2023 International Consensus Guidance for the use of Tripterygium Wilfordii Hook F in the treatment of active rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disorder that affects the joints and produces pain, swelling, and stiffness. It has a lifetime prevalence of up to 1% worldwide. An extract of Tripterygium wilfordii Hook F (TwHF), a member of the Celastraceae herbal family widely available in south China, has been used for treatment of RA since 1960s. METHODS: The current consensus practice guidance (CPG) aims to offer guidance on the application of TwHF in the clinical management of active RA. The CPG followed World Health Organisation (WHO)'s recommended process, carried out three systematic reviews to synthesize data from 19 randomised controlled trials (RCT) involving 1795 participants. We utilized Grading of Recommendations, Assessment, Development and Evaluation (GRADE) to evaluate certainty of evidence and derive recommendations. We rigorously followed The Appraisal of Guidelines for Research and Evaluation II (AGREE II) as conduct guides to minimise bias and promote transparency. RESULTS: There was no obvious difference between TwHF monotherapy and methotrexate (MTX) monotherapy on ACR20 (RCT = 2, N = 390, RR = 1.06, 95%CI 0.90-1.26, moderate certainty), ACR50 (RCT = 3, N = 419, RR = 1.03, 95%CI 0.80-1.34, moderate certainty), ACR70 (RCT = 2, N = 390, RR = 1.12, 95%CI 0.69-1.79, low certainty). TwHF monotherapy may be better than salicylazosulfapyridine monotherapy on ACR20 and the effect may be similar on ACR50 and ACR70. Seven RCTs compared MTX combined with TwHF versus MTX monotherapy, and the meta-analysis results favoured combination therapy group on ACR20 (RCT = 3, N = 470, RR = 1.44, 95%CI 1.28-1.62, moderate certainty), ACR50 (RCT = 4, N = 500, RR = 1.88, 95%CI 1.56-2.28, moderate certainty) and ACR70 (RCT = 2, N = 390, RR = 2.12, 95%CI 1.40-3.19, low certainty). We found no obvious difference between groups on critical safety outcomes, including infection (RCT = 3, N = 493, RR = 1.37, 95%CI 0.84-2.23), liver dysfunction (RCT = 5, N = 643, RR = 1.14, 95%CI 0.71-1.85), renal damage (RCT = 3, N = 450, RR = 2.20, 95%CI 0.50-9.72). CONCLUSION: Upon full review of the evidence, the guidance panel reached consensus on recommendations for the use of TwHF in people with active RA, either as monotherapy or as combination therapy with MTX.

The impact of diet, exercise, and sleep on Helicobacter pylori infection with different occupations: a cross-sectional study.

BACKGROUND: Associations between Helicobacter pylori infection and lifestyle factors vary greatly by geographic location. This study aims to evaluate the prevalence of Helicobacter pylori infection in the Hunan cohort of central China and analyze the associations between Helicobacter pylori infection and lifestyle factors in different occupations. METHODS: This was a cross-sectional study. Participants who received an annual physical examination were invited. Helicobacter pylori infection was detected by the 13 C-urea breath test. Self-reported physical examination questionnaires were used to analyze participants' demographic information, diet, exercise status, and sleep situations. RESULTS: 23254 participants finished this study. The Helicobacter pylori infection rate in the Hunan area was 25.8%, with the lowest prevalence in students (8.5%) and the highest prevalence in business managers (29.9%). The risk factors for Helicobacter pylori infection were marital status (divorced or married) (OR:1.16, 95%CI:1.090-1.234), overeating (OR:1.105, 95%CI: 1.001-1.220), and consumption of eggs (OR:1.047, 95%CI:1.004-1.092), animal viscera (OR: 1.077, 95%CI:1.014-1.144) and coffee (OR:1.074, 95%CI:1.019-1.132). Participants' education level (OR:0.911, 95%CI:0.881-0942), consumption of midnight snack (OR:0.926, 95%CI:0.877-0.977), and vegetable (OR:0.927, 95%CI: 0.884-0.972) were protective factors against Helicobacter pylori infection. Whether participants exercised regularly or had sleep problems had no significant effect on Helicobacter pylori infection. Different professionals showed significant differences in the rates of overeating, eating three meals on time, midnight snack, and consuming coffee, eggs, animal viscera, and vegetables > 3 times/week (P values < 0.05). CONCLUSIONS: Helicobacter pylori infection showed a significant relationship with dietary factors, but not significantly with sleep and exercise factors. Different occupations showed different dietary tendencies related to Helicobacter pylori infection. The design of an occupation-based Helicobacter pylori screening and prevention program is supported.

