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Objectives: We aimed to evaluate the effects of age on clinical characteristics and outcomes in biologic or targeted synthetic disease-modifying antirheumatic drug (b/tsDMARD)-naïve patients with rheumatoid arthritis (RA). Methods: We analysed the cases of 234 Japanese b/tsDMARD-naïve RA patients who underwent b/tsDMARD treatment in a multicentre ultrasound prospective observational cohort. We compared the clinical characteristics at baseline and outcomes at 12 months between those aged ≥60 years and those <60 years. Results: Compared to the <60-year-old group (n = 78), the ≥60-year-old group (n = 156) had higher inflammatory marker values and ultrasound combined scores, especially wrist joints, at baseline. Age at baseline positively correlated significantly with the ultrasound scores at baseline; however, age was not a significant variable by the multiple regression analysis. The patients treated with different MOAs in the ≥60-year-old group had comparable outcomes and multiple regression analysis revealed that mechanism of action (MOA) was not a significant contributor to the Clinical Disease Activity Index at 12 months. Conclusions: RA patients with advanced age demonstrated distinctive clinical characteristics. The MOAs were not associated with clinical outcomes and ultrasound outcomes in RA patients with advanced age. [ABSTRACT FROM AUTHOR]

Objective: Glucocorticoids are effective in treating rheumatoid arthritis (RA) when used appropriately considering the balance of the risks and benefits, especially at low doses. We aimed to evaluate the response of biologic and targeted synthetic disease‐modifying antirheumatic drugs (b/tsDMARDs) in patients having already been treated with glucocorticoids. Methods: We reviewed RA patients treated with b/tsDMARDs in a prospective multicenter ultrasound cohort study. We compared the differences in the clinical characteristics at baseline and outcomes at 12 months between the two groups having been treated with and without glucocorticoids at baseline. The differences in the clinical characteristics and the treatments were balanced by the inverse probability weighting (IPW) with the propensity score. Results: Of 307 patients with RA, 160 patients were treated with glucocorticoids at baseline. The median dose of glucocorticoids was equivalent to 5.0 mg/day of prednisolone. Significant differences were in age and concomitant methotrexate use, composite measures for the disease activity, and the ultrasound grayscale score at baseline. Patients treated with glucocorticoids had less frequent remissions defined by composite measures and ultrasound findings than those treated without glucocorticoids. These significant differences in the achievement of remissions remained robust even after adjusting differences in the clinical characteristics and the treatments between the two groups by IPW. Conclusion: RA patients treated with glucocorticoids had a higher disease activity at baseline and a poorer response to treatments with b/tsDMARDs than those without glucocorticoids. The states of patients requiring glucocorticoids might be associated with the poor response to the b/tsDMARDs. [ABSTRACT FROM AUTHOR]

Objectives: The link between the HLA‐DRB1 locus and the risk of rheumatoid arthritis (RA) shown in genome‐wide association studies strengthens the shared epitope (SE) hypothesis. We aimed to assess the impact of the double dose of the SE (double SE) on RA and explore its clinical associations, including the response to abatacept. Methods: We evaluated RA patients treated with csDMARDs or abatacept for HLA‐DRB1 typing, clinical characteristics at baseline, and disease activity and ultrasound findings over 12 months. Results: Patients with the double SE (n = 12) had significantly higher anti‐citrullinated protein antibody (ACPA) titers, higher total grayscale (GS) score, and power Doppler (PD) score at baseline than patients without the double SE. Patients with the double SE exhibited reduced rates of SDAI remission and pronounced improvements in multiple disease activity between baseline and 12 months, including SDAI, CDAI, total GS score, and total PD score. When focusing on abatacept‐treated patients, the decreases in SDAI, CDAI, and total PD score between baseline and 12 months were significantly larger in patients with the double SE. Conclusions: Patients with the double SE exhibited distinct characteristics, increased disease activity, and improved response to abatacept treatment. [ABSTRACT FROM AUTHOR]

Remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE), a rheumatic disease affecting the elderly, responds well to corticosteroids; however, our RS3PE patients' corticosteroid therapy is longer than expected. Elderly-onset rheumatoid arthritis (EORA) patients are reported to be at a significantly increased risk for steroid-related side effects including cardiovascular diseases (CVDs). To clarify the complications during a 1-year follow-up in corticosteroid-treated RS3PE patients compared to EORA patients. We retrospectively analyzed the records of 47 RS3PE patients (28 men, 19 women, age 78.4 ± 7.5 years) and 46 EORA patients (10 men, 36 women; 77.0 ± 6.8 yrs) to compare the complications over a 1-year follow-up. The RS3PE and EORA groups' average initial PSL doses were 16.5 ± 7.2 mg/day and 7.3 ± 4.6 mg/day, respectively. During the 1-year follow-up after treatment, there was no significant increase in CVDs in both groups. However, infections occurred in nine RS3PE patients, which is a significantly higher incidence compared to the EORA patients with infections (n = 3). The initial PSL dose was the independent variable associated with the incidence of infection. Infections were significantly increased during elderly RS3PE patients' steroid therapy. The initial corticosteroid dose was an infection-risk factor. Infections are increased during steroid therapy in elderly patients with RS3PE syndrome. The initial dose of corticosteroids was one of the risk factors for infections. [ABSTRACT FROM AUTHOR]

Objectives It has been suggested that patients with RA are more likely to suffer from depression. Therefore, this study identified the factors associated with depressive states in female RA patients to inform future patient care. Methods A self-assessment questionnaire was administered to 150 female RA patients aged ≥20 years regarding their satisfaction with disease activity, pain (measured using a visual analogue scale), self-rated depression scale (SDS), stress content (illness, work, family, difficulty in daily life, appearance, treatment and other), confidence in stress management and satisfaction (treatment effect, health status and relationships with health-care professionals). The factors related to depression and the presence of depressive tendencies were investigated. Results Data from 145 patients were analysed. Eighteen patients (12.4%) showed depressive tendencies according to their SDS scores. Among these patients, SDS scores were positively correlated with disease activity and with scores on the modified HAQ, visual analogue scale for pain, and stress content. The SDS score was also negatively correlated with patients' confidence in stress management and health status satisfaction. Conclusion Female RA patients had family problems and various stressors in their daily lives. Nurses need to conduct regular mental health assessments to monitor their self-management status and support them to improve their confidence and satisfaction in coping. To achieve this, it is important for health-care teams involving various health-care professionals to collaborate and cooperate. [ABSTRACT FROM AUTHOR]

To compare therapeutic efficacy of tumour necrosis factor inhibitor (TNFi) cyclers and non-TNFi switchers in patients with rheumatoid arthritis (RA) having inadequate response to previous TNFis (TNF-IR patients) using composite measures including imaging assessment with power Doppler ultrasonography (PDUS). Patients with RA who had inadequate response to one or more previous TNFi agents with moderate or higher disease activity were enrolled. The outcomes of 56 TNF-IR patients were analysed. Patients were divided into 19 TNFi cyclers and 37 non-TNFi switchers (16 abatacept [ABT] and 21 tocilizumab [TCZ] switchers). Retention ratio at 6 months was significantly higher in non-TNFi switchers than in TNFi cyclers (p <.05). Although there was no significant difference, non-TNFi switchers tended to have a larger decrease than TNFi cyclers in efficacy indicators based on clinical disease activity index and PDUS. Multivariate logistic regression analysis identified a following independent factor associated with both EULAR good response and retention of a biologic agent: non-TNFi switch (p <.05 for both). Non-TNFi switchers were shown to have significantly higher percentage of EULAR good response and higher retention than TNFi cyclers. A non-TNFi biologic agent may hence be a preferential next-line treatment for TNF-IR patients. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively analyze the differences in musculoskeletal ultrasound (MSUS) findings to distinguish patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome and patients with elderly-onset rheumatoid arthritis (EORA). Methods: We consecutively recruited patients with RS3PE syndrome (n = 7) and EORA (n = 22) who underwent pre-treatment MSUS of both hands. Synovial hypertrophy and vascularity of articular synovitis and those of tenosynovitis of the digital flexor tendons and the carpal extensor tendon were evaluated by gray-scale and power Doppler, respectively on a semi-quantitative scale (0–3). The presence/absence of intra-articular synovial effusion, bone erosion, peritendinitis of the digital extensor tendon, and subcutaneous edema were noted. Results: Compared to the EORA group, mild articular synovitis was observed more extensively, and the frequency of intra-articular synovial effusion was significantly higher in the RS3PE syndrome group. Severe articular synovial hypertrophy was more frequent in the EORA group compared to the RS3PE syndrome group, and bone erosion was observed in some EORA cases. Tenosynovitis of the digital flexor tendon was more frequent and severe in the RS3PE syndrome group compared to the EORA group. Although the frequency and severity of tenosynovitis of the carpal extensor tendon were similar in the two groups, digital extensor tendon peritendinitis was more frequent in the RS3PE syndrome group. Conclusion: To distinguish patients with RS3PE syndrome from those with EORA, it is important to evaluate not only intra-articular lesions but also extra-articular lesions by MSUS. Key Points • We retrospectively compared MSUS findings of RS3PE syndrome and EORA in detail. • MSUS revealed extensive intra- and extra-articular inflammation in patients with RS3PE syndrome • Evaluating not only intra-articular lesions but also extra-articular lesions helps distinguish RS3PE syndrome and EORA [ABSTRACT FROM AUTHOR]

