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ID PMID Title PublicationDate abstract
27589701 Dimacrolide Sesquiterpene Pyridine Alkaloids from the Stems of Tripterygium regelii. 2016 Aug 29 Two new dimacrolide sesquiterpene pyridine alkaloids (DMSPAs), dimacroregelines A (1) and B (2), were isolated from the stems of Tripterygium regelii. The structures of both compounds were characterized by extensive 1D and 2D NMR spectroscopic analyses, as well as HRESIMS data. Compounds 1 and 2 are two rare DMSPAs possessing unique 2-(3'-carboxybutyl)-3-furanoic acid units forming the second macrocyclic ring, representing the first example of DMSPAs bearing an extra furan ring in their second macrocyclic ring system. Compound 2 showed inhibitory effects on the proliferation of human rheumatoid arthritis synovial fibroblast cell (MH7A) at a concentration of 20 μM.
27096429 Influenza and Pneumococcal Vaccination Uptake in Patients with Rheumatoid Arthritis Treate 2016 INTRODUCTION: Guidelines for the management of rheumatoid arthritis (RA) recommend using influenza and pneumococcal vaccinations to mitigate infection risk. The level of adherence to these guidelines is not well known in the UK. The aims of this study were to describe the uptake of influenza and pneumococcal vaccinations in patients with RA in the UK, to compare the characteristics of those vaccinated to those not vaccinated and to compare vaccination rates across regions of the UK. METHODS: A retrospective cohort study of adults diagnosed with incident RA and treated with non-biologic immunosuppressive therapy, using data from a large primary care database. For the influenza vaccination, patients were considered unvaccinated on 1st September each year and upon vaccination their status changed to vaccinated. For pneumococcal vaccination, patients were considered vaccinated after their first vaccination until the end of follow-up. Patients were stratified by age 65 at the start of follow-up, given differences in vaccination guidelines for the general population. RESULTS: Overall (N=15,724), 80% patients received at least one influenza vaccination, and 50% patients received a pneumococcal vaccination, during follow-up (mean 5.3 years). Of those aged below 65 years (N=9,969), 73% patients had received at least one influenza vaccination, and 43% patients received at least one pneumococcal vaccination. Of those aged over 65 years (N=5,755), 91% patients received at least one influenza vaccination, and 61% patients had received at least one pneumococcal vaccination. Those vaccinated were older, had more comorbidity and visited the GP more often. Regional differences in vaccination rates were seen with the highest rates in Northern Ireland, and the lowest rates in London. CONCLUSIONS: One in five patients received no influenza vaccinations and one in two patients received no pneumonia vaccine over five years of follow-up. There remains significant scope to improve uptake of vaccinations in patients with RA.
25684765 Prediction of clinical response after 1 year of infliximab therapy in rheumatoid arthritis 2015 Apr OBJECTIVE: To investigate the probability of clinical remission (REM) or low disease activity (LDA) after 1 year of infliximab (IFX) therapy based on disease activity at 3 months in patients with rheumatoid arthritis (RA). METHODS: Methotrexate-refractory patients with RA received 3 mg/kg of IFX at weeks 0, 2, and 6, followed by 3 mg/kg, 6 mg/kg, or 10 mg/kg every 8 weeks from Week 14 (W14) to Week 46. Correlation of disease activity at W14 with disease activity at W54 and probability of REM/LDA at W54 were analyzed in each dosing group. RESULTS: Disease activities at W14 were significantly correlated with both disease activity at W54 and probability of REM/LDA at W54 in patients continuing 3 mg/kg as well as in those receiving 6 mg/kg or 10 mg/kg therapy from W14. Results showed that, if approximate REM or LDA had not been achieved by W14, > 50% of patients continuing 3 mg/kg therapy would not be able to achieve REM or LDA at W54. However, even in patients with high or moderate disease activity at W14, dose escalation to 6 mg/kg or 10 mg/kg enabled many to achieve REM/LDA. CONCLUSION: Disease activity at W14 in standard-dose IFX therapy enabled the prediction of longterm clinical response at continued standard dose, as well as subsequent escalated-dose regimens. Disease activity at W14 was hypothesized to be an important index for IFX treatment strategy.
