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ID PMID Title PublicationDate abstract
27525538 Predictive Risk Factors of Cervical Spine Instabilities in Rheumatoid Arthritis: A Prospec 2017 Apr 15 STUDY DESIGN: A prospective multicenter cohort study for more than 10 years of outpatients with rheumatoid arthritis (RA). OBJECTIVE: To identify predictive risk factors of cervical spine instabilities, which may induce compression myelopathy in patients with RA. SUMMARY OF BACKGROUND DATA: Many reports described the natural course of cervical spine involvement in RA. Only a few studies, however, conducted comprehensive evaluation of its prognostic factors. METHODS: Cervical spine instability was radiographically defined as atlantoaxial subluxation with the atlantodental interval greater than 3 mm, vertical subluxation (VS) with the Ranawat value less than 13 mm, and subaxial subluxation with irreducible translation of 2 mm or higher. The "severe" category of instability was defined as atlantoaxial subluxation with the atlantodental interval of 10 mm or lower, vertical subluxation with the Ranawat value of 10 mm or higher, and subaxial subluxation with translation of 4 mm or higher or at multiple levels. Of 503 "definite" or "classical" patients with RA without baseline "severe" instability, 143 were prospectively followed throughout for more than 10 years. The Cox proportional hazards regression analysis was performed to determine predictors for the development of "severe" instabilities. To exclude biases from the low follow-up rate, similar assessments were performed in 223 patients followed for more than 5 years from baseline. RESULTS: The incidence of cervical spine instabilities and "severe" instabilities significantly increased during more than 10 years in both 143 and 223 cohorts (all P < 0.01). Multivariable Cox proportional hazards models found that baseline mutilating changes (hazard ratio [HR]=19.15, 95% confidence interval [95% CI] = 3.96-92.58, P < 0.01), corticosteroid administration (HR = 4.00, 95% CI = 1.76-9.11, P < 0.01), and previous joint surgery (HR = 1.99, 95% CI = 1.01-3.93, P = 0.048) correlated with the progression to "severe" instability in 143 cases and also in 223 cases (HR = 8.12, 95% CI = 2.22-29.64, P < 0.01; HR = 3.31, 95% CI = 1.68-6.53, P < 0.01; and HR = 2.07, 95% CI = 1.16-3.69, P = 0.014, respectively). CONCLUSION: Established mutilating changes, concomitant corticosteroid treatment, and previous joint surgery are relatively robust indicators for a poor prognosis of the cervical spine in patients with RA, based on the consistency in more than 10-year analysis of two different settings. LEVEL OF EVIDENCE: 3.
27909722 Expression of soluble programmed death-1 protein in peripheral blood regulatory T cells an 2017 Jan The present study aimed to investigate the role of the soluble programmed death‑1 (sPD-1) protein, which is released by peripheral blood regulatory T cells (Treg) during the progression of rheumatoid arthritis (RA). From October 2012 to May 2014, 82 RA patients (RA group) and 90 healthy volunteers (healthy controls; HC) were recruited. Cluster of differentiation (CD)4, CD25 and forkhead/winged helix transcription factor p3 (Foxp3) and expression of cytotoxic T lymphocyte associated antigen 4 (CTLA-4) and Foxp3 were detected by flow cytometry. Expression of sPD‑1 in Treg was detected by western blot analysis. Immunosuppressive activity of CD4+CD25‑ Treg was measured via thiazolyl blue in an MTT assay. ELISA was used to detect interleukin‑10 (IL‑10), transforming growth factor beta (TGF-β), interleukin-4 (IL-4), interferon‑γ (IFN-γ) and nuclear factor of activated T cells (NF‑AT). It was observed that in peripheral blood, CD4+CD25-FOXP3+/CD4+ levels were reduced in the RA group (P<0.001), and sPD‑1 levels were markedly higher (P<0.001), compared with the HC group. Additionally, it was observed that relative sPD‑1 protein expression in the small interfering RNA (siRNA)-sPD-1 treated group was reduced compared with the untreated and scrambled siRNA groups (all P<0.0001). The mean fluorescence intensity of CTLA-4 and Foxp3 decreased markedly upon transfection with siRNA-sPD-1 (P<0.001). Compared with the normal CD4+CD25‑ T group, optical density (OD)540 values, IFN-γ/IL-4 concentration ratio and NF‑AT activity in siRNA untreated and scramble groups reduced significantly (all P<0.001). OD540 value, IFN-γ/IL-4 concentration ratio and NF‑AT activity in the siRNA‑sPD‑1 group were significantly upregulated (all P<0.001). Therefore, sPD-1 may suppress the level of CD4+CD25‑ Tregs in the peripheral blood of RA patients, and may be involved in a variety of immune processes mediated by CD4+CD25‑ Tregs.
