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ID PMID Title PublicationDate abstract
27667464 [Xinfeng Capsule reduces hypercoagulative state in patients with Sjogren's syndrome by inh 2016 Oct Objective To explore the relationship between Xinfeng Capsule (XFC) improving the hypercoagulative state in patients with Sjogren's syndrome (SS) and miR-155/suppressor of cytokine signaling 1 (SOCS1)/nuclear factor κB (NF-κB) signaling pathway. Methods Sixty-six SS patients were randomly divided into XFC-treated group and hydroxychloroquine (HCQ)-treated control group (n=33 per group), which were respectively treated with XFC and HCQ. In addition, 20 healthy volunteers were enrolled as a normal control group. The levels of prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIG), thrombin time (TT) and D-dimer (D-D) were detected using automatic coagulation analyzer. Interleukin-1β (IL-1β), IL-4, IL-10, tumor necrosis factor-α (TNF-α), P50, P65, inhibitor of NF-κB α (IκBα) were tested using ELISA. Meanwhile, the mRNA expressions of p50, p65 and IκBα were determined using quantitative real-time PCR, and the level of microRNA-155 (miR-155) was examined by one-step fluorescence quantitative PCR. The protein levels of P50, P65 and SOCS1 were detected using Western blotting. Erythrocyte sedimentation rate (ESR) was evaluated by Westergren method. Hypersensitive C-reactive protein (hs-CRP) was detected using automatic biochemical analyzer. Results Compared with the normal control group, the levels of D-D and FIB significantly increased in SS group; simultaneously, the serum levels of miR-155, IL-1β, TNF-α, P50, P65, IκBα, hs-CRP, ESR were significantly elevated in SS patients, while IL-4 and IL-10 were significantly reduced. Spearman correlation analysis showed that the coagulation parameters were remarkably correlated with cytokines, NF-κB and activity indexes. In the two treated groups, coagulation parameters and related indexes were demonstrated having some improvement, especially in the XFC group, which had a much higher efficiency, and better outcomes in reducing the levels of FIB, D-D, miR-155, TNF-α, IL-1β, P50, P65, ESR and hs-CRP, as well as increasing the expressions of SOCS1, IL-4 and IL-10. Conclusion XFC can significantly alleviate the hypercoagulative state of patients with SS, and the mechanisms may be related to the inhibition of miR-155/SOCS1/NF-κB signaling pathway.
25303223 Relationship between disease characteristics and orofacial manifestations in systemic scle 2015 May OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is associated with decreased saliva production and interincisal distance, more missing teeth, and periodontal disease. We undertook this study to determine the clinical correlates of SSc with these oral abnormalities. METHODS: Subjects were recruited from the Canadian Scleroderma Research Group cohort. Detailed dental and clinical examinations were performed according to standardized protocols. Associations between dental abnormalities and selected clinical and serologic manifestations of SSc were examined. RESULTS: One hundred sixty-three SSc subjects were included: 90% women, mean ± SD age 56 ± 11 years, mean ± SD disease duration 14 ± 8 years, 72% with limited cutaneous disease, and 28% with diffuse cutaneous disease. Decreased saliva production was associated with Sjögren's syndrome-related autoantibodies (β = -43.32; 95% confidence interval [95% CI] -80.89, -5.75), but not with disease severity (β = -2.51; 95% CI -8.75, 3.73). Decreased interincisal distance was related to disease severity (β = -1.02; 95% CI -1.63, -0.42) and the modified Rodnan skin thickness score (β = -0.38; 95% CI -0.53, -0.23). The number of missing teeth was associated with decreased saliva production (relative risk [RR] 0.97; 95% CI 0.94, 0.99), worse hand function (RR 1.52; 95% CI 1.13, 2.02), and the presence of gastroesophageal reflux disease (GERD; RR 1.68 [95% CI 1.14, 2.46]). No clinical or serologic variables were correlated with periodontal disease. CONCLUSION: In SSc, diminished interincisal distance is related to overall disease severity. Decreased saliva production is related to concomitant Sjögren's syndrome antibodies. Tooth loss is associated with poor upper extremity function, GERD, and decreased saliva. The etiology of excess periodontal disease is likely multifactorial and remains unclear.
