Role of lentivirus-mediated overexpression of SOCS3 in proliferation and apoptosis of fibroblasts-like synoviocytes in Lewis rats with adjuvant-induced rheumatoid arthritis.

The purpose of this study is to explore the effects of lentivirus-mediated overexpression of the SOCS3 gene on proliferation and apoptosis of fibroblasts-like synoviocytes (FLSs) in rheumatoid arthritis (RA). A total of 20 Lewis rats were randomly assigned into experimental and normal groups. Rats in the experimental group were modeled with adjuvant arthritisand the normal group was given no treatment. After culture for 28 days, rats in the experimental group were sacrificed, and the third-generation FLSs were collected and randomly allocated into SOCS3 group, control group, and blank group. MTT assay was used for detecting cell viability, flow cytometry was used for analysis ofcell apoptosis, and enzyme-linked immunosorbent assay (ELISA) was used to determine levels of inflammatory factors (interleukin [IL]-2, interferon [IFN-γ] and tumor necrosis factor [TNF-α]). MTT assay showed that the optical density of the SOCS3 group was significantly higher than that of the control and blank groups. Flow cytometry showed that the apoptosis rate of FLSs in the SOCS3 group was significantly lower than that in the control and blank groups. The results of ELISA assay showed that the levels of IL-2, IFN-γ and TNF-α in the SOCS3 group were higher than those in the control and blank groups. Our study demonstrates that over-expression of SOCS3 promotes proliferation and inhibits apoptosis of FLSs in RA.

Rutin Attenuates Oxidative Stress and Proinflammatory Cytokine Level in Adjuvant Induced Rheumatoid Arthritis via Inhibition of NF-κB.

The present study was intended to elucidate the effect of rutin, a flavonoid, on arthritis in complete Freund's adjuvant-induced arthritic rats. The present study showed that more pronounced effect has been observed in the case of 15 mg/kg dose of rutin, with significant reduction in paw diameter together with positive modulation of hematological parameters as compared to 2 other tested doses. A significant upsurge in the level of superoxide dismutase, glutathione peroxidase and glutathione were observed together with decrease in the level of malondialdehyde after treatment with rutin in a dose-dependent manner. Furthermore, the effect of rutin on the tumor necrosis factor-α and interleukin-1ß in arthritic rats showed does-dependent lowering of these cytokines with maximum benefit at 15 mg/kg dose and the level of both NF-κB p65 and NF-κBp65 (Ser536) has been significantly reduced in the presence of rutin. Histopathological examination showed that the inflammatory cells infiltration, synovial hyperplasia, pannus formation and cartilage and bone erosion had considerably improved on administration of rutin. In conclusion, our paper strongly demonstrated the protective effect of rutin against the rheumatoid arthritis involved via suppression of NF-κB p65 protein expression.

Association of Serum Interleukin-28B with Clinical Features, Laboratory Values and Radiographic Score in Rheumatoid Arthritis Patients.

BACKGROUND: Interleukin-28B (IL-28B) is a member of the interferon lambda family (also known as type III interferons), it has already been studied in many diseases, but it has almost never been studied in rheumatoid arthritis (RA). With this background, we determined the serum levels of IL-28B in RA patients and investigated its clinical significances. METHODS: IL-28B levels were measured by enzyme-linked immunosorbent assay (ELISA) in 80 RA patients and 80 healthy controls. Radiographs were scored for total Sharp score (TSS). RESULTS: Serum IL-28B levels were significantly lower in the RA than in the control (p = 0.02). Anticyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) were negatively correlated with serum IL-28B levels. There was no association between serum IL-28B levels and TSS at baseline, but there was a significant difference in change of IL-28B during 6 months follow up between progressors and non-progressors. The disease activity of RA patients decreased, but no difference was observed in serum IL-28B levels between before and after disease-modifying anti-rheumatic drugs (DMARDs) therapy. CONCLUSIONS: These findings indicated a role of IL-28B in RA and it may contribute to avoiding osteoclasia in RA patients.