29145862 L161982 alleviates collagen-induced arthritis in mice by increasing Treg cells and down-re 2017 Nov 16 BACKGROUND: To investigate the effects and potential mechanism of L161982 (a kind of EP4 antagonist) on the collagen-induced arthritis (CIA) mice model. METHODS: The CIA mice model were first established by immunizing with Chicken Type II Collagen on DBA/1 mice. The CIA groups were administered once a day for 2 weeks with either 5 mg/kg L161982 by intraperitoneal injections (IP), 200 U celecoxib by intragastrical injections, or 100 μl PBS (IP). At the end of the study, total arthritis score and histopathologic examination were assessed to determine CIA severity. The plasma and tissue expressions of IL-17 and monocyte chemoattractant protein-1 (MCP-1) were detected by enzyme-linked immunosorbent assay (ELISA) and Immunohistochemical staining (IHC) respectively; The number of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) determined as a proportion of total CD4(+) cells in the lymph nodes and spleen. We also tested the proliferation of isolated Tregs and the ratio of Th17 polarization of Naïve T cells under the treatment of L161982 by BrdU assay and flow cytometry respectively. RESULTS: CIA mice treated with L161982 showed reduced arthritis scores, joint swellings, cracked cartilage surface, and less hyperplasia in the connective tissue of the articular cavity. Plasma and tissue IL-17 and MCP-1 decreased, while the proportion of Treg cells is increased both in the spleen and lymph nodes of CIA mice. Otherwise, L161982 have no direct effect on Tregs proliferation; a decreased tendency of Th17 polarization in vitro were observed in L161982-treated naïve T cells. CONCLUSION: Although less effective than Celecoxib, L161982 also resulted in a reduction of ankle joint inflammation in CIA mice. L161982 reduces the RA severity in CIA mice through inhibition of IL-17 and MCP-1, increasing Treg cells, and reducing inflammation. The mechanism of the reduction of IL-17 in plasma or tissue after administration of L161982 might be potentially derived from the suppression of CD4(+) T cells differentiation into Th-17 cells.
27980014 Stiffness Is the Cardinal Symptom of Inflammatory Musculoskeletal Diseases, Yet Still Vari 2017 Dec OBJECTIVE: The objectives of the Outcome Measures in Rheumatology (OMERACT) Stiffness special interest group (SIG) are to characterize stiffness as an outcome in rheumatic disease and to identify and validate a stiffness patient-reported outcome (PRO) in rheumatology. METHODS: At OMERACT 2016, international groups presented and discussed results of several concurrent research projects on stiffness: a literature review of rheumatoid arthritis (RA) stiffness PRO measures, a qualitative investigation into the RA and polymyalgia rheumatica patient perspective of stiffness, data-driven stiffness conceptual model development, development and testing of an RA stiffness PRO measure, and a quantitative work testing stiffness items in patients with RA and psoriatic arthritis. RESULTS: The literature review identified 52 individual stiffness PRO measures assessing morning or early morning stiffness severity/intensity or duration. Items were heterogeneous, had little or inconsistent psychometric property evidence, and did not appear to have been developed according to the PRO development guidelines. A poor match between current stiffness PRO and the conceptual model identifying the RA patient experience of stiffness was identified, highlighting a major flaw in PRO selection according to the OMERACT filter 2.0. CONCLUSION: Discussions within the Stiffness SIG highlighted the importance of further research on stiffness and defined a research agenda.