25400173 Curcumin loaded solid lipid nanoparticles ameliorate adjuvant-induced arthritis in rats. 2015 Aug BACKGROUND: Rheumatoid arthritis (RA), a chronic and systemic inflammation, results in destruction of joints and cartilages. Effectiveness of curcumin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable curcumin loaded solid lipid nanoparticles (C-SLNs) for the treatment of RA. METHODS: In the present study, the protective effect of curcumin and its SLNs was evaluated in complete Freund's adjuvant (CFA)-induced arthritis in rats. RESULTS: Arthritic rats exhibited marked decrease in paw withdrawal threshold in Randall-Selitto and von Frey hair test along with decreased reaction time in hot plate. Arthritic rats also showed significant joint hyperalgesia, joint stiffness and increased paw volume along with marked decrease in mobility score. Arthritic rats showed a significant increase in blood leukocyte count, oxidative-nitrosative stress, tumour necrosis factor-α, C-reactive protein, cyclic citrullinated peptide antibody levels and radiological alterations in tibiotarsal joint. C-SLN administration (10 and 30 mg/kg), when compared with free curcumin (10 and 30 mg/kg), significantly and dose dependently ameliorated various symptoms of arthritis in rats, improved biochemical markers and preserved radiological alterations in joints of arthritic rats. CONCLUSIONS: The current findings suggest the protective potential of curcumin-SLNs in ameliorating CFA-induced arthritis in rats through attenuation of oxido-inflammatory and immunomodulatory cascade. Further, the results emphasize that SLNs are a novel approach to deliver curcumin into the inflamed joints and improve its biopharmaceutical performance.
27738392 High-Methionine Diet Attenuates Severity of Arthritis and Modulates IGF-I Related Gene Exp 2016 Rheumatoid arthritis, a synthesized form of adjuvant arthritis exhibited throughout many animal species, inhibits liver function and circulation of IGF-I and contributes to the degradation of skeletal muscle mass. One of the primary goals of the present study is determining whether a high-Methionine (high-Met) diet is capable of reducing the adverse effects of arthritis, namely, loss of body mass. Following adjuvant injection, forty arthritic rats were randomly assigned to either a control group with a basal diet or a high-Met group with the same basal diet + 0.5% Methionine. After 14 days all rats were terminated. The high-Met group exhibited an increase in body weight and food intake in comparison with the control group (P < 0.05). High-Met diet debilitated arthritis-induced surges in the gastrocnemius in both atrogin-1 and the MuRF1 expressions; however, it was observed to have little to no effect on atrogin-1 and MuRF1 gene expression in soleus. At the same time, high-Met diet rats experienced a rise in IGF-I, with lowering of IGFBP-3 gene expression in the gastrocnemius and the soleus. These data suggest that arthritis severity can be partly attenuated by high-Met diet.
26387164 [FULLERENE C60 INHIBITED FREE RADICAL AND DESTRUCTIVE PROCESSES IN CONNECTIVE TISSUE DURIN 2015 The effects of fullerene C60 (FC60) on the level of free radical and destruction processes were studied in rats with experimental adjuvant arthritis (AA). It was shown the protective effect of FC60 during AA. The effect was accompanied by an increase of the antioxidant enzymes activity, superoxide dismutase in the liver (15.96 ± 0.38 μmol/kg x s) and in the kidneys (5.36 ± 0.27 μmol/kg x s) and catalase in the kidneys (9.56 ± 0.78 μmol/kg x s) and in the heart (2.26 ± 0.41 μmol/kg x s) in comparison to control group (43.83± 5.69%; 54.55 ± 6.18%; 11.68 ± 0.52 μmol/kg x s; 3.43 ± 0.47 μmol/kg x s; 4.77 ± 0.5 μmol/kg x s; 0.98 ± 0.12 μmol/kg x s accordingly). It was shown a protective effect of FC60 during AA directed on the depression of the destructive processes in connective tissue that was expressed through the reduction of the total collagenolitic activity level in cartilage (10.05 ± 0.06 μmol/g/min) and bone (11.21 ± 0.04 μmol/g/min) tissues, free hydroxyproline contents (1.54 ± 0.04 μg/ml) and alkaline phasphatase activity (1.24 ± 0,14 μmol/l x sec) in comparison to control group (11.91 ± 0.49 μmol/g/min; 13.19 ± 0.15 μmol/g/min; 2.25 ± 0.07 μg/ ml; 2.19 ± 0.24 μmol/l x sec accordingly). Taken together, these results accentuate the perspective of future investigations of action FC60 during rheumatoid arthritis as a feasible therapeutic agent.