25963989 Tertiary Lymphoid Structures in Rheumatoid Arthritis: NF-κB-Inducing Kinase-Positive Endo 2015 Jul Tertiary lymphoid structures (TLSs) in chronic inflammation, including rheumatoid arthritis (RA) synovial tissue (ST), often contain high endothelial venules and follicular dendritic cells (FDCs). Endothelial cell (EC)-specific lymphotoxin β (LTβ) receptor signaling is critical for the formation of lymph nodes and high endothelial venules. FDCs arise from perivascular platelet-derived growth factor receptor β(+) precursor cells (preFDCs) that require specific group 3 innate lymphoid cells (ILC3s) and LTβ for their expansion. Previously, we showed that RA ST contains ECs that express NF-κB-inducing kinase (NIK), which is pivotal in LTβ-induced noncanonical NF-κB signaling. We studied the relation between NIK(+) ECs, (pre)FDCs, and ILC3s with respect to TLSs in RA ST. TLS(+) tissues exhibited a significantly increased expression of genes involved in noncanonical NF-κB signaling, including NIK, and immunohistochemical analysis revealed that NIK was almost exclusively expressed by ECs. ILC3s were present in human RA ST in very low numbers, but not differentially in TLS(+) tissues. In contrast, TLS(+) tissues contained significantly more NIK(+) ECs and perivascular platelet-derived growth factor receptor β(+) preFDCs, which correlated significantly with the quantity of FDCs. We established a strong link between NIK(+) ECs, (pre)FDCs, and the presence of TLSs, indicating that NIK(+) ECs may not only be important orchestrators of lymph node development but also contribute to the formation of TLSs in chronic inflammation.
25988705 Determining the Minimally Important Difference in the Clinical Disease Activity Index for 2015 Oct OBJECTIVE: Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimum clinically important differences (MCID) for some measures, such as the Clinical Disease Activity Index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity. METHODS: Data from Canadian Early Arthritis Cohort patients were used to examine absolute change in CDAI in the first year after enrollment, stratified by disease activity. MCID cut points were derived to optimize the sum of sensitivity and specificity versus the gold standard of patient self-reported improvement or worsening. Sensitivity, specificity, positive predictive values, and negative predictive values were calculated against patient self-reported improvement (gold standard) and for change in pain, Health Assessment Questionnaire (HAQ), and Disease Activity Score in 28 joints (DAS28) improvement. Discrimination was examined using the area under receiver operator curves. Similar methods were used to evaluate MCIDs for worsening for patients who achieved low disease activity. RESULTS: A total of 578 patients (mean ± SD age 54.1 ± 15.3 years, 75% women, median [interquartile range] disease duration 5.3 [3.3, 8.0] months) contributed 1,169 visit pairs to the improvement analysis. The MCID cut points for improvement were 12 (patients starting in high disease activity: CDAI >22), 6 (moderate: CDAI 10-22), and 1 (low disease activity: CDAI <10). Performance characteristics were acceptable using these cut points for pain, HAQ, and DAS28. The MCID for CDAI worsening among patients who achieved low disease activity was 2 units. CONCLUSION: These minimum important absolute differences in CDAI can be used to evaluate improvement and worsening and increase the utility of CDAI in clinical practice.