28801345 Molecular basis for increased susceptibility of Indigenous North Americans to seropositive 2017 Nov OBJECTIVE: The pathogenetic mechanisms by which HLA-DRB1 alleles are associated with anticitrullinated peptide antibody (ACPA)-positive rheumatoid arthritis (RA) are incompletely understood. RA high-risk HLA-DRB1 alleles are known to share a common motif, the 'shared susceptibility epitope (SE)'. Here, the electropositive P4 pocket of HLA-DRB1 accommodates self-peptide residues containing citrulline but not arginine. HLA-DRB1 His/Phe13β stratifies with ACPA-positive RA, while His13βSer polymorphisms stratify with ACPA-negative RA and RA protection. Indigenous North American (INA) populations have high risk of early-onset ACPA-positive RA, whereby HLA-DRB1*04:04 and HLA-DRB1*14:02 are implicated as risk factors for RA in INA. However, HLA-DRB1*14:02 has a His13βSer polymorphism. Therefore, we aimed to verify this association and determine its molecular mechanism. METHODS: HLA genotype was compared in 344 INA patients with RA and 352 controls. Structures of HLA-DRB1*1402-class II loaded with vimentin-64Arg(59-71), vimentin-64Cit(59-71) and fibrinogen β-74Cit(69-81) were solved using X-ray crystallography. Vimentin-64Cit(59-71)-specific and vimentin(59-71)-specific CD4+ T cells were characterised by flow cytometry using peptide-histocompatibility leukocyte antigen (pHLA) tetramers. After sorting of antigen-specific T cells, TCRα and β-chains were analysed using multiplex, nested PCR and sequencing. RESULTS: ACPA(+) RA in INA was independently associated with HLA-DRB1*14:02. Consequent to the His13βSer polymorphism and altered P4 pocket of HLA-DRB1*14:02, both citrulline and arginine were accommodated in opposite orientations. Oligoclonal autoreactive CD4+ effector T cells reactive with both citrulline and arginine forms of vimentin(59-71) were observed in patients with HLA-DRB1*14:02(+) RA and at-risk ACPA(-) first-degree relatives. HLA-DRB1*14:02-vimentin(59-71)-specific and HLA-DRB1*14:02-vimentin-64Cit(59-71)-specific CD4+ memory T cells were phenotypically distinct populations. CONCLUSION: HLA-DRB1*14:02 broadens the capacity for citrullinated and native self-peptide presentation and T cell expansion, increasing risk of ACPA+ RA.
28932117 Multifunctional folate receptor-targeting and pH-responsive nanocarriers loaded with metho 2017 Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive cartilage and bone destruction. Activated macrophages that overexpress folic acid (FA) receptors play an important role in RA, due to their abundance in inflamed synovial membrane and joints. In an effort to deliver drugs to the inflamed tissues, multifunctional FA receptor-targeting and pH-responsive nanocarriers were developed. They were composed of lipids, polyethylene glycol (PEG)-poly(lactic-co-glycolic acid) (PLGA) forming a hydrophilic shell, FA around the hydrophilic shell as a targeting ligand, and poly(cyclohexane-1,4-diylacetone dimethylene ketal) (PCADK) and PLGA as a hydrophobic core. PCADK also acts as a pH-responsive material. Methotrexate (Mtx) was encapsulated in the nanoparticles, which exhibited pH-responsive release in vitro. Cellular uptake and cytotoxicity experiments revealed that FA-PEG-PLGA/PCADK-lipid nanoparticles loaded with Mtx (FA-PPLNPs) exhibited superior cellular uptake and higher cytotoxicity to activated macrophages than PPLNPs/Mtx. The therapeutic effect of FA-PPLNPs/Mtx in RA was confirmed in an adjuvant-induced arthritis rat model. These results suggest that the multifunctional folate receptor-targeting and pH-responsive nanocarriers are promising for the treatment of RA.
28940172 GP2015: An Etanercept Biosimilar. 2017 Dec GP2015 is the second biosimilar of the reference p75 TNF receptor-Fc fusion protein etanercept. It is approved for use in all indications for which reference etanercept is approved, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, non-radiographic axial spondyloarthritis, plaque psoriasis and paediatric plaque psoriasis. GP2015 has similar physiochemical and pharmacodynamic properties to those of reference etanercept, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers. GP2015 demonstrated clinical efficacy equivalent to that of reference etanercept in patients with moderate-to-severe plaque psoriasis; the tolerability, safety and immunogenicity profiles of the two agents were also generally similar. Switching between GP2015 and reference etanercept had no impact on clinical efficacy, tolerability or immunogenicity. The role of reference etanercept in the management of inflammatory autoimmune conditions is well established and GP2015 provides an effective biosimilar alternative for patients requiring etanercept therapy.