Association between dietary diversity, sedentary time outside of work and depressive symptoms among knowledge workers: a multi-center cross-sectional study.

BACKGROUND: Low-diversity diets and sedentary status are risk factors for depressive symptoms, while knowledge workers were ignored before. The purpose of this current study was to examine the relationship between dietary diversity, sedentary time spent outside of work, and depressive symptoms among knowledge workers. STUDY DESIGN AND METHODS: This was a multicenter and cross-sectional design that included 118,723 knowledge workers. Participants self-reported online between January 2018 and December 2020. Demographic information, the Dietary Diversity Scale, the Patient Health Questionnaire-9, dietary habits (which included eating three meals on time, midnight snacking, overeating, social engagement, coffee consumption, sugary drink consumption, smoking and alcohol use), sedentary time spent outside of work and physical activity were investigated. RESULTS: The relationships between demographic information, dietary habits and dietary diversity, and depressive symptoms were estimated. Compared with the first and second levels of dietary diversity, the third level of dietary diversity (OR: 0.91; 95% CI: 0.84-0.98) reduced the risk of depressive symptoms. Knowledge workers with different degrees of sedentary status (2-4 h (OR: 1.11; 95% CI: 1.07-1.14), 4-6 h (OR: 1.21; 95% CI: 1.17-1.26), and > 6 h (OR: 1.49; 95% CI: 1.43-1.56), presented a progressively higher risk of depressive symptoms. CONCLUSION: High amounts of sedentary time spent after work and low levels of dietary diversity are risk factors for depressive symptoms. In addition, an irregular diet and overeating are also major risk factors for knowledge workers.

Disturbance of neuron-microglia crosstalk mediated by GRP78 in Neuropsychiatric systemic lupus erythematosus mice.

OBJECTIVES: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious phenotype of systemic lupus erythematosus (SLE). The disturbance of neuron-microglia crosstalk is recently revealed in many neuropsychiatric diseases but was not well studied in NPSLE. We found glucose regulatory protein 78 (GRP78), a marker of endoplasmic reticulum stress, was significantly increased in the cerebrospinal fluid (CSF) of our NPSLE cohort. We, therefore, investigated whether GRP78 can act as a mediator between the neuron-microglia crosstalk and is involved in the pathogenic process of NPSLE. METHODS: Serum and CSF parameters were analyzed in 22 NPSLE patients and controls. Anti-DWEYS IgG was injected intravenously into mice to establish a model of NPSLE. Behavioral assessment, histopathological staining, RNA-seq analyses, and biochemical assays were performed to examine the neuro-immunological alterations in the mice. Rapamycin was intraperitoneally administered to define the therapeutic effect. RESULTS: The level of GRP78 was elevated significantly in the CSF of the patients with NPSLE. An increase in GRP78 expression, accompanied by neuroinflammation and cognitive impairment, was also found in the brain tissues of the NPSLE model mice induced by anti-DWEYS IgG deposition on hippocampal neurons. In vitro experiments demonstrated that anti-DWEYS IgG could stimulate neurons to release GRP78, which activated microglia via TLR4/MyD88/NFκB pathway to produce more pro-inflammatory cytokines and promote migration and phagocytosis. Rapamycin ameliorated GRP78-inducing neuroinflammation and cognitive impairment in anti-DWEYS IgG-transferred mice. CONCLUSION: GRP78 acts as a pathogenic factor in neuropsychiatric disorders via interfering neuron-microglia crosstalk. Rapamycin may be a promising therapeutic candidate for NPSLE.