Magnetic resonance imaging in early rheumatoid arthritis: a multicenter, prospective study.

To identify the magnetic resonance imaging (MRI) features of hands and wrists in early rheumatoid arthritis (RA). A total of 129 early arthritis patients (≤1 year) were enrolled in the study. At presentation, MRI of the hands was performed, with clinical and laboratory analyses. After a 1-year follow-up, clinical diagnosis of early RA or non-RA was confirmed by two rheumatologists. The characteristics of MRI variables at baseline in RA patients not fulfilling ACR 1987 criteria [RA-87(-)] were compared with those fulfilling ACR1987 criteria [RA-87(+)] and non-RA. In the 129 early arthritis patients, 90 were diagnosed with RA in a 1-year follow-up. There were 47.8 % (43/90) of the RA patients not fulfilling ACR 1987 criteria [RA-87(-)]. The scores of synovitis in RA-87(-) patients were similar with those in RA-87(+) [Synovitis score, 14.0 (IQR, 4.0-25.0) vs. 14.0 (IQR, 10.0-25.0), p > 0.05]. Compared with those in non-RA, RA-87(-) patients had higher synovitis scores and occurrence of synovitis in proximal interphalangeal (PIP) joints [synovitis score, 14.0 (IQR, 4.0-25.0) vs. 6.0 (IQR, 2.0-14.5), p = 0.046; occurrence of PIP synovitis: 53.5 vs. 27.3 %, p = 0.02]. There was no significant difference of bone marrow edema, bone erosion, and tenosynovitis between RA-87(-) and non-RA. Synovitis in PIP joints was independent predictor for RA-87(-) [OR, 3.1 (95 %CI 1.2-8.1)]. High synovitis scores and synovitis in PIP joints on MRI were important in early RA, especially those not fulfilling ACR 1987 criteria.

Efficacy and safety of weekly leflunomide for the treatment of early rheumatoid arthritis: a randomized, multi-center study.

AIM: The aim of this study was to determine the efficacy and safety of a weekly dose of leflunomide (50 mg/week) in early rheumatoid arthritis patients with mild or moderate disease activity. METHODS: The patients of early rheumatoid arthritis (ERA) with mild or moderate disease activity were randomly selected for inclusion in this study and were assigned to either the treatment group (leflunomide 50 mg/week, LEF50) or the control group (leflunomide 10 mg/day, LEF10). All patients were treated for 24 weeks. Clinical efficacy was assessed using the disease activity score in 28 joints (DAS28) - erythrocyte sedimentation rate (ESR) and European League Against Rheumatism (EULAR) response. A Chi-squared test, Fisher's exact-test and paired t-tests were used to analyze the data. RESULTS: A total of 244 patients who met the inclusion criteria and received at least one medicine dose were analyzed. At the baseline, the DAS28 (ESR) of the ERA patients were 4.41 ± 0.69 in LEF 50 group and 4.52 ± 0.64 in LEF 10 group, respectively. At week 24, the DAS28 (ESR) in two groups ( 2.94 ± 1.10 and 3.02 ± 1.14 ) were significant decreased compare with the baseline, respectively (P<0.01). There was no significant difference in DAS28 (ESR) between the LEF50 and LEF10 groups at week 24. (P > 0.05). At weeks 8, 12 and 24, the EULAR response (good responses + moderate responses) were 47.6%, 58.7% and 59.5%, in the LEF50 group and 43.2%, 49.1% and 53.4% in the LEF10 group, respectively. There was no significant different of EULAR response rates in the two groups at week 8, 12, and 24, respectively (P>0.05). There was no serious adverse events during the study. CONCLUSION: A weekly dose of 50 mg leflunomide showed similar benefits to a daily dose of 10 mg leflunomide for the treatment of mild-to-moderate early rheumatoid arthritis.

Low-molecular-weight adiponectin is more closely associated with disease activity of rheumatoid arthritis than other adiponectin multimeric forms.

