Association of disease activity with depression and anxiety in systemic lupus erythematosus: A comparison of SLEDAI-2K and SLE-DAS.

OBJECTIVE: To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), with depression and anxiety in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. RESULTS: There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patients (Spearman's r = 0.764, 95% confidence interval (CI) 0.655-0.842; p< 0.001) and those with moderate-to-high disease activity (Spearman's r = 0.792, 95%CI 0.616-0.892; p< 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; p= 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (OR = 4.472, 95%CI 1.035-19.328, p= 0.045) and anxiety (OR = 3.978, 95%CI 1.051-15.049, p= 0.042). CONCLUSION: The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

OBJECTIVES: To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). METHODS: Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. RESULTS: The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. CONCLUSIONS: Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Increased interleukin-11 associated with disease activity and development of interstitial lung disease in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the association of serum interleukin-11 (IL-11) with disease activity and occurrence of interstitial lung disease (ILD) in patients with rheumatoid arthritis (RA). METHODS: One hundred and six RA patients were included, including 31 with ILD. All patients were divided into two groups according to the 28-joint Disease Activity Score (DAS28), active-disease group (DAS28>3.2) and target-achieved group (DAS28≤3.2). Serum IL-11 was detected by ELISA. Serum autoantibodies [anticitrullinated protein antibody (ACPA) and rheumatoid factor (RF)], inflammatory markers [C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)], and complete blood count were measured with routine methods. RESULTS: Serum IL-11 was upregulated in RA patients compared with healthy controls (HC), and increased more significantly in patients with ILD (RA-ILD) than patients without ILD (RA-nonILD). In both RA-ILD and RA-nonILD patients, serum level of IL-11 was higher in the active-disease group than that in the target-achieved group. Pearson correlation analysis confirmed that IL-11 was positively correlated with DAS28. No significant correlation was found between serum level of IL-11 and ACPA or RF. IL-11 was positively correlated with ESR and CRP levels and PLT count in RA patients. CONCLUSIONS: IL-11 was found to be involved in the development of arthritis and ILD in RA patients, and might constitute a potential target for the treatment of RA-ILD.

Clinical features and expression of type I interferon-inducible genes in systemic lupus erythematosus patients harboring rs1143679 polymorphism in China: a single-center, retrospective study.

OBJECTIVE: This case-control study aimed to analyze the clinical features and determine the expression of type I interferon-induced genes in systemic lupus erythematosus (SLE) patients harboring the CD11b rs1143679 single-nucleotide polymorphism (SNP) and elucidate whether it is involved in the relapses of SLE. METHODS: One hundred twenty-five relatively inactive SLE patients with SLEDAI scores < 6, including 102 CD11b rs1143679 G allele patients as controls and 23 rs1143679 A allele carriers as cases, were enrolled from the SLE patient specimen bank in the Department of Rheumatology and Immunology. The sample set was retrospectively analyzed for differences in clinical features, and quantitative PCR and Western blot analyses were performed to evaluate the relative expression of type I interferon (IFN)-inducible genes. RESULTS: The 24-h urinary protein levels in the case group were significantly elevated, and serum C3 levels were significantly reduced compared with those in the control group (P = 0.019 and P = 0.021, respectively). The relative mRNA levels of IFN-inducible genes IFIT1, IFIT4, and ISG15 in the case group were higher than that in the control group (P = 0.0257, 0.0344, and 0.0311, respectively) and matched with the Western blot results. CONCLUSIONS: The relative expression of type I IFN-inducible genes in inactive SLE patients harboring the CD11b rs1143679 polymorphism was higher than that in other lupus patients. These findings suggest that the rs1143679 SNP can precipitate relapses in inactive SLE patients. KEY POINTS: • The rs1143679 GA genotype was associated with SLE clinical features. • The rs1143679 GA genotype showed higher interferon-inducible gene expression relative to the GG genotype.

Febuxostat in the treatment of gout patients with low serum uric acid level: 1-year finding of efficacy and safety study.