Optogenetic stimulation of basal forebrain cholinergic neurons prevents neuroinflammation and neuropsychiatric manifestations in pristane induced lupus mice.

BACKGROUND: Neuroinflammation has been identified as one of the primary pathogenic factors of neuropsychiatric systemic lupus erythematosus (NPSLE). However, there are no dedicated treatments available in clinics to alleviate neuroinflammation in NPSLE. It has been proposed that stimulating basal forebrain (BF) cholinergic neurons may provide potent anti-inflammatory effects in several inflammatory diseases, but its potential role in NPSLE remains unexplored. This study aims to investigate whether and how stimulating BF cholinergic neurons has a protective effect on NPSLE. RESULTS: Optogenetic stimulation of BF cholinergic neurons significantly ameliorated olfactory dysfunction and anxiety- and depression-like phenotype in pristane induced lupus (PIL) mice. The increased expression of adhesion molecules (P-selectin and vascular cell adhesion molecule-1 (VCAM-1)), leukocyte recruitment, blood-brain barrier (BBB) leakage were significantly decreased. Notably, the brain histopathological changes, including the elevated levels of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1ß), IgG deposition in the choroid plexus and lateral ventricle wall and lipofuscin accumulation in the cortical and hippocampal neurons, were also significantly attenuated. Furthermore, we confirmed the colocalization between the BF cholinergic projections and the cerebral vessels, and the expression of α7-nicotinic acetylcholine receptor (α7nAChR) on the cerebral vessels. CONCLUSION: Our data indicate that stimulation of BF cholinergic neurons could play a neuroprotective role in the brain through its cholinergic anti-inflammatory effects on cerebral vessels. Therefore, this may be a promising preventive target for NPSLE.

Pristane induced lupus mice as a model for neuropsychiatric lupus (NPSLE).

BACKGROUND: The pristane-induced lupus (PIL) model is a useful tool for studying environmental-related systemic lupus erythematosus (SLE). However, neuropsychiatric manifestations in this model have not been investigated in detail. Because neuropsychiatric lupus (NPSLE) is an important complication of SLE, we investigated the neuropsychiatric symptoms in the PIL mouse model to evaluate its suitability for NPSLE studies. RESULTS: PIL mice showed olfactory dysfunction accompanied by an anxiety- and depression-like phenotype at month 2 or 4 after pristane injection. The levels of cytokines (IL-1ß, IFN-α, IFN-ß, IL-10, IFN-γ, IL-6, TNF-α and IL-17A) and chemokines (CCL2 and CXCL10) in the brain and blood-brain barrier (BBB) permeability increased significantly from week 2 or month 1, and persisted throughout the observed course of the disease. Notably, IgG deposition in the choroid plexus and lateral ventricle wall were observed at month 1 and both astrocytes and microglia were activated. Persistent activation of astrocytes was detected throughout the observed course of the disease, while microglial activation diminished dramatically at month 4. Lipofuscin deposition, a sign of neuronal damage, was detected in cortical and hippocampal neurons from month 4 to 8. CONCLUSION: PIL mice exhibit a series of characteristic behavioral deficits and pathological changes in the brain, and therefore might be suitable for investigating disease pathogenesis and for evaluating potential therapeutic targets for environmental-related NPSLE.

Hyperglobulinemia predicts increased risk of mortality in primary Sjögren's syndrome: Based on a Chinese multicentre registry.