Aim: We conducted this retrospective study to identify objective and comprehensive diagnostic criteria for early‐stage rheumatoid arthritis (RA) that are based on ultrasound (US) and serologic findings. Method: From August 2014 to May 2016, we recruited 216 consecutive patients at Hospital 1 and 223 consecutive patients at Hospital 2 who were suspected to have RA and underwent US of bilateral hands. In the US of bilateral hands from 22 sites, the findings obtained by grayscale and power Doppler (PD) assessments were each graded on a semi‐quantitative scale from 0 to 3. We also examined the assessment of the novel outcome measures in rheumatology (OMERACT)‐European League Against Rheumatism (EULAR) combined power Doppler ultrasound score (ie the cPD score) and the Global OMERACT‐EULAR Synovitis Score. We used the US findings and the combination of US and serologic findings to evaluate the diagnostic performance of these modalities. Results: Seventy patients (32.4%) at Hospital 1 and 59 patients (26.5%) at Hospital 2 were diagnosed as having RA. The best‐balanced diagnostic performance at each hospital was achieved using a combination, such as (1) the presence of PD grade ≥2 articular synovitis or (2) the presence of PD grade ≥1 articular synovitis and serologic positivity, as well as by using (1) the presence of cPD grade = 3 or (2) a cPD grade ≥2 and serologic positivity. Conclusion: The combination of a PD assessment or the cPD score with the measurement of autoantibodies of rheumatoid factor and/or anti‐cyclic citrullinated peptide antibodies can accurately identify patients with early‐stage RA. [ABSTRACT FROM AUTHOR]

To assess the efficacy and safety of switching to infliximab (IFX) from other biological disease-modifying anti-rheumatic drugs (bDMARDs) among Japanese patients with rheumatoid arthritis (RA) in daily practice. We examined 24 consecutive RA patients who had not achieved low disease activity (LDA) as the disease activity score-28 for rheumatoid arthritis with erythrocyte sedimentation rate (DAS28-ESR) despite previous bDMARD therapy in this cohort study. We attempted to determine predictive variables that are associated with achieving DAS28-ESR LDA at 22 weeks post-IFX introduction, by performing univariate analysis. The median DAS28-ESR at baseline was 5.41. Sixteen patients (66.7%) had been treated with a tumor necrosis factor inhibitor (TNF-i), and the other eight patients (33.3%) received a non-TNF-i (abatacept or tocilizumab). Nine patients (37.5%) achieved LDA or remission at 22 weeks. Univariate analyses showed that the variable to predict LDA achievement at 22 weeks was tender joints (>8 counts) at baseline (adjusted odds ratio, 0.10; 95% confidence interval, 0.01-0.63; p = .02). Nine adverse events were observed during the study period, and infection requiring hospitalization was observed in one patient. Switching to IFX is effective to achieve LDA or remission for RA patients refractory to bDMARDs. [ABSTRACT FROM AUTHOR]