27671511 Effect of TNF-α Blockade in Gingival Crevicular Fluid on Periodontal Condition of Patient 2016 Sep BACKGROUND: Periodontitis and rheumatoid arthritis (RA) share a number of clinical and pathologic features, one of which is the presence of the tumor necrosis factor alpha (TNF-α)-induced bone resorption that is involved in the pathogenesis of both. OBJECTIVES: To investigate the effect of TNF-α blockade on periodontal conditions in patients with active RA. METHOD: The periodontal statuses of 36 patients (26 females, 10 males) diagnosed with active RA were evaluated both before and after anti-TNF-α therapy. Gingival index, bleeding on probing (BOP), probing pocket depth (PPD), oral hygiene index (OHI), and levels of TNF-α in gingival crevicular fluid (GCF) were measured at the baseline and 6 weeks after the treatment. Wilcoxon signed ranked test was used for statistical analyses. RESULTS: Based on OHI (p=0.860), the level of plaque control did not change during the study period, but there was a significant reduction in gingival inflammation based on the mean BOP (p=0.049) and GI (p=0.036) before and after 6 weeks of anti-TNF-α therapy. The mean PPD index did not significantly differ at the baseline and 6 weeks after treatment (p=0.126). CONCLUSION: Anti-TNF-α therapy might have a desirable effect on periodontal conditions and might reduce TNF-α level in GCF of patients with RA.
26178286 Breastfeeding and Risk of Rheumatoid Arthritis: A Systematic Review and Metaanalysis. 2015 Sep OBJECTIVE: Previous studies have examined the association between breastfeeding and rheumatoid arthritis (RA), but their results were inconsistent. The aim of this study was to perform a metaanalysis to clarify the effect of breastfeeding on RA risk. METHODS: The PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang databases were searched for relevant studies published up to September 10, 2014. Data were extracted, and multivariable-adjusted OR with 95% CI were pooled in the random-effects model. RESULTS: A total of 6 studies were included in the metaanalysis (RA cases: 1672, sample size: 143,670). Overall, an inverse association between breastfeeding and RA was observed (OR 0.675, 95% CI 0.493-0.924, p = 0.014). In the subgroup analysis, decreased RA risk was also found in both breastfeeding 1-12 months (OR 0.783, 95% CI 0.641-0.957, p = 0.015) and breastfeeding > 12 months (OR 0.579, 95% CI 0.462-0.726, p < 0.0005). Sensitivity analysis and cumulative analysis further strengthened the validity of the results. No publication bias was found in this metaanalysis. CONCLUSION: This metaanalysis suggests that breastfeeding is associated with a lower risk of RA, no matter if breastfeeding time is longer or shorter than 12 months.
25771854 Reduced folate carrier-1 80G > A gene polymorphism is not associated with methotrexate tre 2016 Apr Methotrexate (MTX) is the most commonly used disease-modifying drug to treat rheumatoid arthritis (RA). Although there are no reliable molecular markers to predict the treatment response and adverse effects to MTX therapy, the polymorphisms in genes coding for MTX metabolizing enzymes and transporters may play a crucial role. The reduced folate carrier-1 (RFC-1) is a bidirectional anion exchanger which transports MTX and folinic acid. It is reported to influence MTX treatment response and adverse effects in some ethnic populations but not in others. It is also associated with susceptibility to various diseases including systemic lupus erythematosus (SLE). The present study was aimed at investigating the role of RFC-1 80G > A gene polymorphism in association with disease susceptibility, MTX treatment response and the MTX-induced adverse events in the South Indian Tamil patients with rheumatoid arthritis. The RFC-1 80G > A gene polymorphism was investigated in 327 patients with RA and in 322 healthy controls by PCR-RFLP method. It was found that the heterozygous RFC-1 80 GA genotype was associated with protection against RA [p = 0.02, odds ratio (OR) 0.69, 95 % confidence interval (CI) 0.50-0.95]. However, it was not found to be associated with MTX treatment response. The RFC-1 G allele frequency was higher in patients with adverse effects, but the difference was not statistically significant (p = 0.08, OR 1.44, 95 % CI 0.97-2.13). RFC-1 80G > A gene polymorphism confers protection for RA. However, it is not associated with MTX treatment response and MTX-induced adverse effects in South Indian Tamil patients with RA.