26946646 MABS: targeted therapy tailored to the patient's need. 2015 Sep Monoclonal antibodies (MABs) represent the window of opportunity in modern medicine. As immunology plays a vital role both in our survival and in disease development, MABs were found to be of great help in diagnosing, prognosticating and managing certain malignancies, inflammatory conditions, autoimmune as well as infectious diseases. Technological advances have enabled the production of MABs that target specific antigens linked with several disease processes. These drugs are now a component of therapy, not only for many common malignancies, including breast, colorectal, lung and pancreatic cancers, as well as lymphoma, leukaemia and multiple myeloma, but also for several inflammatory conditions such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis and inflammatory bowel disease. Targeted therapy has raised new questions about tailoring treatment, including cancer management, to the individual patient's needs. This would have a positive impact on the drug's effectiveness and toxicity as well as the economics of care. While targeted MABs are generally better tolerated than traditional chemotherapy, they are associated with several adverse effects, which vary from one patient to another.
27313424 In vivo antiarthritic activity of Rosa centifolia L. flower extract. 2015 Jul INTRODUCTION: Rosa centifolia L. (Rosaceae) have been used for the treatment of joint pain and rheumatoid arthritis (RA) in the traditional system of medicine. AIM: In this study, the antiarthritic activity of the alcoholic extract from the floral parts of R. centifolia was investigated. MATERIALS AND METHODS: The anti-inflammatory and antiarthritic activity of R. centifolia alcoholic extract (RCAE: 32, 64, and 128 mg/kg) was evaluated using the carrageenan-induced paw edema and complete Freund's adjuvant (CFA) induced arthritis model. Serum from arthritic rats was collected for the estimation of pro-inflammatory cytokine levels. Further, the safety of RCAE was evaluated in an acute and sub-acute (28-day) oral toxicity study. RESULTS: RCAE (64 and 128 mg/kg) significantly (P < 0.01) inhibited carrageenan-induced paw edema at 1, 3, and 6 h post carrageenan challenge and demonstrated significant (P < 0.01) antiarthritic activity on days 3, 7, 14, and 21 day following CFA immunization. Further, RCAE (128 mg/kg) treatment also produced a significant (P < 0.01) decrease in circulating pro-inflammatory cytokine levels as compared with control. Further, no toxicologically significant treatment-related effects were observed in the oral sub-acute toxicity study conducted with the extract. CONCLUSION: The result of study demonstrates the antiarthritic activity of R. centifolia and validates its traditional use for the treatment of RA.
27783110 [Arthrodesis of the proximal interphalangeal joint of fingers with tension band wire]. 2017 Oct OBJECTIVE: Arthrodesis of the proximal interphalangeal joint of fingers in a functional and pain-free position. INDICATIONS: Primary and secondary osteoarthritis, traumatic joint destruction, posttraumatic malposition, instability, joint destruction due to infection, irreparable extensor and/or flexor tendon lesion, recurrent flexion deformity in Dupuytren's disease, arthritis (e. g., rheumatoid arthritis, psoriatic arthritis), failed resection arthroplasty, failed prosthesis, congenital disorder (e. g., camptodactyly). CONTRAINDICATIONS: Persistent joint infection. SURGICAL TECHNIQUE: Resection of the proximal phalanx head and the middle phalanx base, arthrodesis with figure-of-eight tension band wire in a functional position. POSTOPERATIVE MANAGEMENT: Plaster of Paris cast with arthrodesis position of the affected finger and intrinsic plus position of at least one adjacent finger for 2 weeks, custom-made finger splint for 4 weeks. RESULTS: A total of 15 of 16 patients with an arthrodesis of the proximal interphalangeal finger joint of the dominant hand by tension band wire were followed up after an average of 31 months. None was affected by the arthrodesis in everyday live. All patients were very satisfied with the result. Nine of 15 patients were free of pain both at rest and with activity. The average DASH score was 48 points. Grip strength averaged 29 kg, 7 % stronger than the contralateral hand.