29441860 Suppression of infliximab antibody levels by azathioprine in patients with rheumatoid arth 2017 Feb 1 In rheumatoid arthritis (RA) treatment, the concomitant use of methotrexate has been shown to reduce the incidence of antibodies to infliximab (ATI), on the other hand, it is unclear whether azathioprine can reduce ATI production. We enrolled a total of 10 Japanese adult patients with RA who were treated with infliximab concomitantly with methotrexate or azathioprine. Serum concentrations of infliximab and ATI of these patients were measured. The mean serum infliximab concentrations was 1.6±1.3 μg/ml in patients with methotrexate and 1.0±0.5 μg/ml in patients with azathioprine. Serum ATI concentrations were below the limit of quantitation in 4 of 5 patients in each group. The results from the present study suggest that azathioprine suppresses ATI production.
28067815 Marine Oil Supplements for Arthritis Pain: A Systematic Review and Meta-Analysis of Random 2017 Jan 6 Arthritis patients often take fish oil supplements to alleviate symptoms, but limited evidence exists regarding their efficacy. The objective was to evaluate whether marine oil supplements reduce pain and/or improve other clinical outcomes in patients with arthritis. Six databases were searched systematically (24 February 2015). We included randomized trials of oral supplements of all marine oils compared with a control in arthritis patients. The internal validity was assessed using the Cochrane Risk of Bias tool and heterogeneity was explored using restricted maximum of likelihood (REML)-based meta-regression analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to rate the overall quality of the evidence. Forty-two trials were included; 30 trials reported complete data on pain. The standardized mean difference (SMD) suggested a favorable effect (-0.24; 95% confidence interval, CI, -0.42 to -0.07; heterogeneity, I² = 63%. A significant effect was found in patients with rheumatoid arthritis (22 trials; -0.21; 95% CI, -0.42 to -0.004) and other or mixed diagnoses (3 trials; -0.63; 95% CI, -1.20 to -0.06), but not in osteoarthritis patients (5 trials; -0.17; 95% CI, -0.57-0.24). The evidence for using marine oil to alleviate pain in arthritis patients was overall of low quality, but of moderate quality in rheumatoid arthritis patients.
26057130 B cells influence sex specificity of arthritis via myeloid suppressors and chemokines in h 2017 May Rheumatoid arthritis (RA) occurs two times more often in women than men. B cell depletion has been shown to be efficacious in treating RA. Our previous studies suggested that antigen presentation via B cells results in a sex-specific immune response in DR4 and DR4/DQ8 mice. Here we evaluated the mechanism of efficacy of the B cell depletion in treating arthritis-susceptible DQ8 mice. The data show that arthritic DQ8 mice treated with anti-CD20 antibody in therapeutic protocols show milder disease severity in females as compared to males, which is associated with decreased antibodies to citrullinated proteins and reduced levels of IL-23 and CCL5. Treatment led to significantly increased numbers of T regulatory and monocyte-derived suppressor F4/80+Gr1(hi) cells in females as compared to male DQ8 mice. Our observations suggest that therapeutic strategies that target B cells may benefit females while functions of DCs might be relatively more important for men than women.
28877868 Impact of risk factors associated with cardiovascular outcomes in patients with rheumatoid 2018 Jan OBJECTIVES: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA. METHODS: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions. RESULTS: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics). CONCLUSIONS: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA.
28412712 Antitumor Necrosis Factor-α Therapy Associated with Inflammatory Bowel Disease: Three Cas 2017 Jul OBJECTIVE: Antitumor necrosis factor-α (anti-TNF-α) therapy is the most prescribed biologic agent therapy in rheumatology and gastroenterology. However, a number of serious side effects have been reported with these drugs. Only a handful of cases of new-onset inflammatory bowel disease (IBD), mostly in children diagnosed with juvenile idiopathic arthritis (JIA), have been reported during anti-TNF-α therapy. We present 3 cases of adult IBD following anti-TNF-α therapy and a literature review on this topic. METHODS: We searched PubMed MESH for all relevant terms, papers were reviewed, and patient-specific data were extracted. Relevant clinical data were calculated and presented. RESULTS: The PubMed search resulted in 137 articles, of which 11 articles and 4 cited publications were included in our analysis. We found 53 cases of IBD after anti-TNF-α therapy reported in the literature; most of them were case series collected retrospectively from national databases or studies. Almost all the patients developed IBD after the introduction of etanercept (ETN); 2 patients with rheumatoid arthritis were also included. The average age at IBD onset was 17.3 years and the average time from ETN introduction to IBD onset was 27 months (± 24). Gastrointestinal symptoms have been reported as improving or subsiding in most of the patients after discontinuing ETN. CONCLUSION: Although this manifestation is not common, it should be taken into consideration as an adverse effect of ETN. Rheumatologists, and in particular rheumatologists treating adult patients, should be aware of this possible complication. Further investigation about the pathogenic process underlying this phenomenon is warranted.