26077402 Genetic Factors for the Severity of ACPA-negative Rheumatoid Arthritis in 2 Cohorts of Ear 2015 Aug OBJECTIVE: Rheumatoid arthritis (RA) that is negative for anticitrullinated protein antibodies (ACPA) is a subentity of RA, characterized by less severe disease. At the individual level, however, considerable differences in the severity of joint destruction occur. We performed a study on genetic factors underlying the differences in joint destruction in ACPA-negative patients. METHODS: A genome-wide association study was done with 262 ACPA-negative patients with early RA included in the Leiden Early Arthritis Clinic and related to radiographic joint destruction over 7 years. Significant single-nucleotide polymorphisms (SNP) were evaluated for association with progression of radiographic joint destruction in 253 ACPA-negative patients with early RA included in the Better Anti-Rheumatic Farmaco Therapy (BARFOT) study. According to the Bonferroni correction of the number of tested SNP, the threshold for significance was p < 2 × 10(-7) in phase 1 and 0.0045 in phase 2. In both cohorts, joint destruction was measured by Sharp/van der Heijde method with good reproducibility. RESULTS: Thirty-three SNP associated with severity of joint destruction (p < 2 × 10(-7)) in phase 1. In phase 2, rs2833522 (p = 0.0049) showed borderline significance. A combined analysis of both the Leiden and BARFOT datasets of rs2833522 confirmed this association with joint destruction (p = 3.57 × 10(-9)); the minor allele (A) associated with more severe damage (for instance, after 7 yrs followup, patients carrying AA had 1.22 times more joint damage compared to patients carrying AG and 1.50 times more joint damage than patients carrying GG). In silico analysis using the ENCODE and Ensembl databases showed presence of H3K4me3 histone mark, transcription factors, and long noncoding RNA in the region of rs2833522, an intergenic SNP located between HUNK and SCAF4. CONCLUSION: Rs2833522 might be associated with the severity of joint destruction in ACPA-negative RA.
26906298 Bone Mineral Density in Patients With Rheumatoid Arthritis and 4-Year Follow-up Results. 2016 Mar BACKGROUND: Osteoporosis is a common complication in patients with rheumatoid arthritis (RA). The change of bone mineral density (BMD) in patients with RA is slow, and little data are known about the long-term change of BMD. OBJECTIVES: This study aimed to determine the frequency of osteoporosis and the long-term change on BMD in a cohort of Chinese patients with RA routinely receiving calcium and vitamin D supplementation. METHODS: A total of 304 consecutive patients with RA were recruited. Bone mineral density measurements of the forearm, lumbar spine, and total hip were performed by dual-energy x-ray absorptiometry and compared with 200 age- and sex-matched healthy controls. Risk factors were analyzed by logistic regression models. RESULTS: The prevalence of osteoporosis at all measured sites in patients with RA was statistically significantly higher than in healthy controls. A total of 107 patients of the cohort had a mean of 4 years of follow-up. More patients with BMD decrease were found without calcium and vitamin D use compared with those who continuously took calcium and vitamin D (64.3% vs 19.8% at the forearm and 28.6% vs 16.1% at the total hip, respectively). Only the use of calcium and vitamin D supplementation was associated with a decreased risk of BMD decrease both at the forearm and at the total hip. CONCLUSIONS: Osteoporosis is common in Chinese patients with RA. Routine use of calcium and vitamin D supplementation decreased the risk of BMD decrease and should be recommended for all patients with RA.
