The incidence of systemic lupus erythematosus (SLE) is known to be affected by sex hormone. Patients with Klinefelter's syndrome were reported to have abnormal sex hormonal metabolism and their chronic estrogenic stimulation seems to affect the pathogenesis of SLE. Therefore, association of SLE and Klinefelter's syndrome has been considered as a clue of the effect of sex hormone on SLE. We report the first case of Klinefelter's syndrome in a patient with SLE in Korea and discuss the association of SLE with Klinefelter's syndrome.
Estrogens ; Humans ; Incidence ; Klinefelter Syndrome* ; Korea ; Lupus Erythematosus, Systemic* ; Metabolism

This review attempts to define the relationship between IL-15 and autoimmune disease (AID) from IL-15's tissue distribution, expression regulation and biologic function. Meanwhile, five IL-15 dysregulation-related AIDs and four IL-15/IL-15R-targeted AID therapies are described.
Animals ; Autoimmune Diseases ; metabolism ; Humans ; Interleukin-15 ; metabolism ; Lupus Erythematosus, Systemic ; metabolism ; Multiple Sclerosis ; metabolism

This study examined the gene expression patterns of peripheral blood mononuclear cells (PBMCs) in patients with systemic lupus erythematosus (SLE) by using serial analysis of gene expression (SAGE) technology. Following the construction of serial analysis of gene expression (SAGE) library of PBMCs collected from 3 cases of familial SLE patients, a large scale of tag sequencing was performed. The data extracted from sequencing files was analyzed with SAGE 2000 V 4.5 software. The top 30 expressed genes of SLE patients were uploaded to http://david.niaid.nih.gov/david/ease.htm and the functional classification of genes was obtained. The differences among those expressed gene were analyzed by Chi-square tests. The results showed that a total of 1286 unique SAGE tags were identified from 1814 individual SAGE tags. Among the 1286 unique tags, 86.8% had single copy, and only 0.2% tags had more than 20 copies. And 68.4% of the tags matched known expressed sequences, 41.1% of which matched more than one known expressed sequence. About 31.6% of the tags had no match and could represent potentially novel genes. Approximately one third of the top 30 genes were ribosomal protein, and the rest were genes related to metabolism or with unknown functions. Eight tags were found to express differentially in SAGE library of SLE patients. This study draws a profile of gene expression patterns of PBMCs in patients with SLE. Comparison of SAGE database from PBMCs between normal individuals and SLE patients will help us to better understand the pathogenesis of SLE.
Expressed Sequence Tags ; Gene Expression Profiling/*methods ; Leukocytes, Mononuclear/*metabolism ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/*genetics ; Sequence Tagged Sites ; Transcription, Genetic

Objective To identify the relationship between nephritis activity, autophagy and inflammation in patients with SLE. Methods Western blot analysis was used to detect the expression of microtubule-associated protein 1 light chain 3 (LC3) and P62 in peripheral blood mononuclear cells (PBMCs) of SLE patients with lupus nephritis and non-lupus nephritis patients. Tumor necrosis factor α (TNF-α) and interferon γ (IFN-γ) in the serum of SLE patients were determined by ELISA. The correlation between LC3II/LC3I ratio and SLE disease activity score (SLEDAI), urinary protein, TNF-α and IFN-γ levels was analyzed by Pearson method. Results The expression of LC3 was increased and P62 was decreased in SLE patients. TNF-α and IFN-γ were increased in the serum of SLE patients. LC3II/LC3I ratio was positively correlated with SLEDAI (r=0.4560), 24 hour urine protein (r=0.3753), IFN-γ (r=0.5685), but had no correlation with TNF-α (r=0.04 683). Conclusion Autophagy is found in PBMCs of SLE, and the autophagy is correlated with renal damage and inflammation in patients with lupus nephritis.
Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Leukocytes, Mononuclear/metabolism* ; Autophagy-Related Proteins/metabolism* ; Lupus Nephritis/urine* ; Kidney ; Interferon-gamma/metabolism* ; Inflammation/metabolism* ; Lupus Erythematosus, Systemic/metabolism*

OBJECTIVETo explore the expression pattern of microRNAs in the peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), with an attempt to identify the role of microRNA in the pathogenesis of SLE.