27275015 Abnormal PTPN11 enhancer methylation promotes rheumatoid arthritis fibroblast-like synovio 2016 May 19 The PTPN11 gene, encoding the tyrosine phosphatase SHP-2, is overexpressed in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) compared with osteoarthritis (OA) FLS and promotes RA FLS invasiveness. Here, we explored the molecular basis for PTPN11 overexpression in RA FLS and the role of SHP-2 in RA pathogenesis. Using computational methods, we identified a putative enhancer in PTPN11 intron 1, which contained a glucocorticoid receptor- binding (GR-binding) motif. This region displayed enhancer function in RA FLS and contained 2 hypermethylation sites in RA compared with OA FLS. RA FLS stimulation with the glucocorticoid dexamethasone induced GR binding to the enhancer and PTPN11 expression. Glucocorticoid responsiveness of PTPN11 was significantly higher in RA FLS than OA FLS and required the differentially methylated CpGs for full enhancer function. SHP-2 expression was enriched in the RA synovial lining, and heterozygous Ptpn11 deletion in radioresistant or innate immune cells attenuated K/BxN serum transfer arthritis in mice. Treatment with SHP-2 inhibitor 11a-1 reduced RA FLS migration and responsiveness to TNF and IL-1β stimulation and reduced arthritis severity in mice. Our findings demonstrate how abnormal epigenetic regulation of a pathogenic gene determines FLS behavior and demonstrate that targeting SHP-2 or the SHP-2 pathway could be a therapeutic strategy for RA.
27420799 Recurrent Bilateral Anterior Uveitis with Kikuchi-Fujimoto Disease. 2017 Dec PURPOSE: To report an uncommon case of Kikuchi-Fujimoto disease-associated-uveitis. METHODS: A 31-year-old Caucasian woman with cervical lymphadenitis and Kikuchi-Fujimoto disease recently confirmed by biopsy, complained about unilateral blurry vision. Differential diagnoses, including non-Hodgkin lymphoma, tuberculosis, sarcoidosis, Behçet disease, rheumatoid arthritis, and juvenile idiopathic arthritis was performed. We undertook a review of other similar cases found in the literature. RESULTS: Acute anterior unilateral uveitis was diagnosed, suffering from two recurrences of bilateral anterior uveitis. CONCLUSIONS: Additional reported cases are required to better understand the Kikuchi-Fujimoto disease and the pathogenesis and features of its ocular involvement.
26150125 Epidemiology research in rheumatology-progress and pitfalls. 2015 Nov Epidemiology research is a vital component of clinical studies in all medical fields. This Review provides a brief introduction to the methodology and interpretation of population and clinical epidemiology studies of musculoskeletal disorders. Data sources (including 'big data' and the issue of missing data), study design (cross-sectional, case-control and cohort studies, including clinical trial design) and the interpretation of study results are discussed with examples from the field of rheumatology, particularly using findings in patients with rheumatoid arthritis. Two or more treatments can be compared in clinical trials using a variety of study designs including superiority, noninferiority or equivalence. The different types of risk in epidemiological studies-absolute, attributable, background and relative-are important concepts in epidemiological research and their relative usefulness to clinicians and patients should be considered carefully. The potential pitfalls and challenges of generalizing the results of epidemiological studies to understanding disease aetiology and to clinical practice are also emphasized. The aim of the Review is to help readers to critically appraise published articles that use epidemiological designs or methods.
25561695 Comparison of psychological functioning in children and their mothers living through a lif 2016 Jun Childhood chronic illness is a potential source of distress and can be a traumatic experience both for the child and for the family. Several studies highlighted the importance of integrating psychosocial care and standard medical practice in the child's care. The current pilot study is the first investigation that compared distress in children and their mothers living through a life-threatening illness (cancer) and a non life-threatening (juvenile rheumatoid arthritis) chronic disease. Findings show that there are differences in the psychological functioning in children with respect to age. Moreover, the presence of posttraumatic stress symptoms in mothers of children with cancer seems to be a possible key to understanding the psychological response in this specific population.
