[Low disease activity and remission status of systemic lupus erythematosus in a real-world study].

OBJECTIVE: To investigate the rates of low disease activity and clinical remission in patients with systemic lupus erythematosus (SLE) in a real-world setting, and to analyze the related factors of low disease activity and clinical remission. METHODS: One thousand patients with SLE were enrolled from 11 teaching hospitals. Demographic, clinical and laboratory data, as well as treatment regimes were collec-ted by self-completed questionnaire. The rates of low disease activity and remission were calculated based on the lupus low disease activity state (LLDAS) and definitions of remission in SLE (DORIS). Charac-teristics of patients with LLDAS and DORIS were analyzed. Multivariate Logistic regression analysis was used to evaluate the related factors of LLDAS and DORIS remission. RESULTS: 20.7% of patients met the criteria of LLDAS, while 10.4% of patients achieved remission defined by DORIS. Patients who met LLDAS or DORIS remission had significantly higher proportion of patients with high income and longer disease duration, compared with non-remission group. Moreover, the rates of anemia, creatinine elevation, increased erythrocyte sedimentation rate (ESR) and hypoalbuminemia was significantly lower in the LLDAS or DORIS group than in the non-remission group. Patients who received hydroxychloroquine for more than 12 months or immunosuppressant therapy for no less than 6 months earned higher rates of LLDAS and DORIS remission. The results of Logistic regression analysis showed that increased ESR, positive anti-dsDNA antibodies, low level of complement (C3 and C4), proteinuria, low household income were negatively related with LLDAS and DORIS remission. However, hydroxychloroquine usage for longer than 12 months were positively related with LLDAS and DORIS remission. CONCLUSION: LLDAS and DORIS remission of SLE patients remain to be improved. Treatment-to-target strategy and standar-dized application of hydroxychloroquine and immunosuppressants in SLE are recommended.

Prevalence of psychological disorders, sleep disturbance and stressful life events and their relationships with disease parameters in Chinese patients with ankylosing spondylitis.

Our aim was to investigate the prevalence of psychological disorders, sleep disturbance, and stressful life events in Chinese patients with ankylosing spondylitis (AS) and healthy controls, to assess the correlation between psychological and disease-related variables, and finally to detect powerful factors in predicting anxiety and depression. AS patients diagnosed with the modified New York criteria and healthy controls were enrolled from China. Participants completed a set of questionnaires, including demographic and disease parameters, Zung self-rating anxiety scale (SAS), Zung self-rating depression scale (SDS), the Pittsburgh Sleep Quality Index questionnaire (PSQI), and the Social Readjustment Rating Scale (SRRS). The relationship between psychological and other variables was explored. Stepwise multiple regression was used to determine the contributors to each disorder. Of all the 2772 AS patients, 79.1% were male. Mean age was 28.99 ± 8.87 years. Prevalence of anxiety, depression, and sleep disturbance was 31.6% (95% CI, 29.9, to 33.4), 59.3% (95% CI, 57.5, to 61.2), and 31.0% (95% CI, 29.3, to 36.7), respectively. 35.3% had stimulus of psychological and social elements (SPSE). Compared with healthy controls, AS patients had more severe psychological disorders, sleep disturbance, and stressful life events (P < 0.01). SDS, overall pain, BASFI, and sleep disturbance were significant contributors of the SAS scores (P < 0.03). SAS, less years of education, and sleep duration were significant contributors of SDS (P < 0.01). AS patients had more anxiety, depression, stressful life events, and sleep disturbance than healthy controls. Pain, functional limitation, sleep disturbance, and education were major contributors to psychological disorders.

The relationship between disease activity measured by the BASDAI and psychological status, stressful life events, and sleep quality in ankylosing spondylitis.

Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is a standard instrument regularly used to assess disease activity of patients with ankylosing spondylitis (AS). However, the well-being of a patient is also affected by impairment of function as well as psychological status and other factors. The objective of this study was to evaluate if psychological status, stressful life events, and sleep quality contribute significantly to BASDAI. Six hundred eighty-three AS patients satisfying the Modified New York Criteria for AS were recruited from the rheumatology clinics of seven hospitals in China. Patients with other concomitant disorders were excluded. Participants were requested to complete a set of clinical examinations and the following questionnaires: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Bath Ankylosing Spondylitis Functional Index (BASFI), Zung Self-Rating Anxiety Scale (SAS), Zung Self-Rating Depression Scale (SDS), Pittsburgh Sleep Quality Index Questionnaire (PSQI), Health Assessment Questionnaire for Spondyloarthropathies (HAQ-S), and Social Readjustment Rating Scale (SRRS). Spearman correlation analysis showed that BASDAI was highly associated with degree and duration of morning stiffness, overall pain, nocturnal back pain, overall back pain, anxiety, and BASFI (all P < 0.001), but were not associated with education, HAQ-S, and sleep medication in PSQI (P > 0.05). Multiple stepwise regression analysis indicated that overall pain was the maximal statistical contribution in predicting disease activity (standardized coefficient, 0.335). In hierarchic multiple regression analysis, psychological variables added an only additional 2.7% to the overall R(2) beyond that accounted for by demographic and medical variables, resulting in a final R(2) of 53.5%. Although BASDAI is a very good measurement of pain and stiffness and to a certain extent effect of functional impairment in AS, it barely takes into account psychological status, stress life events, and sleep quality These factors should be evaluated by other modalities.

