Although CD3-CD56+NKp44+ natural killer (NKp44+NK) cells have been linked to autoimmune diseases including inflammatory bowel disease, ankylosing spondylitis, and primary Sjogren syndrome, the expansion and role of those cells in patients with rheumatoid arthritis (RA) remain less defined. Here, we investigate the proportion and pathogenesis of NKp44+NK cells in patients with RA. The results show NKp44+NK cells significantly expanded in RA peripheral blood and synovial fluid, which were correlated positively with RA disease activity. They also highly expressed in RA synovial tissues and secreted a high concentration of interleukin-22 (IL-22) in vitro. Further, NKp44+NK cells culture supernatant promoted the proliferation of fibroblast-like synoviocytes (FLS) which was blocked by IL-22 antagonist and AG490. Treated with recombination human IL-22, the proliferation and phosphorylation-STAT3 on RA-FLS increased in a dose-dependent manner and time-dependent manner; the progress of which could be blocked by AG490. The present study clarifies the expansion of NKp44+NK cells in the peripheral blood and synovial fluid of patients with RA, especially in the synovial tissues of RA for the first time. STAT3 is an essential pathway in mediating the effects of IL-22 secreted by NKp44+NK cells on the proliferation of FLS in patients with RA.
The aim of this study was to discuss the diagnostic value of dual-energy computed tomography (DECT) in patients with gout during different disease phases. Two hundred twenty-one patients (136 with gout and 85 with other arthritic diseases) were recruited to the study. Arthrosis pain was evaluated in all patients by DECT scans. We calculated the sensitivity and specificity of DECT for the diagnosis of gout, including the first onset period, less than 24 months period, and more than 24 months period. We then investigated the related risk factors of urate crystals volume in the foot. The diagnostic sensitivity of DECT in the first onset, less than 24 months, and more than 24 months groups was 35.71, 61.54, and 92.86%, respectively. The overall sensitivity and specificity values were 80.88 and 88.24%, respectively. The multilinear regression analysis showed that longer disease duration (P = 0.001) and higher serum uric acid (SUA) (P = 0.001) were the two important predictive factors of the monosodium urate (MSU) crystal volume in the foot. DECT provides good diagnostic accuracy for detection of MSU crystal deposits in gout patients. However, DECT has limited diagnostic sensitivity for short-term gout patients, especially for the first onset patients. Longer disease duration and higher SUA were predictive factors of MSU crystal volume.
Objective To investigate cardiac manifestations and the risk factors in Han Chinese patients with systemic lupus erythematosus (SLE). Methods Seven hundred fifty SLE patients who were hospitalized at our department were recruited in the present study. The patients were divided into two groups-those with or without cardiac manifestations. Cardiac manifestations in those SLE patients, such as pericarditis, myocarditis, heart valve disease, arrhythmia, were analyzed. The risk and protective factors of cardiac diseases in patients with SLE, as well as the predictors of mortality, were assessed, respectively. Results In all 750 SLE patients, there were 339 (45.20%) patients suffered from one or more cardiac manifestations, involving pericarditis in 9.5%, myocarditis in 5.7%, heart valve disease in 15.6%, arrhythmia in 16.67%, and cardiovascular diseases (CVD) in 14%. 15.7% of SLE patients were accompanied with pulmonary arterial hypertension (PAH), of which 13.7% were mild, 1.2% were moderate, and 0.8% were severe. No significant differences were found between the two groups in age, disease duration, gender, antibody, and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The incidence of pericarditis, heart valve disease, arrhythmia, and PAH was positively correlated with age. The incidence of arrhythmia, CVD, and PAH was correlated with SLEDAI. PAH and myocarditis were the risk factors of mortality in SLE patients with disease duration ≤ 10 years (P = 0.034 and 0.001, respectively). Conclusion Cardiac involvement is common in Han Chinese SLE patients and associated with age and disease activity. PAH and myocarditis are the risk factors of mortality in SLE.
Anti-small ubiquitin-like modifier-1 activating enzyme (anti-SAE) antibodies have been recently discovered especially for myosin and identified as dermatomyositis (DM) marker. The frequency of anti-SAE antibodies in DM patients is extremely low. Diffuse pruritic erythema may be one kind of clinical manifestations of DM with anti-SAE antibodies. In this report, a 48year-old female patient with amyopathic dermatomyositis (ADM) carrying anti-SAE antibodies presented diffuse pruritic erythema for 5 months. Diffuse pruritic erythema improved after treatment with prednisolone, cyclosporine, and thalidomide. The clinical characteristics of 75 previously reported cases with anti-SAE antibody-positive DM were reviewed, and the manifestations of the Asian and Western cohorts were compared. It was revealed that the Asian patients were more susceptible to diffuse erythema (17/34 vs. 3/41, P = 0.000), dysphagia (16/34 vs. 10/41, P = 0.040), and interstitial lung disease (ILD) (21/34 vs. 5/41, P = 0.000) compared with the Western patients. The frequency of malignancy in the Asian cohort was significantly higher than that in the Western cohort (10/34 vs. 4/41, P = 0.030).