26669765 Supplement of 5-hydroxytryptophan before induction suppresses inflammation and collagen-in 2015 Dec 15 BACKGROUND: Evidence is accumulating that a preclinical phase is present before the onset of clinical signs and symptoms of rheumatoid arthritis (RA). This phase represents an important therapeutic window within which interventions can dramatically modulate outcomes. An agent able to prevent RA for high risk individuals in this phase is therefore desired. In this study, we investigated whether tryptophan metabolite, 5-hydroxytryptophan (5-HTP) or 5-methoxytryptophan (5-MTP), can act as such an agent for primary prevention of collagen-induced arthritis (CIA). METHODS: Mouse splenocytes were pretreated with 5-HTP or 5-MTP and activated by anti-CD3 plus anti-CD28 antibodies in vitro. The percentages of interferon-γ (IFNγ)(+)CD4(+) T cells and interleukin-17 (IL-17)(+)CD4(+) T cells were measured by flow cytometry. The production of pro-inflammatory cytokines, serotonin and kynurenine was measured by enzyme-linked immunosorbent assay. A CIA model was used to investigate the in vivo effects of 5-HTP on the prevention of arthritis. RESULTS: 5-HTP decreased the percentages of IFNγ(+)CD4(+) T cells and IL-17(+)CD4(+) T cells and suppressed the production of IL-2, IL-4, IL-6, IL-17, tumor necrosis factor-α (TNFα) and IFNγ in activated splenocytes. 5-HTP administered before induction decreased the disease activities in CIA mice and suppressed the production of TNFα, IL-6 and cyclooxygenase-2 in arthritic joints. 5-HTP also increased serotonin, but decreased kynurenine in the CIA mice. CONCLUSIONS: 5-HTP suppresses inflammation and arthritis through decreasing the production of pro-inflammatory mediators. 5-HTP supplement before induction ameliorates arthritis in a CIA model.
27502297 β-Defensin 2 is a responsive biomarker of IL-17A-driven skin pathology in patients with p 2017 Mar BACKGROUND: IL-17A is a key driver of human autoimmune diseases, particularly psoriasis. OBJECTIVE: We sought to determine the role of IL-17A in psoriasis pathogenesis and to identify a robust and measurable biomarker of IL-17A-driven pathology. METHODS: We studied 8 healthy subjects and 8 patients with psoriasis before and after administration of secukinumab, a fully human anti-IL-17A mAb, and used a combination of classical techniques and a novel skin microperfusion assay to evaluate the expression of 170 proteins in blood, nonlesional skin, and lesional skin. For validation, we also tested stored sera from 601 patients with a variety of autoimmune diseases. RESULTS: IL-17A was specifically expressed in lesional compared with nonlesional psoriatic skin (9.8 vs 0.8 pg/mL, P < .001). Proteomic and gene transcription analyses revealed dysregulated antimicrobial peptides, proinflammatory cytokines, and neutrophil chemoattractants, levels of which returned to normal after treatment with secukinumab. β-Defensin 2 (BD-2) was identified as a biomarker of IL-17A-driven pathology by comparing protein expression in patients with psoriasis versus that in healthy subjects (5746 vs 82 pg/mL in serum, P < .0001; 2747 vs <218 pg/mL in dermis, P < .001), responsiveness to secukinumab therapy, and synergistic induction by IL-17A and TNF-α in epidermal keratinocytes. In a validation set of sera from 601 patients with autoimmune diseases thought to be IL-17A driven, we found that BD-2 levels are most highly increased in patients with psoriatic skin lesions, and in patients with psoriasis, BD-2 levels correlated well with IL-17A levels (r = 0.70, n = 199, P < .001) and Psoriasis Area and Severity Index scores (r = 0.53, n = 281, P < .001). CONCLUSION: IL-17A is a primary driver of skin pathology in patients with psoriasis, and serum BD-2 is an easily measurable biomarker of IL-17A-driven skin pathology.