The CD226 gene in susceptibility of rheumatoid arthritis in the Chinese Han population.

Recent case-control studies have identified some loci that are associated with rheumatoid arthritis (RA). Among these, a single nucleotide polymorphism (SNP), Gly307Ser (rs763361), in the CD226 gene was first discovered to confer the risk of RA in populations with European and Colombian ancestry. Because the effect of genetic factors varies in different races, the association between RA and CD226 is yet to be evaluated in other non-European populations. Here, we report the significant association between CD226 and RA in a Chinese population of 423 randomly enrolled individuals. The statistical results show that the rs763361 SNP in the CD226 gene is significantly associated with RA in the Chinese population group (P (obs) = 0.005, odds ratio = 1.52). After adjusting for sex and age using multivariate logistics regression analysis, the association is still positive (P (adj) = 0.029, odds ratio = 1.45). Meta-analysis confirms the association between rs763361 and RA (overall P < 0.001, overall odds ratio = 1.12). The test of odds ratio heterogeneity also suggests that the rs763361 SNP confers the same risk of RA in both the Chinese and the Colombian populations, and indicates that rs763361 may play a more important role in non-European populations compared with the European population (P = 0.031). These results demonstrate a genetic association between the CD226 gene and RA in a Chinese Han population with a potentially greater genetic effect than in the European population.

A genome-wide association study in Han Chinese identifies new susceptibility loci for ankylosing spondylitis.

To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.

Relatively increased number of liver Foxp(3+) regulatory T cells against hepatic lesions in murine lupus.

Systemic lupus erythematosus (SLE) is a multiple organ autoimmune disorder, including the liver, but the possible reason in impairment in the liver is still unclear. Our present study assessed alterations of transcription factor Foxp3(+) regulatory T cells (Tregs) and several other immune molecules [programmed cell death 1 and its ligand (PD1 and PD-L1), and interleukin 10 (IL-10) and transform growth factor ß (TGF-ß)] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry, real-time quantitative reverse transcription PCR, and enzyme-linked immunosorbent assay. Results showed that both frequency and number of Foxp3(+) Tregs were dramatically reduced in the thymus, spleen and kidney of the BXSB mice (P<0.05), but those in the liver were kept in nearly normal range, when compared to negative control C57BL/6 mice. In comparison to control mice, the mRNA levels of Foxp3, PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice (P<0.05), but there was no significant difference in the livers of the BXSB mice (P>0.05). Protein levels of IL-10 and TGF-ß in serum showed no significant difference between BXSB and C57BL/6 mice, but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice (P<0.05). These results suggest that reduced Foxp3(+) Tregs are involved in the pathogenesis of SLE in BXSB mice, and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice, which may provide insights into development of new therapeutic approaches in SLE patients.

Relatively Increased Number of Liver Foxp3+ Regulatory T Cells against Hepatic Lesions in Murine Lupus / 华中科技大学学报（医学）（英德文版）

Systemic lupus erythematosus (SLE) is a multiple organ autoimmune disorder,including theliver,but the possible reason in impairment in the liver is still unclear.Our present study assessed alterations of transcription factor Foxp3+ regulatory T cells (Tregs) and several other immune molecules [programmed cell death 1 and its ligand (PD1 and PD-L1),and interleukin 10 (IL-10) and transform growth factor β (TGF-β)] in the liver and other major organs of lupus-prone BXSB mice by flow cytometry,real-time quantitative reverse trinscription PCR,and enzyme-linked immunosorbent assay.Results showed that both frequency and number of Foxp3+ Tregs were dramatically reduced in the thymus,spleen and kidney of the BXSB mice (P＜0.05),but those in the liver were kept in nearly normal range,when compared to negative control C57BL/6 mice.In comparison to control mice,the mRNA levels of Foxp3,PD1 and PD-L1 were significantly decreased in the kidneys of BXSB mice (P＜0.05),but there was no significant difference in the livers of the BXSB mice (P＞0.05).Protein levels of IL-10 and TGF-β in serum showed no significant difference between BXSB and C57BL/6 mice,but were significantly increased in the kidneys and livers of BXSB mice as compared with those in C57BL/6 mice (P＜0.05).These results suggest that reduced Foxp3+ Tregs are involved in the pathogenesis of SLE in BXSB mice,and relatively higher number of these cells in the livers than in the other target organs could constitute a protective mechanism against hepatic lesions in lupus-prone mice,which may provide insights into development of new therapeutic approaches in SLE patients.