Adiponectin is divided into high-molecular-weight (HMW), medium-molecular-weight (MMW), and low-molecular-weight (LMW) forms. These forms differ not only in the number of adiponectin molecules but also in their biological activity. There are conflicting findings regarding the role of adiponectin in rheumatoid arthritis (RA). Moreover, few reports have described the relationships between serum adiponectin multimers levels and RA. Therefore, we examined the association of total adiponectin and its multimers with RA. Two study groups were examined: 180 recently diagnosed untreated RA patients with disease duration less than 1 year (RA group) and 160 age- and sex-matched control subjects (control group). RA-related factors, blood pressure, body mass index, glucose, complete lipid profile, and adiponectin multimers were measured. The levels of total adiponectin and each multimer of adiponectin were significantly lower in the RA than in the control (P < 0.01). Serum levels of total, HMW, MMW, and LMW were positively correlated with triglycerides levels and negatively correlated with the Disease Activity Score for 28 joints (DAS28). Multivariate regression analysis showed that total, HMW, and MMW adiponectin were independently associated with serum triglycerides level. LMW adiponectin was independently correlated with serum triglycerides level and DAS28. The decreased LMW adiponectin levels may be associated with disease activity of RA.

A randomized, double-blind, and placebo-controlled multicenter clinical trial of a novel cytotoxic T-lymphocyte antigen-4 fusion protein, Leining, in Chinese active rheumatoid arthritis patients with an inadequate response to methotrexate.

To assess the clinical efficacy as well as safety profiles of Leining, a novel cytotoxic T-lymphocyte antigen-4 fusion protein, versus placebo in the treatment of Chinese active rheumatoid arthritis (RA) patients with an inadequate clinical response to methotrexate (MTX). In this 24-week, randomized, double-blind, placebo-controlled multicenter study, a total of 440 Chinese patients with active RA with an inadequate response to MTX were randomly assigned to receive Leining (10 mg/kg) or placebo. Clinical response was assessed using the American College of Rheumatology 20 % improvement criteria ACR20, ACR50, and ACR70, with ACR20 as the primary major endpoints. Disease activity scores in 28 joints with erythrocyte sedimentation rate assessment (DAS28-ESR) were used to evaluate disease activity. After 24 weeks of treatment, significantly more patients in Leining group achieved ACR20 response than those in placebo group (70.61 vs. 46.36 %; p < 0.001). Similarly, ACR50 and ACR70 responses of Leining group were significantly higher than those of placebo group (40.30 vs. 22.73 %; p < 0.001 and 16.67 vs. 7.27 %; p < 0.05, respectively). DAS28-ESR in Leining group was significantly reduced compared to that in placebo group, with greater clinically meaningful (>1.2 unit) improvement (54.85 vs. 29.09 %, p < 0.05). Both the rates of remission (DAS28-ESR < 2.6) and low disease activity (DAS28-ESR < 3.2) were greater in the Leining group than those in the placebo group (12.42 vs. 2.73 %; p < 0.05 and 15.45 vs. 2.73 %; p < 0.05 respectively). The overall incidence of adverse events was similar in both Leining and placebo groups. No neutralizing antibodies were detected. Leining demonstrated clinically meaningful efficacy compared with placebo in Chinese patients with active RA despite MTX therapy. Administration of Leining in combination with MTX for 24 weeks was well tolerated.

Determinants of brachial-ankle pulse wave velocity in Chinese patients with rheumatoid arthritis.