Objectives: We investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC) differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA). Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro. Results: Forty RA patients and 20 healthy donors were included. Twenty-two patients (55%) were anticitrullinated protein antibody (ACPA) positive. The median M1/M2 ratio was 0.59 (0.31-1.11, interquartile range). There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001). The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028) and significantly greater numbers of OCs in vitro (p = 0.005) than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes) had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes. Conclusion: M1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the efficacy and safety of tofacitinib in patients with rheumatoid arthritis (RA) in a real-world setting. Methods: Seventy consecutive patients, for whom tofacitinib was initiated between November 2013 and May 2016, were enrolled. All patients fulfilled the 2010 ACR/EULAR classification criteria for RA. All patients received 5 mg of tofacitinib twice daily and were followed for 24 weeks. Clinical disease activity indicated by disease activity score (DAS)28-ESR, the simplified disease activity index, and the clinical disease activity index as well as adverse events (AEs) were evaluated. Statistical analysis was performed to determine which baseline variables influenced the efficacy of tofacitinib at 24 weeks. Results: Fifty-eight patients (82.9%) continued tofacitinib at 24 weeks. Clinical disease activity rapidly and significantly decreased, and this efficacy continued throughout the 24 weeks: i.e., DAS28-ESR decreased from 5.04 ± 1.33 at baseline to 3.83 ± 1.11 at 4 weeks and 3.53 ± 1.17 at 24 weeks (P<0.0001, vs. baseline). 15 AEs including 5 herpes zoster infection occurred during tofacitinib treatment. The efficacy of tofacitinib was not changed in patients without concomitant use of methotrexate (MTX) or patients whose treatment with tocilizumab (TCZ) failed. Multivariable logistic analysis showed that the number of biologic DMARDs (bDMARDs) previously used was independently associated with achievement of DAS-low disease activity. Conclusions: Our present study suggests that tofacitinib is effective in real-world settings even without concomitant MTX use or after switching from TCZ. Our results also suggest that its efficacy diminishes if started after use of multiple bDMARDs. [ABSTRACT FROM AUTHOR]

Objectives The risk factors of adverse events during a number of currently used treatments for rheumatoid arthritis ( RA) in elderly patients were examined. Methods A retrospective observational study was conducted for 300 elderly RA patients registered in December 2009 at Sasebo Chuo Hospital, Japan, and the adverse events during the treatments for RA were assessed. Results The average age of the patients was 74.3 ± 5.8 years. The Steinbrocker stage was IV in almost one-half of the patients. Methotrexate ( MTX) was used in 54.0% of patients and biologics in 23.0% of patients. Adverse events occurred in 103 patients (34.3%). The most common adverse events were infections (46.6%), including pneumonia (21.4%). Multiple logistic analyses revealed that the factors significantly related to infection were advanced Steinbrocker stage and the existence of respiratory diseases, and that of pneumonia was the existence of diabetes mellitus ( DM). Conclusions The elderly RA patients with advanced stage, respiratory diseases or DM should be monitored for infections, including pneumonia, carefully during treatment. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to explore whether assessment of synovial inflammation by ultrasonography correlates with MRI-proven osteitis in patients with RA.Methods. Thirty RA patients who fulfilled 2010 RA classification criteria and were naive to DMARDs, including biologics and glucocorticoids, were consecutively enrolled in this study. Grey scale (GS) and power Doppler (PD) images of articular synovitis and bone erosion in both wrist and MCP joints were evaluated by the method proposed by the European League Against Rheumatism. MRI-proven osteitis of the identical sites was also evaluated within 3 days using the RA MRI scoring system (RAMRIS). The Cochran–Armitage test and Spearman’s correlation coefficient were used to investigate the correlation of each US finding with MRI-proven osteitis.Results. MRI-proven osteitis was found in 8.3% of MCP joints and 48.3% of wrist joints. Its prevalence was increased in the joints where the GS or PD grade of articular synovitis was 2 or 3. In addition, MRI-proven osteitis was found preferentially in the joints positive for bone erosion on US. A clear correlation was demonstrated between the GS or PD grade of articular synovitis or the presence of US bone erosion and RAMRIS osteitis score in both MCP joints and wrist joints.Conclusion. Our data indicate that joint injury assessed by US correlates with MRI-proven osteitis in patients with RA. [ABSTRACT FROM PUBLISHER]

Objective. The aim of this study was to investigate the characteristics of power Doppler (PD) subclinical synovitis in patients with RA who achieve clinical remission free from physical synovitis.Methods. Twenty-nine RA patients were consecutively enrolled. All of the patients had achieved clinical remission [simplified disease activity index (SDAI) 3.3] for at least 6 months at the musculoskeletal ultrasound (MSKUS) examination. Additionally, none of the patients exhibited tender joints at 68 sites or swollen joints at 66 sites. MSKUS of bilateral wrist and finger joints, including the first to fifth MCP joints, the first IP joint and the second to fifth PIP joints, was performed and the findings obtained by grey scale (GS) and PD were graded on a semi-quantitative scale from 0 to 3.Results. The median disease duration upon the introduction of DMARDs was 3 months and that at MSKUS examination was 21 months. The percentages of patients with PD synovitis in at least one joint were PD grade 1, 58.6%; PD grade 2, 31.0% and PD grade 3, 6.9%. The use of biological agents was low in patients with PD synovitis grade 2 (P < 0.05). The presence of US bone erosion was high by patient (P < 0.05) and by joint (P < 0.0001) with PD synovitis as compared with those without PD synovitis. However, no correlations were found between PD synovitis measures and serum biomarkers, including angiogenesis factors.Conclusion. PD subclinical synovitis correlates with several clinical characteristics, whereas conventional serum biomarkers are not useful for indicating the presence of subclinical PD synovitis. [ABSTRACT FROM AUTHOR]