OBJECTIVE: To investigate whether primary Sjögren's syndrome (pSS) patients with hyperglobulinemia have an increased risk of all-cause mortality. METHODS: Patients who registered in the Chinese Rheumatism Data Centre from May 2016 to July 2021 and met the 2002 American European Consensus Group criteria or 2016 American College of Rheumatology /European League Against Rheumatism classification criteria for Sjögren's syndrome were included. Hyperglobulinemia was defined as any elevated serum levels of immunoglobulin G (IgG), immunoglobulin A (IgA), or immunoglobulin M (IgM). The primary outcome was all-cause death. Data for demographic and clinical characteristics, laboratory results, disease activity, damage scores, and treatments were evaluated. RESULTS: A total of 9527 pSS patients were included in the analysis, of whom 4236 (44.5%) had at least one kind of elevated immunoglobulin level among IgG, IgA, and IgM. Patients with hyperglobulinemia had a significantly increased risk of death (crude hazard ratio 2.60; 95% confidence interval 1.91-3.55; adjusted hazard ratio 1.90; 95% confidence interval 1.20-3.01). The risk of death was positively correlated with IgG level (P trend <.001). The 5-, 10-, and 15-year survival rates of patients with hyperglobulinemia were 96.9%, 92.3%, and 87.9%, respectively, and significantly lower than the corresponding rates of 98.8%, 97.9%, and 96.4% in patients without hyperglobulinemia. CONCLUSIONS: Hyperglobulinemia is an independent risk factor for increased all-cause mortality in pSS patients. The risk of death is positively correlated with IgG level.

CMTM6: increased circulating level and up-regulated expression in labial salivary glands in patients with primary Sjogren's syndrome.

Chemokine-like factor (CKLF)-like MARVEL transmembrane domain containing family member 6 (CMTM6), which is a key regulator of programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) signaling in patients with primary Sjögren's syndrome (pSS). In this study, we analyzed the serum levels of CMTM6, PD-1, and PD-L1 in 50 patients with pSS, 42 patients with non-pSS (simply dry mouth and/or eyes symptoms) and 50 healthy controls (HC). The expression of CMTM6, PD-1, and PD-L1 in labial glands of the same 50 pSS patients and 42 non-pSS patients were assessed by immunohistochemistry (IHC). The clinical significance of CMTM6, PD-1, and PD-L1 were analyzed. We found that levels of CMTM6, PD-L1 as well as PD-1 in sera were all increased significantly in patients with pSS compared with non-pSS controls and HC. Serum CMTM6 level showed significantly correlation with PD-L1, PD-1, as well as clinical laboratory indicators and disease activity of pSS patients. CMTM6, PD-1, and PD-L1 expression in labial glands was also higher significantly in pSS patients than non-pSS controls. pSS patients with higher CM grade or ESSDAI score have higher CMTM6, PD-L1, and PD-1 expression in labial glands. These results suggest that CMTM6 may affect peripheral tolerance and lymphocytes activation by PD-1/PD-L1 pathway in sera and target tissue in pSS.

Neuropsychiatric lupus erythematosus: Focusing on autoantibodies.

Patients with systemic lupus erythematosus (SLE) frequently suffer from nervous system complications, termed neuropsychiatric lupus erythematosus (NPLE). NPLE accounts for the poor prognosis of SLE. Correct attribution of NP events to SLE is the primary principle in managing NPLE. The vascular injuries and neuroinflammation are the fundamental neuropathologic changes in NPLE. Specific autoantibody-mediated central nerve system (CNS) damages distinguish NPLE from other CNS disorders. Though the central antibodies in NPLE are generally thought to be raised from the periphery immune system, they may be produced in the meninges and choroid plexus. On this basis, abnormal activation of microglia and disease-associated microglia (DAM) should be the common mechanisms of NPLE and other CNS disturbances. Improved understanding of both characteristic and sharing features of NPLE might yield further options for managing this disease.

Increased Levels of VCAM-1 in Sera and VLA-4 Expression on Neutrophils in Dermatomyositis with Interstitial Lung Disease.