OBJECTIVE: To investigate the relationship between Brachial-ankle pulse wave velocity (baPWV), and its associated risk factors in Chinese patients with RA. METHODS: 138 Chinese RA patients and 150 healthy subjects were included. baPWV of all the participants was measured. RA related factors were determined, as well as traditional cardiovascular risk factors. RESULTS: baPWV was significant higher in RA group (1705.44 ± 429.20 cm/s) compared to the healthy control group (1386.23 ± 411.09 cm/s) (P < 0.001). Compared with low baPWV group, high baPWV group patients were significantly older (P = 0.008) and taller (P = 0.033). Serum cholesterol (P = 0.035), triglycerides (P = 0.004), and LDL level (P = 0.006) were significantly higher in high baPWV group patients compared with low baPWV group patients. The baPWV of RA patients was positively correlated with age (r = 0.439, P < 0.001), and serum cholesterol level (r = 0.231, P = 0.035), serum triglycerides level (r = 0.293, P < 0.001), serum LDL level (r = 0.323, P = 0.003). Meanwhile, baPWV negatively correlated with the height of RA patients (r = -0.253, P = 0.043). Multivariate regression analysis showed that baPWV of RA group was independently associated with age and serum triglycerides level. CONCLUSIONS: The old age and high level of serum triglycerides may be the major determinants of arterial stiffness in Chinese RA patients.

[Evaluation of MRI in the diagnosis of rheumatoid arthritis].

OBJECTIVE: to study the features of rheumatoid arthritis (RA) on MRI of hands and wrists and compare MRI with clinical manifestations and laboratory tests of RA. METHODS: a total of 25 patients fulfilling the 2009 ACR/EULAR RA criteria were enrolled. MRI and plain films of hands and wrists and clinical data of swollen joints, tender joints, visual scale (VAS) score, DAS28 score, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), RF classification, anti-cyclic citrullinated peptide antibodies (anti-CCP antibodies) were obtained simultaneously. RESULTS: MRI revealed pathologic findings on the wrist and hand joints in all diagnosed RA patients. VAS had a positive correlation with bone marrow edema(r = 0.562, P = 0.003). Although the disease duration was less or more than 1 year, the difference of bone erosion had statistical significance between anti-CCP antibody-positive group and anti-CCP antibody negative group (all P = 0.000). The serum concentration of RF-IgA had a positive correlation with bone marrow edema (r = 0.561, P = 0.041). The synovitis score of MRI of RA was higher in the RF-IgG positive group than that in the RF-IgG negative group (P = 0.035). There was significant difference in MRI synovitis between the RF-IgG or RF-IgM positive and negative groups of patients with a disease course of under 1 year (P = 0.015, P = 0.007). The serum CRP level had a positive correlation with arthroderma (r = 0.457, P = 0.022). CONCLUSION: MRI is proved to be a valuable examination for an early diagnosis and assessment of RA.

[Significance of citrullinated collagen type II and its antibodies in rheumatoid arthritis].

OBJECTIVE: To investigate the significance of citrullinated collagen type II and its antibodies in the pathogenesis and diagnosis of rheumatoid arthritis (RA). METHODS: Serum samples were obtained from 175 patients with RA, 112 patients with systemic lupus erythematosus (SLE), 37 patients with osteoarthritis (OA), and 160 healthy controls. Arginine residues of bovine collagen type II (bCII) were converted to citrulline residues by peptidylarginine deiminase (PAD). The presence of antibodies against citullinated bCII (Cit-bCII) and bCII, a substrate protein of PAD, were examined by using enzyme-linked immunosorbent assay (ELISA) and Western blotting. The levels of anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) in the above patients were detected. RESULTS: The positive rate of anti-CitbCII antibodies of the RA patients was 50.3% (88/175), significantly higher than those of the SLE patients (17.9%, 20/112), OA patients (18.9%, 7/37), and healthy controls (2.5%, 4/160). The positive rate of anti-b of the RA patients was 33.7% (59/175), significantly lower than that of the CII antibodies. The levels of anti-CitbCII and anti-bCII antibodies were not statistically different from SLE and OA patients. There was a close correlation between anti-CitbCII and anti-CCP antibodies. Spearman correlation analysis showed that anti-CitbCII antibodies were positively correlated with anti-CCP antibodies, and CRP, ESR, RF, X ray imaging, course of disease, and age were not associated with anti-CitbCII antibodies. CONCLUSION: Anti-citrullinated bCII antibody is relatively RA-specific. Citrullination appears to be important in RA.