Objective: To identify the value of magnetic resonance imaging (MRI)-proven bone edema in patients with very early rheumatoid arthritis (RA). Methods: All of the 13 patients included in the study were positive at entry for MRI-proven bone edema of the wrist and finger joints and anti-cyclic citrullinated peptide antibodies or IgM-rheumatoid factor. A tight control approach was applied for 12 months. Plain MRI and radiographs of both wrist and finger joints were examined every 6 months. MRI was scored by the RA MRI scoring (RAMRIS) technique and plain radiographs were scored using the Genant-modified Sharp score. Variables that were correlated with plain radiographic changes at 12 months were examined. Results: Simplified disease activity index (SDAI) remission was achieved in 7 patients, and a significant reduction in the RAMRIS bone edema score, which declined to <33 % as compared with the baseline, was achieved in 8 out of 13 patients. Four patients showed plain radiographic progression while 9 patients did not. Significant reductions in the RAMRIS bone edema score ( p = 0.007) and the time-integrated SDAI ( p = 0.031) were the variables involved in plain radiographic progression. Conclusions: Improvement in bone edema may be associated with protection against structural damage in very early RA patients managed using the tight control approach. [ABSTRACT FROM AUTHOR]

Objective: To explore whether synovitis and bone lesions in the wrists and finger joints visualized by plain magnetic resonance imaging (MRI)-based findings correspond exactly or not to those judged by gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI-based findings. Methods: Magnetic resonance imaging of the wrists and finger joints of both hands were examined in 51 early-stage rheumatoid arthritis (RA) patients whose median disease duration from the onset of articular manifestations to entry was 5 months, by both plain (T1 and short-time inversion recovery images) and Gd-DTPA-enhanced MRI (post-contrast fat-suppressed T1-weighted images) simultaneously. We focused on 15 sites per hand, to examine the presence of synovitis and bone lesions (bone edema and bone erosion). Gd-DTPA-enhanced MRI-based findings were considered 'true' lesions, and we evaluated the accuracy of plain MRI-based findings in comparison to Gd-DTPA-enhanced MRI-based findings. Results: Synovitis, judged by plain MRI-based findings, appeared as false-positive at pretty frequency; thus, the specificity, positive predictive value and accuracy of the findings were low. The rate of enhancement (E-rate) in false-positive synovitis sites was significantly low compared with true-positive synovitis sites where Gd-DTPA enhancement appears. In contrast to synovitis, the false-positivity of bone lesions, judged by plain MRI-based findings, was very low compared with Gd-DTPA-enhanced MRI-based findings. Conclusion: Synovitis judged by plain MRI-based findings is sometimes considered false-positive especially in sites where synovitis is mild. However, plain MRI is effective in identifying bone lesions in the wrist and finger joints in early-stage RA. [ABSTRACT FROM AUTHOR]

We aimed to identify whether drug-free remission could be achieved in patients with very early rheumatoid arthritis (RA) with poor prognosis factors by treatment with synthetic disease-modifying antirheumatic drugs (DMARDs). Thirteen patients with very early RA, whose disease was considered to have highly erosive potential, were included. Magnetic resonance imaging (MRI)-proven bone edema and autoantibodies were determined in these patients. A treat-to-target strategy initiated with synthetic DMARDs was employed for 12 months. If the patients achieved simplified disease activity index (SDAI) remission along with a reduction of the RA MRI scoring bone edema score to <33% as compared with baseline at 12 months, DMARD treatment was stopped and the clinical status was further observed for the following 12 months. Synthetic DMARDs were stopped at 12 months in 5 patients. One of the 5 was lost to follow-up because of sustaining an injury that required orthopedic surgery. Three of the remaining 4 patients showed continued SDAI remission that was DMARD-free without any evidence of radiographic progression for the following 12 months. Although this was a small clinical trial, we have shown-for the first time-that true remission of very early RA with poor prognosis factors can be achieved by treatment with synthetic DMARDs. [ABSTRACT FROM AUTHOR]