25190551 Regulation of serum matrix metalloproteinases and tissue inhibitor of metalloproteinases-1 2015 Apr In our article, we evaluated the regulatory effects of the infusions of rituximab, a monoclonal antibody directed against CD20(+) B cells, on the serum matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in patients with active rheumatoid arthritis (RA) not responding to anti-tumor necrosis factor (anti-TNF) therapy. Twelve RA patients were planned to receive four infusions of 1,000 mg of rituximab at weeks 0, 2, 24 and 26. The therapy was combined with methotrexate (MTX) (20-30 mg/week). Seven patients were refractory to previously received infliximab, and five to etanercept. Serum concentrations of interstitial collagenase (MMP-1), stromelysin-1 (MMP-3), gelatinase B (MMP-9) and TIMP-1 were measured by ELISA on weeks 0, 2, 12, 24, 36 and 52. Initial infusion of rituximab downregulated serum MMP-1 (p < 0.01), MMP-3 (p < 0.001), MMP-9 (p < 0.001) and TIMP-1 (p < 0.05) levels. Second drug administration caused even more remarkable reduction of measured MMPs (p < 0.001 in all cases) and TIMP-1 level (p < 0.01). These findings were accompanied by significantly decreased ratios of measured MMPs to TIMP-1. Next rituximab infusions on weeks 24 and 26 sustained the suppression of serum MMPs levels. Prior to the initial rituximab infusion, serum concentrations of studied MMPs and TIMP-1 significantly correlated with markers of RA activity such as disease activity score (DAS28) and CRP levels. Rituximab therapy, beside a rapid clinical improvement, reduced serum MMPs concentrations in RA patients refractory to anti-TNF treatment. Repeated infusions of rituximab maintained initial serum MMPs suppression.
26715653 Protective effect of HLA-DRB1*13 alleles during specific phases in the development of ACPA 2016 Oct OBJECTIVE: Human leucocyte antigen (HLA)-DRB1*13 alleles are associated with protection from anticitrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA). It is, however, unknown at which phase of disease development (seroconversion, ACPA maturation, disease onset or outcome) these alleles are most important. We therefore examined the effect of HLA-DRB1*13 on: ACPA presence (systemic autoimmunity associated with RA) in individuals with and without RA, on ACPA characteristics and on clinical outcome measures. METHODS: The effect of HLA-DRB1*13 on ACPA presence in subjects with or without RA (non-RA) was assessed in the Swedish twin registry (n=10 748). ACPA characteristics were studied in patients with ACPA-positive RA from the Swedish Epidemiological Investigation of RA (EIRA, n=1224) and the Dutch Leiden Early Arthritis Clinic (EAC, n=441). Disease activity at inclusion and disease outcome (disease-modifying antirheumatic drugs (DMARD)-free sustained remission and radiographic progression) was assessed in patients with RA from the EAC. RESULTS: HLA-DRB1*13 is associated with protection from ACPA-positive RA (prevalence 16% vs 28% in ACPA-negative non-RA), but not with significant protection from ACPA in individuals without RA (prevalence: 22%, p value 0.09). HLA-DRB1*13 is associated with lower ACPA-levels (EIRA: 447 U/ml versus 691 U/ml, p value= 0.0002) and decreased citrullinated epitope recognition (EIRA: p<0.0001). No association between HLA-DRB1*13 and disease activity or outcome was found. CONCLUSIONS: These data indicate that HLA-DRB1*13 mainly affects the onset of ACPA-positive RA in ACPA-positive non-RA individuals. In RA, HLA-DRB1*13 influences ACPA characteristics but not the disease course. This implies that therapeutic strategies aimed at emulating the HLA-DBR1*13 protective effect may be most effective in ACPA-positive healthy individuals at risk for RA.