METHODSSLE-related genes were searched from the published literatures. Using the microRNA target gene prediction databases, we predicted the putative microRNA targets in these SLE-related genes. For some of the corresponding microRNAs (hsa-miR-146a), quantitative real-time polymerase chain reaction was performed to determine the expression levels of these microRNAs in PBMCs of SLE patients (SLE group) and healthy controls (control group).

RESULTThe discrepancy of cycle threshold of hsa-miR-146a in PBMCs was significantly higher in SLE group (4.52±1.18) than in control group (2.76±1.38) (P=0.02), and the expression level of hsa-miR-146a was significantly lower in SLE group.

CONCLUSIONThe expression of hsa-miR-146a decreases in SLE patients, indicating that hsa-miR-146a may play a role in the pathogenesis of SLE.

Adolescent ; Adult ; Female ; Humans ; Leukocytes, Mononuclear ; metabolism ; Lupus Erythematosus, Systemic ; genetics ; metabolism ; MicroRNAs ; genetics ; metabolism ; Young Adult

OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-systemic disease with the unknown pathogenic mechanism. DNA demethylation is involved in SLE pathogenesis. Growth arrest and DNA damage inducible 45 alpha (Gadd45a) takes part in the process of DNA demethylation. Gadd45a is a DNA repair-related protein. This study aims to investigate the expressions of some proteins [including activation-induced cytidine deaminase (AID), thymine DNA glycosylase (TDG), and methyl-CpG-binding domain protein 4 (MBD4)] involving in base excision repair (BER) process in CD4⁺ T cells in patients with SLE, and to analyze the correlations between the above BER proteins and lupus disease. METHODS: From January 2019 to September 2020, 12 SLE patients and 12 healthy controls were recruited from Second Xiangya Hospital of Central South University. Peripheral blood mononuclear cells (PBMCs) were separated by Ficoll-Hypaque density gradient centrifugation and then CD4+ T cells were isolated via positive selection using Miltenyi beads. We measured the messenger RNA (mRNA) and protein expressions of AID, TDG, and MBD4 by real-time reverse transcription polymerase chain reaction (RT-PCR) and Western blotting, respectively. RESULTS: In contrast to controls, in SLE CD4+ T cells, the mRNA and protein expressions of AID were elevated (P=0.003, P=0.022, respectively); TDG protein expression was increased (P=0.017); and MBD4 protein level was reduced (P<0.001). No visible distinctions was found in the mRNA expressions of either TDG or MBD4 between the 2 groups (both P>0.05). The mRNA and protein expressions of AID and the protein levels of TDG were positively correlated with SLE disease activity index (SLEDAI). And the mRNA and protein expressions of MBD4 were negatively correlated with SLEDAI. CONCLUSIONS In SLE CD4+ T cells, the increased expressions of AID and TDG and the decreased MBD4 expression may participate in SLE pathogenic mechanism.
Humans ; Leukocytes, Mononuclear ; Lupus Erythematosus, Systemic/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; DNA Repair ; RNA, Messenger/metabolism*

