Gut microbiota regulation of T lymphocyte subsets during systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by disturbance of pro-inflammatory and anti-inflammatory lymphocytes. Growing evidence shown that gut microbiota participated in the occurrence and development of SLE by affecting the differentiation and function of intestinal immune cells. The purpose of this study was to investigate the changes of gut microbiota in SLE and judge its associations with peripheral T lymphocytes. METHODS: A total of 19 SLE patients and 16 HCs were enrolled in this study. Flow cytometry was used to detect the number of peripheral T lymphocyte subsets, and 16 s rRNA was used to detect the relative abundance of gut microbiota. Analyzed the correlation between gut microbiota with SLEDAI, ESR, ds-DNA and complement. SPSS26.0 software was used to analyze the experimental data. Mann-Whitney U test was applied to compare T lymphocyte subsets. Spearman analysis was used for calculating correlation. RESULTS: Compared with HCs, the proportions of Tregs (P = 0.001), Tfh cells (P = 0.018) and Naïve CD4 + T cells (P = 0.004) significantly decreased in SLE patients, and proportions of Th17 cells (P = 0.020) and γδT cells (P = 0.018) increased in SLE. The diversity of SLE patients were significantly decreased. Addition, there were 11 species of flora were discovered to be distinctly different in SLE group (P < 0.05). In the correlation analysis of SLE, Tregs were positively correlated with Ruminococcus2 (P = 0.042), Th17 cells were positively correlated with Megamonas (P = 0.009), γδT cells were positively correlated with Megamonas (P = 0.003) and Streptococcus (P = 0.004), Tfh cells were positively correlated with Bacteroides (P = 0.040), and Th1 cells were negatively correlated with Bifidobacterium (P = 0.005). As for clinical indicators, the level of Tregs was negatively correlated with ESR (P = 0.031), but not with C3 and C4, and the remaining cells were not significantly correlated with ESR, C3 and C4. CONCLUSION: Gut microbiota and T lymphocyte subsets of SLE changed and related to each other, which may break the immune balance and affect the occurrence and development of SLE. Therefore, it is necessary to pay attention to the changes of gut microbiota and provide new ideas for the treatment of SLE.

Study on the expression changes of lncRNA in patients with systemic lupus erythematosus and its correlation with Treg cells.

OBJECTIVES: We initially explored the link between the differentially expressed long non-coding RNAs (lncRNAs) and the number of regulatory T (Treg) cells by detecting the lncRNA expression profiles in patients with systemic lupus erythematosus (SLE), then analyzed the correlation between Treg-related lncRNAs and the clinical features of SLE patients, predicting the mechanism by which lncRNAs regulate the differentiation and development of Treg cells, and provided new ideas for the treatment of SLE. METHODS: Peripheral blood of 9 active SLE patients were collected and mononuclear cells (PBMCs) were extracted; the lncRNA expression profiles of PBMCs were analyzed by whole transcriptome sequencing. Nine healthy people were used as controls to screen the differentially expressed lncRNAs, to analyze the correlation between lncRNAs and Treg cell number. Pearson test was used to analyze the correlation between lncRNAs and the number of Treg cell, and the correlation between Treg-associated lncRNA and SLEDAI score, ESR, C3, and C4 in SLE patients. The targeted genes of Treg-associated lncRNAs were predicted with miRcode and Targetscan databases and coexpression network. RESULTS: There were 240 differentially expressed lncRNAs in SLE patients compared with healthy controls, including 134 highly expressed lncRNAs (p < 0.05) and 106 lowly expressed lncRNAs (p < 0.05). The expression of ANKRD44-AS1 (r = 0.7417, p = 0.0222), LINC00200 (r = 0.6960, p = 0.0373), AP001363.2 (r = 0.7766, p = 0.0138), and LINC02824 (r = 0.7893, p = 0.0114) were positively correlated with the number of Treg cell, and the expression of AP000640.1 (r = - 0.7225, p = 0.0279), AC124248.1 (r = - 0.7653, p = 0.0163), LINC00482 (r = - 0.8317, p = 0.0054), and MIR503HG (r = - 0.7617, p < 0.05) were negatively correlated with the number of Treg cell. Among these Treg-associated lncRNAs, the expression of LINC00482 (r = - 0.7348, p < 0.05) and MIR503 HG (r = - 0.7617, p < 0.05) were negatively correlated with C3. LINC00200, ANKRD44 - AS1, and AP000640.1 related to Treg cells regulate the expression of signal transducer and activator of transcription 5 (STAT5), phospholipase D1 (PLD1), homeodomain-only protein X (HOPX), and runt-related transcription factor 3 (RUNX3) through competitive binding of miRNA or trans-regulatory mechanism, thereby regulating the differentiation and development of Treg cell. CONCLUSIONS: The lncRNA expression profiles were changed in SLE patients, the differentially expressed lncRNAs were associated with abnormal number and function of Treg cells in SLE, and Treg-associated lncRNAs were associated with SLE-disease activity, which may affect the expression of STAT5, PLD1, HOPX, RUNX3 and regulate Treg cell function and participate in the pathogenesis and progression of SLE by competitively binding to miRNAs or trans-regulatory mechanism. Key points • Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and systems. lncRNAs may affect Treg cells function by regulating genes expression, which may be an important pathogenesis of SLE. • This study, taking SLE as an example, preliminarily analyzed the correlation between lncRNA and Treg cells in SLE patients, analyzed the correlation between Treg-related lncRNA and the clinical characteristics of SLE, and speculated that lncRNA could regulate the differentiation and development of Treg cells through competitive combination with miRNA or trans-regulatory mechanisms. • It is possible to target epigenetic therapy for SLE.

Clinical efficacy of plasma exchange in systemic lupus erythematosus during pregnancy.

OBJECTIVE: To investigate the clinical efficacy of plasma exchange (PE) with or without prednisone and hydroxychloroquine (HCQ) for the treatment of systemic lupus erythematosus (SLE) during pregnancy. METHODS: The clinical characteristics of 14 pregnant women with SLE admitted to our hospital were retrospectively analyzed, including 7 only treated with prednisone and HCQ (non-PE group) as well as 7 combined PE (PE group). The delivery situations of 14 patients were recorded. Data like erythrocyte sedimentation rate (ESR), urine protein, platelet count, and SLEDAI scores were compared between two groups before treatment and 3, 6, and 12 months after delivery. RESULTS: Three patients in the non-PE group ended in miscarriage while all patients in the PE group were delivered successfully. Eleven successfully delivered fetuses in the two groups were healthy, and the Apgar scores were over 8. The ESR of the PE group was significantly lower than that of the non-PE group at 6 and 12 months after delivery, while there was no statistical difference in ESR between the two groups before treatment and 3 months after delivery. The ESR and urine protein were significantly higher in the non-PE group at months 3, 6, and 12 postpartum. There was a significant decrease in disease activity postpartum in the PE group compared to predelivery disease activity. The change in platelet counts between the two groups significantly increased over time in the PE group, while SLEDAI scores decreased. CONCLUSIONS: The combination of PE and oral prednisone and HCQ is possibly a more effective treatment than oral prednisone and HCQ alone for patients with active SLE during pregnancy. This treatment option reduces pregnancy loss and promotes the patients' postpartum condition to a certain extent.