26398459 Periodontitis Response to Anti-TNF Therapy in Ankylosing Spondylitis. 2015 Oct BACKGROUND: Recently, it has been demonstrated that patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) have a higher risk of periodontitis; however, the effect of anti-TNF therapy in periodontal status of patients with AS and particularly in dental attachment is not known. OBJECTIVE: To evaluate longitudinally the local periodontal effect of TNF-antagonist in AS and compare to patients with RA. METHODS: Fifteen patients with AS and 15 RA control patients were prospectively evaluated at baseline and after 6 months (6 M) of anti-TNF therapy. Periodontal assessment included: probing pocket depth (PPD), clinical attachment level (CAL), gingival bleeding index, and plaque index. Rheumatologic clinical and laboratory evaluations were the following: Bath AS Disease Activity Index, Bath AS Metrology Index, Bath AS Functional Index, C-reactive protein and erythrocyte sedimentation rate for AS and Disease Activity Score 28 joints, and C-reactive protein and erythrocyte sedimentation rate for patients with RA. RESULTS: At baseline, periodontal parameters were alike in AS and RA (P > 0.05). After 6 M of anti-TNF therapy, clinical and laboratory parameters of rheumatic diseases decreased significantly in the patients with AS and RA (P < 0.05). A significant improvement in periodontal attachment measurements were observed in the patients with AS (PPD, 2.18 vs 1.94 mm; P = 0.02; CAL, 2.29 vs.2.02 mm; P = 0.03), but not in RA (PPD, 1.92 vs 2.06 mm; P = 0.06; CAL, 2.14 vs 2.28 mm; P = 0.27). Oral hygiene and gingival inflammation remained unchanged from baseline to 6-M evaluation in AS and RA (P > 0.05). CONCLUSION: Patients with AS under anti-TNF improved periodontal attachment. The mechanism for this effect needs further studies.
26682920 Post-September 11, 2001, Incidence of Systemic Autoimmune Diseases in World Trade Center-E 2016 Jan OBJECTIVE: To estimate the incidence of selected systemic autoimmune diseases (SAIDs) in approximately 14,000 male rescue/recovery workers enrolled in the Fire Department of the City of New York (FDNY) World Trade Center (WTC) Health Program and to compare FDNY incidence to rates from demographically similar men in the Rochester Epidemiology Project (REP), a population-based database in Olmsted County, Minnesota. PATIENTS AND METHODS: We calculated incidence for specific SAIDs (rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, and others) and combined SAIDs diagnosed from September 12, 2001, through September 11, 2014, and generated expected sex- and age-specific rates based on REP rates. Rates were stratified by level of WTC exposure (higher vs lower). Standardized incidence ratios (SIRs), which are the ratios of the observed number of cases in the FDNY group to the expected number of cases based on REP rates, and 95% CIs were calculated. RESULTS: We identified 97 SAID cases. Overall, FDNY rates were not significantly different from expected rates (SIR, 0.97; 95% CI, 0.77-1.21). However, the lower WTC exposure group had 9.9 fewer cases than expected, whereas the higher WTC exposure group had 7.7 excess cases. CONCLUSION: Most studies indicate that the healthy worker effect reduces the association between exposure and outcome by about 20%, which we observed in the lower WTC exposure group. Overall rates masked differences in incidence by level of WTC exposure, especially because the higher WTC exposure group was relatively small. Continued surveillance for early detection of SAIDs in high WTC exposure populations is required to identify and treat exposure-related adverse effects.
26315962 Radiologic damage at baseline predicts patient-related outcomes 18 years after the initiat 2015 Sep OBJECTIVES: We aimed to assess the association of the degree of radiologic damage at baseline with long-term patient-related outcomes (PRO) in patients with severe rheumatoid arthritis (RA). METHODS: This prospective observational single-centre study (Ratingen, Germany) included all RA patients starting treatment with methotrexate (MTX) between 1980 and 1987. Standardised clinical evaluations and radiographs of hands and feet were obtained at baseline and during the following years. About 18 years later, patients were invited for a re-assessment. PRO were assessed in three dimensions according to the International Classification of Functioning and Disability (ICF). Statistical analyses comprised multivariable models using baseline values for radiologic damage of hands and feet, age, gender, disease duration, rheumatoid factor positivity, measures of disease activity, and response to MTX as covariates. RESULTS: At baseline, the mean disease duration was 8.5 years. The disease was active with a mean number of swollen joints of 18 (out of 32) and a mean erythrocyte sedimentation rate of 55 mm/hour. Radiologic damage was present in 95% of the patients. After 18 years, patient-related outcomes could be assessed in 78/271 patients (29%). Among chosen covariates, only the degree of baseline radiologic damage as measured by the Ratingen score was predictive of all long-term PRO (p<0.016). CONCLUSIONS: In this cohort including patients with severe RA, baseline radiologic damage was a good long-term predictor of PRO related to all three ICF dimensions.