Objective To explore the role of autophagy, apoptosis of neutrophils and neutrophils extracellular traps (NET) formation in systemic lupus erythematosus (SLE). Methods Thirty-six patients with SLE were recruited as research subjects, and 32 healthy controls matched accordingly were enrolled as control subjects. The expression levels of microtubule associated protein 1 light chain 3B (LC3B), autophagy-related gene5(ATG5), P62, B-cell lymphoma 2(Bcl2), Bcl2-related X protein (BAX) in neutrophils were detected by Western blot analysis. Flow cytometry was employed to analyze the expression of LC3B on neutrophils. The expression level of myeloperoxidase(MPO) in plasma was estimated by ELISA. Furthermore, neutrophils were cultured in vitro and stimulated by 100 nmol/L rapamycin and 10 μg/mL lipopolysaccharide (LPS) for 6 hours, respectively. And then, the expression levels of LC3B, ATG5, P62, Bcl2 and BAX in neutrophils were detected by Western blot analysis. The level of MPO in culture supernatant was detected by ELISA. The change of fluorescence intensity of NET in culture supernatant was assayed by Sytox^TM Green staining combined with fluorescence spectrophotometry. Results Compared with healthy controls, the levels of autophagy and apoptosis of neutrophils and NET formation in SLE patients were increased. The level of apoptosis and NET formation was positively associated with neutrophil autophagy. The level of autophagy showed an increase but had no effect on apoptosis and NET formation for neutrophil stimulated by rapamycin. The levels of autophagy and NET formation also increased with no significant effect on apoptosis for neutrophil induced by LPS. Conclusion The autophagy, apoptosis and NET formation of neutrophils increase in SLE patients. The activation of autophagy and NET in neutrophils possibly result from the inflammatory internal environment in SLE patients.
Humans ; Neutrophils ; Extracellular Traps/metabolism* ; Lipopolysaccharides/pharmacology* ; bcl-2-Associated X Protein/metabolism* ; Sirolimus/pharmacology* ; Lupus Erythematosus, Systemic ; Autophagy

OBJECTIVETo explore the role of monocyte chemoattractant protein-1 (MCP-1) in lupus nephritis (LN).

METHODSSera MCP-1 levels were measured by enzyme linked immunosorbent assay in 112 patients with systemic lupus erythematosus (SLE), 30 patients with rheumatoid arthritis, 11 non-SLE patients with renal impairment, and 40 healthy volunteers. MCP-1 mRNA expression in peripheral blood mononuclear cells (PBMCs) was also investigated with reverse trancription-polymerase chain reaction semi-quantitative method.

RESULTSThe expression of MCP-1 was significantly higher in active LN groups than in all other groups (P < 0.001), and there was a close correlation between MCP-1 expression and the overall SLE disease activity index score (r=0.6245, P < 0.001) and the SLE disease activity index renal score (r=0.6808, P < 0.001). Low expression of MCP-1 was observed in diseased controls and healthy controls. The sera levels of MCP-1 were significantly higher in patients with active diseases than in patients with inactive SLE and controls, but no significant difference were found between the active LN groups and non-renal involvement group (P >0.05).

CONCLUSIONThe expression of PBMCs MCP-1 mRNA is upregulated in active SLE. Meanwhile, its expression levels are correlated with the activity of LN.

Adolescent ; Adult ; Aged ; Arthritis, Rheumatoid ; metabolism ; Chemokine CCL2 ; biosynthesis ; genetics ; Female ; Humans ; Lupus Erythematosus, Systemic ; metabolism ; Lupus Nephritis ; metabolism ; Male ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics

Chorea is an uncommon clinical manifestation of Sytemic lupus erythematosus (SLE). Its pathogenic mechanism has not been clearly clarified. We report a 54-year-old woman with SLE who presented with generalized chorea as an initial manifestation. Fluorine-18-fluorodeoxyglucose (FDG) PET revealed increased metabolism in the bilateral putamen. Intravenous and oral administration of steroid markedly improved chorea. Hypermetabolism of the bilateral putamen diminished on follow-up FDG-PET after the disappearance of chorea. This study suggests that chorea in SLE is associated with striatal hypermetabolism.
Administration, Oral ; Chorea* ; Female ; Fluorodeoxyglucose F18 ; Follow-Up Studies ; Humans ; Lupus Erythematosus, Systemic* ; Metabolism ; Middle Aged ; Putamen

We report a patient with systemic lupus erythematosus (SLE), who had developed metabolic alkalosis during plasmapheresis. The metabolic alkalosis could be promptly corrected by reducing the amount of citrate load. The development of metabolic alkalosis can be explained by the citrate load during plasmapheresis. Careful monitoring of acid base status is mandatory in patients with limited renal function and the reduction of citrate load may be advisable in plasmapheresis.
Adolescent ; Alkalosis/*etiology ; Citrates ; Citric Acid ; Female ; Humans ; Lupus Erythematosus, Systemic/*metabolism/therapy ; Plasmapheresis/*adverse effects/methods