29263468 [Performance of the 2015 ACR/EULAR classification criteria compared with other classificat 2017 Dec 18 OBJECTIVE: To evaluate the ability of 2015 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) classification criteria to diagnose gout compared with the widely used 1977 American Rheumatism Association (ARA) criteria and other criteria in clinical practice in Chinese patients, and to compare the sensitivity and specificity of different classification criteria for gout in early and established diseases. METHODS: The patients who had ankle arthritis and visited the Department of Rheumatology and Clinical Immunology, Peking University First Hospital between February 2012 and February 2016 were screened. The patients who had been already diagnosed with gout or pyrophosphate deposition disease through arthrocentesis or tissue aspiration and those who had been diagnosed with rheumatoid arthritis, spondyloarthritis, and osteoarthritis were excluded. The patients were diagnosed by two experienced rheumatologists and all of them were followed up for at least one year. Early disease was defined as symptom onset of no more than 2 years; established disease was defined as symptom duration of more than 2 years. The 2015 ACR classification criteria were divided into clinical form with clinical parameters included and complete form with not only clinical parameters but also synovial fluids tests, imaging findings and monosodium urate (MSU) included. The two forms above were short for "clinical form (incorporating clinical parameters)" and "complete form (incorporating imaging and MSU data)" respectively. RESULTS: In this study, 284 patients suffering from ankle arthritis were inclu-ded in the study, 219 of them were classified as gout and 65 of them had alternative diagnoses. The sensitivity and specificity of 2015 ACR complete form (incorporating imaging and MSU data) for diagnosing gout were 88.13% and 95.38%, respectively. The area under the curves (AUC) of 2015 ACR "complete form (incorporating imaging and MSU data)", 2015 ACR "clinical form (incorporating clinical parameters)", 2010 Netherlands criteria and 1977 ARA criteria were 0.982, 0.983, 0.963, and 0.928, respectively. For the 94 early gout patients, the AUC of the above criteria were 0.973, 0.968, 0.916, and 0.910, respectively. For the established gout patients, the AUC were 0.987, 0.991, 0.982, and 0.936, respectively. For the patients with disease duration within two years, the odd ratio (OR) for sensitivity of 2015 ACR "complete form (incorporating imaging and MSU data)", 2015 ACR "clinical form (incorporating clinical parameters)", 2010 Netherlands criteria and 1977 ARA criteria were 1.562 (1.003-2.435), 1.500 (1.001-2.346), and 1.812 (1.177-2.791), nevertheless, for the patients with established gout, the OR were 1.702 (1.300-2.229), 1.607 (1.224-2.110), and 1.821 (1.396-2.377), respectively. CONCLUSION: The 2015 ACR/EULAR criteria are more accurate in gout diagnosis compared with the 1977 ARA criteria by elevating the sensitivity and specificity, in respective of the disease duration. The 2015 ACR/EULAR criteria may serve as new diagnostic tools in daily clinical practice in Chinese patients.
28346333 Clinical Benefits of n-3 PUFA and ɤ-Linolenic Acid in Patients with Rheumatoid Arthritis. 2017 Mar 25 (1) Background: Marine n-3 polyunsaturated fatty acids (PUFA) and ɤ-linolenic acid (GLA) are well-known anti-inflammatory agents that may help in the treatment of inflammatory disorders. Their effects were examined in patients with rheumatoid arthritis; (2) Methods: Sixty patients with active rheumatoid arthritis were involved in a prospective, randomized trial of a 12 week supplementation with fish oil (group I), fish oil with primrose evening oil (group II), or with no supplementation (group III). Clinical and laboratory evaluations were done at the beginning and at the end of the study; (3) Results: The Disease Activity Score 28 (DAS 28 score), number of tender joints and visual analogue scale (VAS) score decreased notably after supplementation in groups I and II (p < 0.001). In plasma phospholipids the n-6/n-3 fatty acids ratio declined from 15.47 ± 5.51 to 10.62 ± 5.07 (p = 0.005), and from 18.15 ± 5.04 to 13.50 ± 4.81 (p = 0.005) in groups I and II respectively. The combination of n-3 PUFA and GLA (group II) increased ɤ-linolenic acid (0.00 ± 0.00 to 0.13 ± 0.11, p < 0.001), which was undetectable in all groups before the treatments; (4) Conclusion: Daily supplementation with n-3 fatty acids alone or in combination with GLA exerted significant clinical benefits and certain changes in disease activity.
