Systemic lupus erythematosus (SLE), often considered the prototype of autoimmune diseases, is characterized by over-activation of the autoimmune system with abnormal functions of innate and adaptive immune cells and the production of a large number of autoantibodies against nuclear components. Given the highly complex and heterogeneous nature of SLE, the pathogenesis of this disease remains incompletely understood and is presumed to involve both genetic and environmental factors. Currently, disturbance of the gut microbiota has emerged as a novel player involved in the pathogenesis of SLE. With in-depth research, the understanding of the intestinal bacteria-host interaction in SLE is much more comprehensive. Recent years have also seen an increase in metabolomics studies in SLE with the attempt to identify potential biomarkers for diagnosis or disease activity monitoring. An intricate relationship between gut microbiome changes and metabolic alterations could help explain the mechanisms by which gut bacteria play roles in the pathogenesis of SLE. Here, we review the role of microbiota dysbiosis in the aetiology of SLE and how intestinal microbiota interact with the host metabolism axis. A proposed treatment strategy for SLE based on gut microbiome (GM) regulation is also discussed in this review. Increasing our understanding of gut microbiota and their function in lupus will provide us with novel opportunities to develop effective and precise diagnostic strategies and to explore potential microbiota-based treatments for patients with lupus.
Oral microbial dysbiosis is known to increase susceptibility of an individual to develop rheumatoid arthritis (RA). Individuals at-risk of RA may undergo different phases of disease progression. In this study, we aim to investigate whether and whereby the oral microbiome communities alter prior to symptoms of RA. Seventy-nine saliva samples were collected from 29 high-risk individuals, who were positive for anti-citrullinated protein antibodies (ACPA) and have no clinical arthritis, 27 RA patients and 23 healthy controls (HCs). The salivary microbiome was examined using 16S ribosomal RNA gene sequencing. Alpha and beta diversity analysis and the linear discriminant analysis were applied to examine the bacterial diversity, community structure and discriminatory taxa between three groups, respectively. The correlation between salivary bacteria and autoantibodies were analyzed. In the "pre-clinical" stages, salivary microbial diversity was significantly reduced comparing to RA patients and HCs. In contrast to HCs, like RA patients, individuals at high-risk for RA showed a reduction in the abundance of genus Defluviitaleaceae_UCG-011 and the species Neisseria oralis, but an expansion of Prevotella_6. Unexpectedly, the relative abundance of Porphyromonas gingivalis, reported as opportunistic pathogens for RA development, was significantly decreased in high-risk individuals. Additionally, we identified four genera in the saliva from high-risk individuals positively correlated with serum ACPA titers, and the other two genera inversely displayed. In summary, we observed a characteristic compositional change of salivary microbes in individuals at high-risk for RA, suggesting that oral microbiota dysbiosis occurs in the "pre-clinical" stage of RA and are correlated with systemic autoimmune features.
Rheumatoid arthritis (RA) is an autoimmune disorder with dysregulation of long noncoding RNAs (lncRNAs) possibly involved. This study aimed to inquire into the roles of lncRNA OIP5-AS1 in RA progression. A rat model of RA was induced. Overexpression of OIP5-AS1 was introduced in the model rats, and the changes in paw swelling, RA severity and the inflammatory factors interleukin (IL)-1β, IL-10, IL-6 and tumour necrosis factor α were measured. Fibroblast-like synoviocytes (FLSs) from RA patients were collected for in vitro experiments. A gain-and loss-of function study of OIP5-AS1, miR-448 and paraoxonase 1 (PON1) was performed to explore their roles in RA-FLS growth, apoptosis and inflammation. A toll-like receptor 3 (TLR3)-specific agonist, polyinosine-polycytidylic acid, or a nuclear factor κB (NF-κB)-specific antagonist, QNZ, was administrated in RA-FLSs. Consequently, overexpression of OIP5-AS1 reduced the symptom severity and the levels of inflammatory factors in RA rats. OIP5-AS1 could bind to miR-448 to up-regulate PON1 expression. Further overexpression of miR-448 reversed the effects of OIP5-AS1, while overexpression of PON1 inhibited RA-FLS growth and inflammation. In addition, TLR3 activation promoted RA progression. To conclude, this study evidenced that lncRNA OIP5-AS1 may mitigate RA progression through the miR-448-PON1 axis and through the inactivation of the TLR3-NF-κB signalling pathway. K E Y W O R D S long non-coding RNA OIP5-AS1, microRNA-448, paraoxonase 1, rheumatoid arthritis, TLR3/NF-κB signalling pathway 1 INTRODUCTION Rheumatoid arthritis (RA) is a common chronic autoimmune disorder that features severe synovial proliferation, inflammation, rheumatoid pannus formation and autoantibody production (Hoxha, 2018). This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
TL1A is a member of the TNF superfamily. It performs significantly in the pathogenesis of rheumatic and autoimmune diseases partly through regulating the Th17 pathway. The clinical implication of circulating TL1A in patients with systemic sclerosis (SSc) remains unclear, and correlation between TL1A and Th17-related cytokines in the pathogenesis of SSc needs to be discussed. We measured serum levels of TL1A and Th17-related cytokines by ELISA in 47 patients with SSc, 56 patients with SLE, and 53 healthy subjects, and investigated association of these cytokines with clinical manifestations and laboratory variables. TL1A in relation to Th17-related cytokines were examined. In addition, the transcript level of TL1A in peripheral blood mononuclear cells (PBMCs) was determined by real-time reverse transcription polymerase chain reaction (real-time PCR). Serum TL1A levels were higher in patients with SSc than in healthy controls (P = 0.001), but were lower compared with SLE patients (P = 0.004). Diffuse cutaneous SSc or limited cutaneous SSc patients reported elevated expression of TL1A than those in healthy controls (P = 0.002, P = 0.007). Patients with active disease showed significantly higher expression of TL1A when compared with less active disease (P = 0.014). SSc patients with arthritis, elevated IgG titer, ESR >30 mm/h, and CRP >5 mg/l displayed elevated expression of TL1A, respectively. Serum levels of IL-17 and IL-21 were increased in SSc patients compared with healthy controls and positively related to TL1A levels (r = 0.373, P = 0.010; r = 0.370, P = 0.011, respectively). Moreover, TL1A mRNA expression in PBMCs was significantly higher in patients with SSc compared with healthy controls (P < 0.001). TL1A may play a role in the development of SSc.
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