To retrospectively analyze the efficacy and safety of febuxostat on gout patients with low serum uric acid level. A study was conducted in Nanjing First Hospital from October 2015 to September 2016. Thirty nine acute gouty arthritis patients from the emergency and outpatient department were included. Patients met the 2015 Gout Classification Criteria revised by American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) and had urate deposition around the joints detected by dual-energy computerized tomography (DECT). Patients whose serum uric acid (SUA) were between 5.0 and 7.0 mg/dl (300-420 µmol/l) received febuxostat treatment to maintain the SUA level between 3.0 and 5.0 mg/dl for 1 year. Efficacy and safety of febuxostat were observed during the process. Three of 39 subjects were excluded because of adverse events (AEs) after receiving an initial febuxostat treatment for 2 months. Thirty six subjects were enrolled. The mean SUA level was reduced significantly from 6.51 ± 0.28 mg/dl at baseline to 4.24 ± 0.38 mg/dl and SUA of all subjects decreased by 34.8% compared with baseline. After 1-year treatment, the volume of tophus was reduced approximately 62.8%. Serum creatinine decreased stepwise in 8 gout patients with chronic kidney diseases from 162.5 ± 9.2 µmol/l to 131.4 ± 11.0 µmol/l. Two months after initiation of treatment, the number of gout flares began to markedly decrease and almost did not occur after 1 year. After the 1-year treatment of febuxostat, the average SUA level declined significantly, and the renal function improved gradually. There was nearly complete abolition of gout flares by the end of the study. Tophi resolved markedly compared with baseline as assessed by DECT. Furthermore, only a few people experienced adverse events. Febuxostat has a notable effect for gout patients in the lower SUA level range.

(99) Tc-methylene diphosphonate improves rheumatoid arthritis disease activity by increasing the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs.

AIM: γδ T cells exhibit important functions in the pathogenesis of rheumatoid arthritis (RA). In recent years, numerous studies harnessed the γδ T cell-activating capacity of aminobiphosphonates for the treatment of malignant tumors. As (99) Tc-methylene diphosphonate ((99) Tc-MDP) has long been widely used for the treatment of RA in China with good efficacy, we are interested in whether this drug exerts its therapeutic effect on RA by modulating peripheral γδ T cells of RA patients. OBJECTIVES: To investigate the effect of (99) Tc-MDP on the frequency of γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs in the peripheral blood of patients with active RA. METHODS: Nineteen patients with active RA were treated with (99) Tc-MDP intravenously at a dose of 20 µg/day consecutively for 10-14 days. Before and after treatment, the main clinical and laboratory parameters for each patient were evaluated. The frequency of CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs was detected by flow cytometry. Serum levels of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10 and transforming growth factor (TGF)-ß were measured with enzyme-linked immunosorbent assay. RESULTS: After intravenous (99) Tc-MDP therapy, the frequency of peripheral CD3(+) γδ(+) T cells and CD4(+) CD25(+) Foxp3(+) Tregs were significantly elevated, paralleled with decreased serum levels of TNF-α and IL-6 and increased level of serum TGF-ß. The elevation of peripheral CD3(+) γδ(+) T cells was positively correlated with increased serum TGF-ß and decreased disease activity. CONCLUSION: (99) Tc-MDP may improve the activity of RA through upregulating the frequency of peripheral γδ T cells and CD4(+) CD25(+) Foxp3(+) Tregs as well as affecting the serum cytokine environment by increasing TGF-ß and decreasing TNF-α and IL-6.

Roles of γδ T cells in the pathogenesis of autoimmune diseases.

γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy.

Roles of pro- and anti-inflammatory cytokines in the pathogenesis of SLE.

SLE is an autoimmune inflammatory disease in which various pro- and anti-inflammatory cytokines, including TGF-ß, IL-10, BAFF, IL-6, IFN-α, IFN-γ, IL-17, and IL-23, play crucial pathogenic roles. Virtually, all these cytokines can be generated by both innate and adaptive immune cells and exert different effects depending on specific local microenvironment. They can also interact with each other, forming a complex network to maintain delicate immune homeostasis. In this paper, we elaborate on the abnormal secretion and functions of these cytokines in SLE, analyze their potential pathogenic roles, and probe into the possibility of them being utilized as targets for therapy.