29209104 T-Cell Subsets in Rheumatoid Arthritis Patients on Long-Term Anti-TNF or IL-6 Receptor Blo 2017 Data on the impact of biological therapies on the T-cell phenotype in rheumatoid arthritis are limited. Here, we prospectively measured the percentages of 15 circulating T-cell subtypes using flow cytometry. We obtained transversal and longitudinal data in 30 anti-TNF responders, 19 secondary anti-TNF nonresponders, and 43 IL-6R antagonist responders, before, 8 weeks and at least 6 months after biological therapy. Untreated RA patients and healthy controls were also included. The important findings are the following: (1) the proportion of regulatory T-cells (Tregs) which are decreased in untreated RA patients becomes normal in all long-term-treated groups; (2) in anti-TNF responders as well as in nonresponders, the frequencies of naïve CD4+ and CD8+ cells are lower, whereas those of proinflammatory Th1, Th2, and Th17 cells and HLA-DR+-activated cells are higher than those in untreated RA or healthy controls; (3) in IL-6R responders, Th1 proportion is decreased, while that of Th2 and Th17 is increased as compared to that in anti-TNF-treated patients and controls; (4) pending confirmation, a CD4CD69 ratio < 2.43 at baseline, could be useful to predict a good therapeutic response to anti-TNF therapy. This study provides comprehensive information regarding the long-term impacts of those biological therapies on the ecotaxis of T-cells in RA. The ClinicalTrials.gov registration number of our study is NCT03266822.
28073043 Periplocoside A ameliorated type II collagen-induced arthritis in mice via regulation of t 2017 Mar Periplocoside A (PSA) has been extracted from the Chinese herbal medicine Periploca sepium Bge to treat rheumatoid arthritis (RA) via immune regulation. We previously found that PSA exhibits immunosuppressive activity both in vitro and in vivo. Balanced regulation of helper T 17 (Th17)/regulatory T (Treg) cells is the current therapeutic direction for the treatment of RA. The present study investigated the mechanism of PSA in treating collagen-induced arthritis (CIA). The therapeutic effects and potential pharmacological mechanisms of PSA were specifically clarified by examining its effects on CIA in DBA/1 mice. PSA administration significantly relieved the severity of the arthritis, and preventive administration of PSA reduced the incidence of arthritis in the mice with CIA and relieved joint damage in terms of morphology. PSA was also able to reduce the levels of anti-collagen II (CII) antibodies and pro-inflammatory cytokines in the serum. As a result, the proportion of Th17 cells decreased, and the proportion of Treg cells increased. A follow-up study of the ex vivo immunological reactions induced by a specific antigen found that PSA suppressed lymphocyte proliferation, inhibited the differentiation and reactivity of Th17 cells, and promoted the proportion of Treg cells among helper T cells. PSA also exhibited pharmacological effect in regulating the balance between Th17 and Treg cells in CIA through relevant signalling pathways. Thus, PSA played a specific role in CIA treatment. In particular, our results suggest that the therapeutic effects of PSA on RA are partially realized via the regulation of the balance of Th17/Treg cells.