26455141 [CEMENTLESS TOTAL HIP ARTHROPLASTY AND IMPACTED BONE GRAFTING FOR PROTRUSIO ACETABULI IN P 2015 Feb OBJECTIVE: To evaluate the effectiveness of total hip arthroplasty (THA) with impacted autologous bone grafting and a cementless cup in the treatment of rheumatoid arthritis (RA) with protrusio acetabuli. METHODS: Between January 2001 and April 2009, 18 cases (20 hips) of RA with protrusio acetabuli were treated, including 6 males and 12 females with an average age of 46 years (range, 36-62 years). The disease duration was 3-10 years (mean, 6 years). Preoperative Harris score was 40.25 ± 6.68. The protrusio acetabuli was (5.70 ± 4.26) mm. According to Sotelo-Garza and Charnley classification criterion, there were 12 hips of type 1 (protrusio acetabuli 1-5 mm), 5 hips of type 2 (6-15 mm), and 3 hips of type 3 (>15 mm). All patients received THA with impacting bone graft and cementless prosthesis for recovery of acetabular center of rotation. RESULTS: The average operation time was 74 minutes (range, 48-126 minutes); the average blood loss was 350 mL (range, 150-650 mL). Deep venous thrombosis of lower extremity and poor healing of incision occurred in 3 and 2 cases respectively. Other patients achieved primary healing of incisions. The mean time of follow-up was 108 months (range, 60-156 months). According to X-ray films, bone grafting fusion was observed within 6 months after operation. At last follow-up, the Harris score was 87.20 ± 4.21, showing significant difference when compared with preoperative score (t = -27.68, P = 0.00); the protrusio acetabuli was (-1.11 ± 0.45) mm, showing significant difference when compared with preoperative value (t = 5.66, P = 0.00). No loosening of acetabular components was found. CONCLUSION: For RA patients with protrusio acetabuli, THA with impacted autologous bone grafting and a cementless cup has satisfactory medium-term effectiveness.
26048347 Meaning-focused coping, pain, and affect: a diary study of hospitalized women with rheumat 2015 Dec PURPOSE: The aim of the study was to investigate the relationship between affective state, pain, and coping in hospitalized women with rheumatoid arthritis, including both between- and within-person perspectives. METHODS: Participants were 95 female patients between 24 and 82 years of age (M = 50.91; SD = 13.80). For three consecutive days, they rated each night their state affect (positive and negative), pain level, and coping strategies (emotion-, problem- and meaning-focused ones). Relations among variables were tested with a multilevel approach with time included as a covariate. RESULTS: Within-person meaning-focused coping suppressed the negative pain effect on emotional state, but only for positive affect (Sobel's z = 2.07, p = .04). Moderators of the pain-affect relationship were between-person differences in pain level (B = -.23, SE = .08, t = -2.884, p = .004) and in meaning-focused coping (B = -.63, SE = .20, t = -2.097, p = .04). Specifically, suppression was significant only for patients who reported lower than sample average pain levels and for patients who reported lower than sample average use of meaning-focused strategies. CONCLUSIONS: Findings indicated that meaning-focused coping can be a crucial strategy for keeping daily positive affect in the face of chronic pain and how this effect is modified by interindividual differences. Even if restricted to the specific context, it may inform an intervention for hospitalized women with rheumatoid arthritis.