Vascular cell adhesion molecule-1 (VCAM-1) and its ligand very late antigen (VLA-4) play important roles in many autoimmune diseases. Our study aimed to investigate the serum level of VCAM-1 and VLA-4 expression on peripheral blood neutrophil surface in patients with dermatomyositis (DM), especially focusing on patients with interstitial lung disease (ILD). Blood specimens of 42 patients with DM and 42 healthy controls matched for age and gender were recruited. Total serum VCAM-1 level was measured using commercial enzyme-linked immunosorbent assay (ELISA) and the percentages of VLA-4 expression on neutrophils were analyzed by flow cytometry. We divided patients into subgroups according to whether they had ILD and whether they exhibited diffuse alveolar damage (DAD) via high-resolution computed tomography (HRCT). sVCAM-1 was increased in classical DM (cDM) and clinical amyopathic dermatomyositis (CADM) compared with healthy controls (both p < .01). DM-ILD had higher sVCAM-1 levels than the none-ILD group (p < .01). sVCAM-1 was also significantly increased in the DAD group compared to the none-DAD group (p < .01). The percentages of VLA-4 expression on neutrophils in cDM and CADM patients were significantly elevated than that in healthy controls (both p < .01). The percentage of VLA-4 expression on neutrophils in DM patients with ILD was higher than none-ILD group (p < .01). In the patients with ILD, DAD group had a higher percentage of VLA-4 expression on neutrophils than none-DAD group (p < .01). Our findings indicated that serum VCAM-1 levels combined with VLA-4 expression on neutrophils might be useful for detecting the severity of lung disease in patients with DM.

The association of carotid artery atherosclerosis with the estimated excretion levels of urinary sodium and potassium and their ratio in Chinese adults.

BACKGROUND: Arterial stiffness is an independent cardiovascular risk factor. However, the association between sodium/potassium intake and vascular stiffness was inconsistent. Therefore, a large community-based cross-sectional study was performed to try and achieve more definitive conclusion. METHODS: Urinary sodium, potassium, and creatinine levels were tested in spot urine samples during physical examinations of each recruited participant. The 24-h estimated urinary sodium excretion (eUNaE) and estimated urinary potassium excretion (eUKE) levels were determined using the Kawasaki formula (used as a surrogate for intake). Carotid intima-media thickness (IMT) and plaques were measured using ultrasound. RESULTS: In 13,523 subjects aged 18-80 years, the relationships between carotid plaques and IMT with eUNaE, eUKE and their ratios were analyzed. Overall, 30.2% of participants were diagnosed with carotid artery plaques. The ratio of estimated sodium vs. potassium excretion (Na/K ratio) of the individuals with carotid artery plaques was significantly higher than that of participants without plaque (2.14 ± 0.73 vs. 2.09 ± 0.61, P < 0.01). After adjusting for age, gender, and other lifestyle covariates, a significant positive relation was found between carotid plaque and Na/K ratios (OR = 1.06, P < 0.05). In participants without plaque, a similar positive association was observed between Na/K ratios and increased bifurcation carotid IMT (ß = 0.008, P < 0.01), especially in the females (Pinteraction < 0.01). CONCLUSIONS: In this study, in which sodium intake was estimated on the basis of measured urinary excretion, high estimated excretion levels of urinary sodium and/or low estimated excretion levels of urinary potassium might be associated with an increased presence of carotid atherosclerosis in Chinese individuals.

Neuroprotective effect of microglia against impairments of auditory steady-state response induced by anti-P IgG from SLE patients in naïve mice.

OBJECTIVE: Autoantibodies against ribosomal P proteins (anti-P antibodies) are strongly associated with the neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE). The present study was designed to assess whether anti-P antibodies can induce abnormal brain electrical activities in mice and investigate the potential cytopathological mechanism. METHODS: Affinity-purified human anti-ribosomal P antibodies were injected intravenously into mice after blood-brain barrier (BBB) disruption. The auditory steady-state response (ASSR) was evaluated based on electroencephalography (EEG) signals in response to 40-Hz click-train stimuli, which were recorded from electrodes implanted in the skull of mice. Immunofluorescence staining was used to examine the morphology and density of neurons and glia in the hippocampus and cortex. The presence of apoptosis in the brain tissues was studied using the TUNEL assay. A PLX3397 diet was used to selectively eliminate microglia from the brains of mice. RESULTS: Circulating anti-P antibodies caused an enhancement of the ASSR and the activation of microglia through the disrupted BBB, while no obvious neural apoptosis was observed. In contrast, when microglia were depleted, anti-P antibodies induced a serious reduction in the ASSR and neural apoptosis. CONCLUSION: Our study indicates that anti-P antibodies can directly induce the dysfunction of auditory-evoked potentials in the brain and that microglia are involved in the protection of neural activity after the invasion of anti-P antibodies, which could have important implications for NPSLE.