Objective. We evaluated the significance of the power Doppler ultrasonography (PDUS) score by comparing it with serum biomarkers and clinical disease activity.Methods. We measured the PDUS scores of 24 synovial sites in 12 joints in 22 RA patients. For convenience, the PDUS scores of six synovial sites in six joints were also examined. Each joint was scored for a power Doppler (PD) signal on a scale from 0 to 3. The PDUS scores are the sums of the PD signal scores for the 24 synovial sites or the 6 synovial sites. On the same day, serum variables as well as clinical disease activity were evaluated.Results. The PDUS scores from the 24 joint sites were significantly positively correlated with DAS of 28 joints (DAS-28), simplified disease activity index (SDAI), clinical disease activity index (CDAI) and serum biomarkers including MMP-3, VEGF and tissue inhibitor of metalloproteinases-1 (TIMP-1). Accordingly, the PDUS scores from the six synovial sites greatly correlated with those from the 24 joint sites. Clinical disease activities as well as serum variables were also clearly correlated with the PDUS scores from the six synovial sites.Conclusion. The standard as well as the simplified PDUS scores well reflected clinical disease activity and serum variables, including angiogenic factors. Our data reaffirm the utility of ultrasonography for monitoring disease activity in patients with RA. [ABSTRACT FROM PUBLISHER]

To elucidate the characterization of peripheral natural killer (NK) cells in patients with rheumatoid arthritis (RA), we investigated the NK cell activity, the expression of NK cell activating receptors and intracellular molecules. The NK activity was analyzed in 27 RA patients, 22 primary Sjögren’s syndrome (SS) patients, and 15 healthy individuals using the 51Chrominium release assay. The expression of NK cell activating receptors (NKG2D, CD244, CD2, and CD16) and intracellular molecules (granzyme B, perforin, and TCR ζ chain) in CD3-CD56+ cells were characterized by flow cytometry. The serum cytokine levels (IL-6, TNFα, and IL-18) were measured using ELISA. Both the NK cell activity and the activity on a per-cell basis were observed to significantly decrease in the RA patients in comparison to the controls. The expression of NKG2D and CD244 also significantly decreased in both the RA and primary SS patients, whereas the significant decrease in the CD16 expression was only observed in the RA patients. The titer of the serum IL-6, TNFα, and IL-18 was significantly higher in the RA patients than in the controls. These data suggest that a low NK activity on a per-cell basis might therefore contribute to an impaired NK activity in the patients with RA. [ABSTRACT FROM AUTHOR]

Several clinical trials have demonstrated that leukocytapheresis (LCAP) is a safe and effective therapy for patients with refractory rheumatoid arthritis (RA). However, most of those reports were limited to short-term clinical observation. We have treated 11 RA patients with LCAP and observed them for 24 weeks after the final administration. The 11 cases included 3 diabetes patients, 2 patients with interstitial pneumonia, 1 patient with diffuse panbronchiolitis, and 1 patient with old pulmonary tuberculosis. Alternative therapies for all of these patients were considered difficult. Once-a-week LCAP administration was added for 5 weeks to the previous therapeutic regime in all patients, and the treatment efficacy was prospectively qualified. At 4 weeks after the final LCAP therapy, 8 of the 11 patients (73%) had achieved an American College of Rheumatology (ACR) 20% response, and 3 of the 11 (27%) had achieved both ACR 50% and ACR 70% responses. Although the efficacy decreased after the observation periods, an ACR 20% response was maintained in 5 patients (45%) at 24 weeks. Although only a limited number of patients were examined in this study, the results suggested that LCAP therapy will be beneficial to RA patients, including patients who cannot be treated with tumor necrosis factor inhibitors or conventional disease-modifying antirheumatic drugs. [ABSTRACT FROM AUTHOR]

We report the case of a 73-year-old woman who suffered from amyloidosis secondary to rheumatoid arthritis (RA) complicated with Graves' ophthalmopathy. She had goiter, diplopia, and exophthalmos with polyarthralgia. We diagnosed Graves' ophthalmopathy with thyroid-stimulating hormone (TSH)-receptor antibodies (TBII and TSAb). The amyloid deposit was detected in her stomach. The complication of Graves' ophthalmopathy in amyloidosis secondary to RA has rarely been reported. [ABSTRACT FROM AUTHOR]