29216228 Primary prevention of myocardial infarction with angiotensin-converting enzyme inhibitors 2017 BACKGROUND: Rheumatoid arthritis (RA) is regarded as a high risk factor for myocardial infarction. Hypertension is a major modifiable risk factor contributing to increased risk of myocardial infarction (MI). Dual blood pressure (BP)-lowering and anti-inflammatory effect of renin-angiotensin-system (RAS) inhibitors may possess protective effect from MI in RA population. However, treatment of hypertension with RAS inhibitors and MI in RA population remains unclear. METHODS: We investigated whether RAS blockade could decrease risk of incident MI in hypertensive patients with RA. We identified patients with RA and hypertension from the Registry for Catastrophic Illness, a nation-wide database encompassing almost all of the RA patients in Taiwan from 1995 to 2008. The primary endpoint was MI and the median duration of follow up was 2,986 days. Propensity score weighting and Cox proportional hazards regression models were used to estimate hazard ratios for MI. RESULTS: Among 27,335 subjects, 9.9% received angiotensin-converting enzyme inhibitors (ACEIs), 25.9% received angiotensin II receptor blockers (ARBs) and 20.0% received ACEIs or ARBs alternatively. The incidence of MI significantly decreased in patients treated with ACEIs (hazard ratio 0.707; 95% confidence interval 0.595-0.840), ARBs (0.641; 0.550-0.747) and ACEIs/ARBs (0.631; 0.539-0.739). The protective effect of ACEI or ARB therapy was significantly better in patients taking longer duration. The effect remained robust in subgroup analyses. CONCLUSIONS: Therapy of ACEIs or ARBs is associated with a lower risk of MI among patients with RA. Hence, hypertension in patients with RA could comprise a compelling indication for RAS inhibitors.
28913776 Interactions of antisera to different Chlamydia and Chlamydophila species with the ribosom 2017 Dec Chlamydia trachomatis (CT) and the Chlamydophila species (CS) Chlamydophila pneumoniae (CPn), and Chlamydophila psittaci (CPs) are suggested to induce autoantibodies causative of several human autoimmune disorders like rheumatoid arthritis and systemic lupus erythematosus (SLE). The aim of the present study was therefore to identify cellular protein interaction partners with antisera to CT (α-CT) or CS (α-CS) and to identify functional consequences of such interaction in vitro. As detected with a commercial first trimester human prenatal brain multiprotein array (hEXselect, Engine, Germany), the most frequent interaction partner with both α-CT and α-CS was the ribosomal small subunit protein RPS27a. This could be confirmed by Western blot analysis with a recombinant RPS27a sample. In addition, immunocytochemistry with both antisera in the human choroid plexus papilloma cell line HIBCPP revealed a granular cytoplasmic staining, and Western blot analysis with whole-cell protein samples of HIBCPP cells revealed both antisera to label protein bands of different molecular weights and intensity. By 2D Western blot analysis and mass spectrometry, one of the protein spots interacting with α-CT could be identified as the RPS27a. Finally, two different methods for the detection of protein synthesis activity, the SUnSET technique and an HPG fluorescence assay revealed both antisera to cause reduced translational activity in HIBCPP cells. Together with previous findings of RPS27a as an autoimmune target in a mouse model of systemic lupus erythematosus (SLE), these results suggest that infections with CT and/or CS could induce SLE-associated immune modifications. However, direct evidence for a pathogenic role of these interactions for SLE demands further investigations.
28127155 The Histone Modification Code in the Pathogenesis of Autoimmune Diseases. 2017 Autoimmune diseases are chronic inflammatory disorders caused by a loss of self-tolerance, which is characterized by the appearance of autoantibodies and/or autoreactive lymphocytes and the impaired suppressive function of regulatory T cells. The pathogenesis of autoimmune diseases is extremely complex and remains largely unknown. Recent advances indicate that environmental factors trigger autoimmune diseases in genetically predisposed individuals. In addition, accumulating results have indicated a potential role of epigenetic mechanisms, such as histone modifications, in the development of autoimmune diseases. Histone modifications regulate the chromatin states and gene transcription without any change in the DNA sequence, possibly resulting in phenotype alteration in several different cell types. In this paper, we discuss the significant roles of histone modifications involved in the pathogenesis of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary biliary cirrhosis, and type 1 diabetes.
28841334 Eyelid Merkel cell carcinoma in a patient treated with golimumab. 2018 Feb PURPOSE: To describe a clinical case of biopsy-proven Merkel cell carcinoma of the eyelid following golimumab therapy for rheumatoid arthritis (RA). METHODS: Interventional case report. RESULTS: A 73-year-old woman with a history of chronic RA presented with a right upper eyelid mass. She had been treated with golimumab (tumor necrosis factor (TNF) inhibitors) injection therapy for the past 6 months. A biopsy showed findings suggestive of a Merkel cell carcinoma of the eyelid. CONCLUSIONS: Merkel cell carcinoma may be associated with anti-TNF treatment and should be included in the differential diagnosis of an eyelid tumor in patients treated with TNF inhibitors.