The association of blood pressure with estimated urinary sodium, potassium excretion and their ratio in hypertensive, normotensive, and hypotensive Chinese adults.

BACKGROUND AND OBJECTIVES: Low sodium and high potassium intake is reported to be a risk of hypertension. However, it is uncertain whether these associations can be generalized to those without hypertension. This study is to evaluate the associations of systolic and diastolic blood pressure (SBP and DBP, respectively) with estimated urinary sodium excretion (eUNaE), estimated urinary potassium excretion (eUKE) and their ratio (Na/K ratio) among hypertensive, normotensive, and hypotensive Chinese individuals. METHODS AND STUDY DESIGN: A large institution-based cross-sectional study was conducted at the Third Xiangya Hospital, Changsha between August 2017 and November 2018. Spot urine samples were collected to test urinary sodium, potassium, and creatinine excretions for each participant. The Kawasaki formula was used to estimate 24-hour urinary sodium and potassium excretions. RESULTS: A total of 26,363 eligible subjects were used to analyze the associations of blood pressure with eUNaE, eUKE, and their ratio. 27.3% (n=7,201) of participants were diagnosed with hypertension, 5.4% (n=1,427) were diagnosed with hypotension, and the remaining of 17,735 participants were normotensive. A significant increase in SBP and DBP was related to the Na/K ratio increase in hypertensive and normotensive subgroups (all ptrend<0.01), but the association was not significant for DBP among hypotensive individuals (ptrend=0.58). Stronger associations of SBP with the Na/K ratio were observed in older people (pinteraction<0.01) and females (pinteraction<0.0001), but the same trend was not observed for DBP (pinteraction=0.10 and 0.88, respectively). CONCLUSIONS: High potassium and low sodium intake were further confirmed to reduce blood pressure in hypotensive, normotensive, and hypertensive individuals.

Associations of vitamin D with novel and traditional anthropometric indices according to age and sex: a cross-sectional study in central southern China.

PURPOSE: Vitamin D insufficiency and obesity are recognized as worldwide concerns and have been linked with each other. New anthropometric indices reflect visceral obesity better than traditional anthropometric indices. Our aim was to identify the specific correlations of novel and traditional anthropometric indices with 25-hydroxyvitamin D (25(OH)D) concentrations by sex and age. METHODS: Cross-sectional data on sociodemographic characteristics, lifestyle factors, clinical characteristics and biochemical measurements were collected for 12,617 Chinese adults. Four traditional anthropometric indices, body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR), and two novel anthropometric indices, body roundness index (BRI) and body shape index (ABSI), were calculated. RESULTS: In both sexes, the mean values of BMI, WC, WHtR and BRI tended to increase with 25(OH)D insufficiency, regardless of adjustment (all P < 0.05). Males with insufficient 25(OH)D had increased odds of obesity (assessed by BMI, WC, WHtR, BRI and ABSI) compared to the odds of males with sufficient 25(OH)D. Females with insufficient 25(OH)D had a higher chance of general obesity (assessed by BMI). Low 25(OH)D status was associated with indicators of obesity only in participants aged 45-64 years in both sexes. CONCLUSION: A inverse association between obesity and lower vitamin D levels was found. Moreover, in addition to BMI, novel indicators of visceral adiposity, such as BRI and ABSI, were associated with lower 25(OH)D serum concentrations in males. The effects of optimizing vitamin D levels in obese Chinese adults need further examination, particularly in middle-aged males. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Lupus serum IgG induces microglia activation through Fc fragment dependent way and modulated by B-cell activating factor.