Effects of simvastatin on the function of dendritic cells in patients with rheumatic arthritis.

The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs. A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups: the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S). Twenty healthy individuals served as control. The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs. The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry. And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR). The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA. Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected. The relationship between the expression of CD86 and the blood CRP level was also investigated. The results showed that, as compared with the control group, the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients. T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2, IL-17, TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10). The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R. The CD86 expression was positively correlated with hs-CRP. It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA. Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP, indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exerts its effect in treating RA.

Effect of technetium-99 conjugated with methylene diphosphonate on IgM-RF, IgG-RF and IgA-RF.

To explore the effect of technetium-99 conjugated with methylene diphosphonate (99 TcMDP) on IgM-RF, IgG-RF and IgA-RF (RFs), 47 cases were selected for study, including 33 patients with rheumatoid arthritis (RA) and 15 patients with joint pain/arthritis. After 99Tc-MDP for drips model being given to the patients by intravenous drip 0.2 g daily for 5 days, the injection A and B models of 99Tc-MDP were used to the patients by intravenous injection one set daily for 10 days, that was one course of treatment. The next course started after 10 days. Each case used it from 2 to 4 courses of treatment. The RFs in serum were determined by the method of enzyme-linked immunoabsorption assay (ELISA) before and after 2 and 4 courses of treatment. In the patients with RA, the concentrations of IgM-RF were 296.2 +/- 108.4 IU/ml, 189.5 +/- 92.3 IU/ml and 107.8 +/- 72.5 IU/ml; the concentrations of IgG-RF were 325.6 +/- 126.2 IU/ml, 209.7 +/- 98.2 IU/ml and 160.2 +/- 80.8 IU/ml; the concentrations of IgA-RF were 330.4 +/- 136.3 IU/ml, 210.7 +/- 89.2 IU/ml and 148.8 +/- 72.2 IU/ml before and after 2 and 4 courses of treatment, respectively. The concentrations of the above RFs were significantly lower after 2 and 4 courses than those before treatment (P < 0.05 and P < 0.01). There was no significant difference in RFs concentrations in the patients with joint pain/arthritis before and after use of 99Tc-MDP. In the patients with positive RFs before treatment, the RFs concentrations were decreased significantly after 2 and 4 courses of treatment (P < 0.05 and P < 0.01). There was no obvious change of RFs concentrations in the patients with negative RFs after treatment of 99Tc-MDP. It was concluded that 99 Tc-MDP could obviously reduce the abnormally high concentrations of RFs, but not influence the normal RFs, which indicated that 99Tc-MDP has an important effect on controlling the activities of RA.

Relationship between glucocorticoid-induced osteoporosis and vitamin D receptor genotypes.

By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay, the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD) in the patients receiving long-term glucocorticoid therapy was studied. The clinical data and blood of 71 patients with rheumatosis who received long-term glucocorticoid therapy were collected. BMD was measured by dual-energy X-ray absorptimometry. VDR gene fragment (about 185 bp) was amplified by PCR from the extracted genomic DNA, then digested with restriction endonuclease Bsm I. The genotypes were evaluated based on the fragment length following endonuclease digestion and the association between genotypes and BMD or Z-score values was analyzed. Among the 71 cases, the detected genotypes were Bb and bb with the distribution frequency being 11.3% and 88.7% respectively. The distribution frequency of the alleles was in agreement with the Hardy-Weinberg equilibrium. There was no significant difference between the two genotypes in age, gender, body mass index (BMI), disease duration, disease types, time of glucocorticoid administration and cumulative dosage (P > 0.05). Osteoporosis rate of the patients with Bb or bb genotype was 37.5% and 33.3% respectively, with the difference being not significant (chi 2 = 0.05, P = 0.8). The BMD and Z-score values at lumbar spine and femur in two genotypes were not similar, but the difference had no significant (P > 0.05). The distribution frequency of bb type of VDR genotypes in Han populations of China was more prevalent, followed by Bb and bb types in turn. In the patients receiving long-term glucocorticoid therapy, there was no significant difference in BMD between Bb and bb genotypes. The data suggest that the VDR genotypes may not be means of identifying patients at greater risk of glucocorticoid-induced osteoporosis, which await to be further confirmed by a large sample size.