25510954 TNFα polymorphism as marker of immunosenescence for rheumatoid arthritis patients. 2015 Jan BACKGROUND: Expansion of CD4(+)CD28(null), a common feature of immunosenescence, which has been reported in rheumatoid arthritis (RA) patients, may also be associated with a CD4(+) imbalance. Although the increase of CD4(+)CD28(null) cells has been related to TNFα exposure, nothing is known about the possible role of genetic variants of this cytokine. METHODS: Participants were genotyped for TNFA rs1800629 (-308 G>A) and frequency of the CD4(+)CD28(null), regulatory T cells and Th1 cells subsets were quantified in peripheral blood samples by flow cytometry in 129 RA patients and 33 healthy controls. RESULTS: The expansion of CD4(+)CD28(null) cells in RA patients was associated with TNFA genotype, even at diagnosis, and linked to markers of aggressive disease in patient carriers of the minor allele. Analysis of regulatory T cells and IFNγ-CD4(+) expression suggested that defective suppression and/or Th1-shift could underlie the expansion of this population in these patients. Finally, although treatment with TNFα-blockers reduced CD4(+)CD28(null) cells in most patients, only those carriers of the common GG genotype reached values within the range of HC and showed a disease activity improvement correlated to this decrease. CONCLUSIONS: Our results provide evidence for a genetic basis of the premature immunosenescence of RA patients and highlight its potential role in clinical outcome after TNFα blockade.
26806309 Local fibroblast proliferation but not influx is responsible for synovial hyperplasia in a 2016 Feb 12 Synovial fibroblasts play crucial roles in inflammation and joint destruction in rheumatoid arthritis (RA). How they accumulate in the RA joints remains unclear. This study was conducted to discern whether cellular influx from the outside of the joints and local proliferation are responsible for synovial fibroblast accumulation in an animal model of RA. We found that synovial fibroblasts were identified as GFP+ cells using collagen type I alpha 2 (Col1a2)-GFP transgenic reporter mice. Then, bone marrow transplantation and parabiosis techniques were utilized to study the cellular influx. Irradiated wild-type mice were transplanted with bone marrow from Col1a2-GFP mice. Col1a2-GFP and wild-type mice were conjoined for parabiosis. The transplanted mice and the parabionts were subjected to collagen antibody-induced arthritis (CAIA). We found no GFP+ cells in the hyperplastic synovial tissues from the transplanted mice with CAIA and from the wild-type parabionts with CAIA. Furthermore, normal and CAIA synovial tissues from Col1a2-GFP mice and from fluorescent ubiquitination-based cell cycle indicator (Fucci) transgenic mice, in which cells in S/G2/M phases of the cell cycle express Azami-Green, were studied for Ki67, a cellular proliferation marker, and vimentin, a fibroblast marker, expression. The percentages of Ki67+/GFP+ and Azami-Green+/vimentin+ cells in the CAIA synovial tissues were higher than those in the untreated synovial tissues (34% vs. 0.40% and 19% vs. 0.26%, respectively). These findings indicate that local fibroblast proliferation but not cellular influx is responsible for the synovial hyperplasia in CAIA. Suppression of proliferation of the local synovial fibroblasts should be a promising treatment for RA.
25450406 Arthritogenic T cells in autoimmune arthritis. 2015 Jan Autoimmune diseases, including arthritis, often result from an imbalance between regulatory T (Treg) cells and IL-17-producing (Th17) cells. Dozens of studies in mice and humans have shed light on the pathological significance of T cells in RA. Since Th17 cells play an important role in the exacerbation of inflammation and bone destruction in joints, it has been an important issue how arthritic Th17 cells arise. Th17 cells are generated in the local inflammatory milieu via cytokines produced by macrophages or synovial fibroblasts, while it is reported that Th17 cells are generated in the gut in the presence of specific commensal bacteria. A recent report showed a pathogenic Th17 cell subset with a distinct pattern of gene expression and a potent osteoclastogenic ability are converted from Foxp3(+) T cells in arthritic joints. Since Foxp3(+) Treg cells contain T cells which recognize self-antigens, the fate of plastic Foxp3(+) T cells can be a critical determinant of autoimmunity or self-tolerance. Further analysis on the molecular basis and antigen-specificity of arthritogenic Th17 cell subsets will be helpful to establish novel therapeutic approaches and clarify how self-tolerance breaks down in autoimmune arthritis.