We aimed to investigate the effect of methotrexate (MTX) on microRNA modulation in rheumatoid arthritis fibroblast-like synovial cells (RA-FLS). RA-FLS were treated with MTX for 48 h. We then performed miRNA array analysis to investigate differentially expressed miRNAs. Transfection with miR-877-3p precursor and inhibitor were used to investigate the functional role of miR-877-3p in RA-FLS. Gene ontology analysis was used to investigate the cellular processes involving miR-877-3p. The production of cytokines/chemokines was screened by multiplex cytokine/chemokine bead assay and confirmed by ELISA and quantitative real-time PCR. The migratory and proliferative activities of RA-FLS were analyzed by wound healing assay and MKI-67 expression. MTX treatment altered the expression of 13 miRNAs (seven were upregulated and six were downregulated). Among them, quantitative real-time PCR confirmed that miR-877-3p was upregulated in response to MTX (1.79 ± 0.46-fold, p < 0.05). The possible target genes of miR-877-3p in RA-FLS revealed by the microarray analysis were correlated with biological processes. The overexpression of miR-877-3p decreased the production of GM-CSF and CCL3, and the overexpression of miR-877-3p inhibited migratory and proliferative activity. MTX altered the miR-877-3p expression on RA-FLS, and this alteration of miR-877-3p attenuated the abundant production of cytokines/chemokines and proliferative property of RA-FLS. [ABSTRACT FROM AUTHOR]

Investigates the role of superantigen in rheumatoid arthritis (RA) by assaying the serum levels of staphylococcal enterotoxin B (SEB) antibodies. Use of an enzyme linked immunosorbent assay confirmed by Western blot analysis; Analysis of a variety of T cell receptor V beta repertoire using the reverse transcriptase polymerase chain reaction.

Akt is known to be activated in the rheumatoid synovial tissues. We examined here functional role of Akt during tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-mediated apoptosis in rheumatoid synovial cells. Rheumatoid synovial cells in vitro were rapidly committed to apoptosis in response to TRAIL in mitochondria-dependent manner whereas Akt and extracellular signal-regulated kinase (ERK) were also phosphorylated. TRAIL-mediated apoptosis in synovial cells was significantly increased through inactivation of Akt by LY294002, however, that process was not so changed by adding ERK inhibitor, PD98059. Platelet-derived growth factor (PDGF) clearly phosphorylated both Akt and ERK in synovial cells, and PDGF pretreatment markedly suppressed TRAIL-mediated synovial cell apoptosis. The use of not PD98059 but LY294002 abrogated PDGF-mediated inhibitory effect toward TRAIL-induced apoptosis in synovial cells. The above protective effect of Akt was confirmed by the use of short interfering RNA (siRNA)-directed inhibition of Akt. Our data suggest that Akt is an endogenous inhibitor during TRAIL-mediated synovial cell apoptotic pathway, which may explain that synovial cells in situ of the rheumatoid synovial tissues are resistant toward apoptotic cell death in spite of death receptor expression. [Copyright &y& Elsevier]

Abstract: Objective: The aim of this study was to evaluate whether serum COMP can estimate the therapeutic response of RA after 6 months of treatment with etanercept. Methods: Forty-five RA patients receiving 25mg of etanercept twice a week for 6 months were registered in this prospective observational study. Clinical response to the therapy was evaluated by DAS 28. Laboratory variables– COMP, CRP, ESR, IgM-RF, MMP-3, and anti-CCP Ab –were assessed at baseline and after 6 months of treatment. We assessed the correlations between serum COMP and other variables and whether serum COMP is associated with DAS28 remission. Results: Serum COMP correlated with DAS28-ESR (p <0.05, r =0.40) at baseline. At 6 months of etanercept treatment, 10 patients entered remission (DAS28-ESR<2.6) whereas the other 35 patients did not (DAS28-ESR>2.6). The decrement of serum COMP at 6 months was significant in the remission group (N =10) but not in the non-remission group (N =35). On the other hand, CRP, ESR and MMP-3 decreased at 6 months regardless of remission status. IgM-RF titer as well as anti-CCP Ab titer did not differ at 6 months. Conclusions: Serum COMP at baseline reflects clinical disease activity of RA. Serum COMP is a valuable serologic marker to identify the subset of RA patients achieving remission during treatment with etanercept. [ABSTRACT FROM AUTHOR]