BACKGROUND: Neuropsychiatric manifestations are frequent in patients with systemic lupus erythematosus (SLE), yet the etiology and pathogenesis of brain damage in SLE remains unclear. Because the production of autoantibodies, formation and deposition of immunocomplexes are major serological characteristics of SLE, the elevated level of serum immunoglobulin may contribute to brain tissue injury of SLE. To testify this, in this study, we examined whether immunoglobulin G (IgG) in the serum of SLE patients affects the cellular functions in central nervous system and the potential mechanism. METHODS: In vivo intracerebral injection of SLE-serum in mouse was used to activate microglia and the production of pro-inflammatory cytokine was assessed by ELISA. Sera was divided into IgG and IgG depleted fractions, while IgG was further divided into Fc and Fab fragments to examine which part has an effect on microglia. Flow cytometry, immunofluorescence and quantitative PCR (qPCR) were used to verify the synergistic effect of B-cell activating factor (BAFF) on IgG stimulation of microglia. RESULTS: We found that IgG in lupus sera can induce M1 activation of brain microglia following intraventricular injection into normal mice, and BAFF facilitates this process. In vitro, we identified that IgG bound to microglia through Fc rather than Fab fragments, and BAFF up-regulated the expression of Fc receptors (FcγR) on the surface of microglia, consequently, promote IgG binding to microglia. CONCLUSION: Our results suggest that lupus serum IgG causes inflammatory responses of microglia by involving the Fc signaling pathway and the activity could be up-regulated by BAFF. Accordingly, disruption of the FcγR-mediated signaling pathway and blockade of microglia activation may be a therapeutic target in patients with neuropsychiatric lupus erythematosus.

Peripheral blood brain-derived neurotrophic factor level and tyrosine kinase B expression on T lymphocytes in systemic lupus erythematosus: Implications for systemic involvement.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) has been reported to be involved in the pathogenesis of autoimmune diseases and tyrosine kinase B (TrkB) is the specific receptor for BDNF. Our aim in this study was to investigate serum BDNF level and TrkB expression on peripheral blood T cell surface in patients with systemic lupus erythematosus (SLE) and explore potential relationship between serum BDNF and SLE. METHODS: Samples from fifty SLE patients and thirty healthy controls were evaluated. Serum BDNF level was measured by enzyme-linked immunosorbent assay (ELISA) and the percentages of TrkB expression on the surface of CD3 + CD4 + and CD3 + CD8 + T lymphocytes were measured by flow cytometry. The SLE patients were divided into subgroups according to whether they exhibited brain, kidney or lung involvement, and whether the disease was active or inactive. RESULTS: Serum BDNF levels in SLE patients were decreased when compared to the controls (p < 0.001). Comparing with the SLE individuals without systemic involvement, the BDNF levels were decreased in SLE patients with lupus nephritis (p = 0.042) and in SLE patients with neuropsychiatric manifestations (p = 0.04). On the other hand, the BDNF level was significantly increased in the inactive SLE group (p < 0.001) compared to the active SLE group. In addition, the percentages of TrkB expression on CD3 + CD4 + and CD3 + CD8 + T cell surface in SLE were significantly higher (p < 0.001; p < 0.001, respectively) than that in the controls. CONCLUSIONS: Serum BDNF level combined with TrkB expression on T cell surface can reflect SLE activity. It is possible that BDNF may be used as a potential serological biomarker for disease activity of SLE. In addition, the significant decrease in serum BDNF level may imply systemic involvement of SLE, as well as, possibly, differentiate neuropsychiatric SLE from hormone-induced mental disorders.

Salt intake assessed by spot urine on physical examination in Hunan, China.

