The one highly expressing cytotoxicity genes is named as CD4⁺ CTLs cytotoxic T lymphocyte, and another highly expressing T cell receptor (TCR) variable gene is named as CD4⁺ TRAV13-2+ T cell. Flow cytometry results showed the percentages of CD4⁺ CTLs, which were profiled with CD4⁺ and GZMB⁺ staining; the total T cells of 10 patients with pSS were significantly higher than those of 10 healthy controls (P= 0.008). The expression level of IL-1β in macrophages, TCL1A in B cells, as well as interferon (IFN) response genes in most cell subsets was upregulated in the patients with pSS. Susceptibility genes including HLA-DRB5, CTLA4, and AQP3 were highly expressed in patients with pSS.Conclusions: Our data revealed disease-specific immune cell subsets and provided some potential new targets of pSS. Specific expansion of CD4⁺ CTLs may be involved in the pathogenesis of pSS, which might give valuable insights for therapeutic interventions of pSS.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by multi-system involvement, diverse clinical presentation, and alterations in circulating metabolites. In this study, a ¹H NMR spectroscopy-based metabolomics approach was applied to establish a human SLE serum metabolic profile. Serum samples were obtained from patients with SLE ( n = 64), patients with rheumatoid arthritis (RA) ( n = 30) and healthy controls ( n = 35). The NOESYPR1D spectrum combined with multi-variate pattern recognition analysis was used to cluster the groups and establish a disease-specific metabolites phenotype. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were capable of distinguishing SLE or RA patients from healthy subjects. The OPLS-DA model was able to predict diagnosis of SLE with a sensitivity rate of 60.9% and a specificity rate of 97.1%. For diagnosing RA, the model has much higher sensitivity (96.7%) and specificity (91.4%). The SLE serum samples were characterized by reduced concentrations of valine, tyrosine, phenylalanine, lysine, isoleucine, histidine, glutamine, alanine, citrate, creatinine, creatine, pyruvate, high-density lipoprotein, cholesterol, glycerol, formate and increased concentrations of N-acetyl glycoprotein, very low-density lipoprotein and low-density lipoprotein in comparison with the control population. Theresults not only indicated that serum NMR-based metabolomic methods had sufficient sensitivity and specificity to distinguish SLE and RA from healthy controls, but also have the potential to be developed into a clinically useful diagnostic tool, and could also contribute to a further understanding of disease mechanisms.