BackgroundPrevious studies have revealed that ankylosing spondylitis (AS), as the progenitor of axial spondyloarthritis (AxSpA), has been characterized by the insidiously progressive nature of sacroiliitis and spondylitis. Dual-energy computed tomography (DECT) has recently been used to analyse the deposition of monosodium urate (MSU) crystals with higher sensitivity and specificity. However, it remains unclear whether the existence of the MSU crystal deposition detected by DECT at the sacroiliac joint in patients with AxSpA also is associated with the existing structural damage. Here, we performed this study to show the DECT MSU crystal deposits in AxSpA patients without coexisting gout and to ascertain the relationship between the MSU crystal deposition and the structural joint damage of sacroiliac joints.MethodsOne hundred and eighty-six AxSpA patients without coexisting gout were recruited. The plain radiographs of the sacroiliac joint were obtained, along with the DECT scans at the pelvis and the clinical variables. All statistics based on the left or right sacroiliac joint damage grading (0–4) were calculated independently. Bivariate analysis and ordinal logistic regression was performed between the clinical features and radiographic grades at the sacroiliac joint.ResultsAt the pelvis, large quantities of MSU crystal deposition were found in patients with AxSpA. The average MSU crystal volume at the left sacroiliac joint, the right sacroiliac joint, and the pelvis were 0.902 ± 1.345, 1.074 ± 1.878, and 5.272 ± 9.044 cm3, values which were correlated with serum uric acid concentrations (r = 0.727, 0.740, 0.896; p < 0.001). In bivariate analysis, wide clinical variables were associated with the changes in sacroiliac joint damage. Further, the AxSpA duration, BASFI score, and the volume of MSU crystal at both sides of sacroiliac joint were associated with the progress of radiographic grade at the sacroiliac joints in the ordinal logistic models (left AOR = 1.180, 3.800, 1.920; right AOR = 1.190, 3.034, 1.418; p < 0.01).ConclusionsLarge quantities of MSU crystal deposition detected by DECT were found at the pelvis in AxSpA patients without coexisting gout. In addition to AxSpA duration and BASFI score, the MSU crystal deposition at the sacroiliac joint is associated with the progress of radiographic grade at sacroiliac joints in those patients.
Gout has become a public health problem that seriously threatens human health. Traditional Chinese medicines (TCMs) have a long history of treating gout and have some advantages compared with the conventional medicines. Compound TCM Tongfengtai granules are gradually being used for clinical treatment of gout, but its mechanism is still unclear. The purpose of this study was to explore the metabolic profiling of serum from gout patients before and after treatment with Tongfengtai granules and identify the differential metabolites and related metabolic pathways. A total of 40 gout patients hospitalized in Shenzhen Traditional Chinese Medicine Hospital from 2018 to March 2019 were recruited in the current study, and serum samples from these patients before and after treatment with Tongfengtai granules were collected. Gas chromatography-mass spectrometry (GC-MS) assay was used to identify serum metabolites. The OPLS-DA VIP method was used to screen for potential metabolic biomarkers, and MetaboAnalyst 4.0 was used to identify related metabolic pathways. The result showed that there was a significant difference in the concentrations of six metabolites in the serum after treatment: D-galactose, lactic acid, 3-hydroxybutyric acid, D-pyran (type) glucose, alanine, and L-isoleucine. Except D-pyran (type) glucose, the serum concentrations of the other five metabolites were all significantly reduced. Besides, pathway enrichment analysis found that these potential metabolic biomarkers were mainly involved in lactose degradation and the glucose-alanine cycle. Thus, the serum metabolic profiling of gout patients treated with Tongfengtai granules changed, and the differential metabolites and related metabolic pathways might provide clues for understanding the mechanism of Tongfengtai granules.
Background and ObjectiveBone erosion is common in patients with gout. The role of neutrophil-derived exosomes in gouty bone erosion remains elusive. This study aimed to investigate the functions of the neutrophil-derived exosomes in the development of bone erosion in gout.MethodsNeutrophil-derived exosomes were collected and assessed by transmission electron microscopy and nanoparticle tracking analysis. Cell counting kit-8 assay was applied to evaluate cell viability, and cell apoptosis was assessed by flow cytometry. In addition, quantitative Real-time PCR and Western blotting were used to determine the expression levels of alkaline phosphatase (ALP), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL). Neutrophil-derived exosomes were tagged with PKH67. The miRNA expression profiles of exosomes and human fetal osteoblasts (hFOB) were compared using high-throughput sequencing. Functional miRNAs transfected into hFOB after co-incubation with exosomes were selected and validated by preliminary qPCR.ResultsNeutrophil-derived exosomes were stimulated by monosodium urate (MSU). The exosomes could inhibit the viability of the hFOB, and the expression levels of ALP and OPG were down-regulated, while the expression level of RANKL was up-regulated. However, there was no significant difference in the viability of osteoclasts and the expression of nuclear factor of activated T cells 1. Exosomes were observed in the cytoplasm under a confocal microscopy, confirming that exosomes could be taken up by hFOB. In total, 2590 miRNAs were found, of which 47 miRNAs were differentially expressed. Among the delivered miRNAs, miR-1246 exhibited the highest level of differential expression. The viability of hFOB was reduced by miR-1246 mimics and increased by miR-1246 inhibitors. There was no significant difference in hFOB apoptosis rate between the miR-1246 mimic and miR-1246 inhibitor group. MiR-1246 overexpression decreased the expression levels of ALP and OPG, whereas increasing the expression level of RANKL. In contrast, miR-1246 inhibitor increased the expression levels of ALP and OPG, while decreasing the expression level of RANKL. Neutrophil-derived exosomes stimulated by MSU could increase the expression of miR-1246. ConclusionNeutrophil-derived exosomes stimulated by MSU could inhibit the viability of osteoblasts.
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