BACKGROUND AND OBJECTIVES: Excessive salt intake is a major public health problem in several countries, especially in China. However, few people are aware of their salt intake. The purpose of this study is to carry out salt intake test in routine physical examination, and to explore the salt intake of different populations and their correlation with diet. METHODS AND STUDY DESIGN: Spot urine sample was collected to test urinary sodium and creatinine excretions for each participant recruited from physical examinations at the Third Xiangya Hospital. The Tanaka formula was used to estimate 24-h urinary sodium excretion, which reflects salt intake. In addition to physical and laboratory examination, information including personal details, health-related habits, and selfreported disease histories was obtained from the National Physical Examination Questionnaire. RESULTS: In total, 26,406 people completed the salt intake evaluation. After data cleansing, the average salt intake was 8.39±1.80 g/d. Male, middle-aged, overweight and obese, hypertensive, and dyslipidaemic populations, as well as those with non-cardiovascular diseases were more likely to have excessive salt intake. Dietary sources had an effect on salt intake. Salt intake was lower in those who consumed more milk and fruit (both p and p trend<0.01) but was higher in those who consumed more lean meat (both p and p trend<0.05), fatty meat (both p and p trend<0.01) and animal organs (both p and p trend<0.01). CONCLUSIONS: The salt intake in this population far surpasses the recommended amount. We strongly recommend salt intake assessment as routine test into physical examination center.

Increased frequency of CCR7+CD4+ T cells from patients with primary Sjögren's syndrome: An indicator of disease activity rather than of damage severity.

Expression of CCR7 on T cells has been reported to be associated with the lymphocytic migration and infiltration, which is recognized as a vital part of the pathogenesis of Primary Sjögren's syndrome (pSS). Here, we compared the expression of CCR7 on CD4+T cells between pSS patients and control groups, including healthy donors (HD) and patients with systemic lupus erythematosus (SLE) and examined correlations with disease activity and damage severity, which were evaluated by EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) and Sjogren's Syndrome Disease Damage Index (SSDDI), respectively. Peripheral blood mononuclear Cells (PBMC) were obtained from patients and controls and expressions of CCR7 were evaluated by flow cytometry. CCR7 was selectively and frequently expressed on CD4+T cells, but less on CD8+ T cells of patients with pSS. In contrast, this phenomenon was neither seen in normal subjects nor in patients with SLE. The expression level of CCR7 in the peripheral blood CD4+ T cells is closely correlated with ESSDAI, but not SSDDI. Correspondently, the chemotactic index (CI) of CD4+T cells was higher than CD8+T cells in patients with pSS. Furthermore, the CI of CD4+T cells is also higher than that of other controls, which is correlated with ESSDAI. All the findings suggested that CCR7 might play an important role in the development of pSS by mediating the migration of CD4+cells. Thus, the expression of CCR7 in CD4+ T cells is probably a useful biomarker to evaluate and monitor disease activity. CCR7 can also potentially be a novel target for the therapy of pSS.

Altered chemokine receptor expression in the peripheral blood lymphocytes in polymyositis and dermatomyositis.

OBJECTIVE: To examine the expression of chemokine receptors in different peripheral blood T-cell subsets in patients with polymyositis (PM) and dermatomyositis (DM). METHODS: We used flow cytometry to measure the frequencies of chemokinereceptors CXCR3 and CCR4 expression in the CD4+ or CD8+ lymphocytes. Enzyme linked immunosorbent assays were also used to measure the concentrations of C-X-C motif chemokine 10 (CXCL10), thymus and activation regulated chemokine (TARC) and macrophage derived chemokine (MDC). RESULTS: Comparing to 20 healthy controls, %CD4+CXCR3+ and %CD8+CXCR3+ T cells significantly decreased in 33DM patients, and %CD8+CXCR3+ cells decreased in 24PM patients, but %CD4+CCR4+ and %CD8+CCR4+ cells did not significantly change in both the PM and DM patients. Accordingly, the Th1/Th2 polarization, analyzed as the balance obtained after dividing %CD4+CXCR3+ cells by %CD4+CCR4+ cells, showed a significant reduction in DM. The serum concentration of CXCR3+ ligand, CXCL10, significantly increased and negatively correlated with circulating %CD4+CXCR3+ cells in DM patients. There was no significant change of TARC and MDC in PM and DM patients. Furthermore, %CD4+CXCR3+ cells decreased more severely in the patients with interstitial lung disease. CONCLUSIONS: The present results indicate that the distributions of circulating CXCR3+ T-cells differ among the PM and DM cases. Our findings suggest a pathogenic difference between PM and DM.