27109049 Emu oil based nano-emulgel for topical delivery of curcumin. 2016 Jun 15 Curcumin and emu oil derived from emu bird (Dromaius novaehollandiae) has shown promising results against inflammation. However, the delivery of curcumin is hindered due to low solubility and poor permeation. In addition, till date the role of emu oil in drug delivery has not been explored systemically. Hence, the current investigation was designed to evaluate the anti-inflammatory potential of curcumin in combination with emu oil from a nanoemulgel formulation in experimental inflammation and arthritic in vivo models. Nanoemulsion was prepared using emu oil, Cremophor RH 40 and Labrafil M2125CS as oil phase, surfactant and co-surfactant. The optimized curcumin loaded nanoemulsion with emu oil was incorporated into carbopol gel for convenient application by topical route. The anti-inflammatory efficacy was evaluated in carrageenan induced paw edema and FCA induced arthritic rat model in terms of paw swelling, weight indices of the liver and spleen, pathological changes in nuclear factor kappa B, iNOS, COX-2 expression and inflammatory cytokines. Arthritic scoring, paw volume, biochemical, molecular, radiological and histological examinations indicated significant improvement in anti-inflammatory activity with formulations containing curcumin in combination with emu oil compared to pure curcumin. These encouraging results demonstrate the potential of formulations containing curcumin and emu oil combination in rheumatoid arthritis.
26315379 Fatigue in Primary Sjögren's Syndrome: Clinical, Laboratory, Psychometric, and Biologic A 2016 Jan OBJECTIVE: To identify independent contributors of fatigue in primary Sjögren's syndrome (SS) patients, taking into account clinical, laboratory, and psychological features, and to explore the potential role of interferon (IFN)-induced gene indoleamine 2,3-dioxygenase (IDO-1), anti-21-hydroxylase (anti-21[OH]) antibodies, and soluble BAFF. METHODS: Detailed clinical and laboratory characteristics were recorded for 106 primary SS patients. The Functional Assessment of Chronic Illness Therapy-Fatigue, Zung Depression Scale, State-Trait Anxiety Inventory, Eysenck Personality Questionnaire Scale, and Athens Insomnia Scale were adopted to assess fatigue, depression, anxiety, and sleep disturbances, respectively. Peripheral whole blood expression levels of IDO-1, as well as type I and II IFN-induced genes were calculated using quantitative reverse transcriptase-polymerase chain reaction. Serum anti-21(OH) antibodies and soluble BAFF levels were determined by a radioimmunoassay and an enzyme-linked immunosorbent assay, respectively. Univariate and multivariate models were performed to identify determinants of fatigue. RESULTS: Fatigue was detected in 32 of 106 (30.2%) primary SS patients. In univariate analysis, fatigue was associated with arthralgias/myalgias, fibromyalgia hydroxychloroquine therapy, both state and trait anxiety scores, depression, and neuroticism, as well as impaired sleep patterns. Multivariate analysis revealed neuroticism (odds ratio [OR] 6.9, [95% confidence interval (95% CI) 1.7-28.0]), depression (OR 3.0 [95% CI 0.8-11.0]), and fibromyalgia (OR 5.5 [95% CI 1.1-27.7]) as independent fatigue contributors. Soluble BAFF levels, anti-21(OH) autoantibodies, and IDO-1 messenger RNA expression did not significantly differ between fatigued and nonfatigued primary SS patients. CONCLUSION: Depression, neuroticism, and fibromyalgia play a major role in primary SS-associated fatigue and should be addressed in clinical practice, with active collaboration between rheumatologists and mental health professionals. Further studies are warranted in order to explore underlying pathophysiologic pathways that might explain fatigue in the setting of primary SS.
27687482 The IL-20 receptor axis in immune-mediated inflammatory arthritis: novel links between inn 2016 Aug The treatment of rheumatoid arthritis (RA) and spondyloarthritis (SpA) was transformed a little over a decade ago by the introduction of agents neutralizing the pro-inflammatory cytokine tumour necrosis factor (TNF)-α. Nevertheless, some patients do not achieve remission and the inhibition of the normal immune system with current drugs increases the risk of infection. The interleukin (IL)-20 receptor (IL-20R) axis is pivotal for tissue homeostasis. By contrast, this axis does not seem to directly activate cells of the immune system. Thus, modulation of the IL-20R axis might not result in increased risk of infection. The IL-20R axis consists of the three cytokines IL-19, IL-20, and IL-24 (termed the IL-20R cytokines) and their shared receptors. All three cytokines bind the receptor complex of IL-20R2/IL-20R1 whereas only IL-20 and IL-24 also bind the receptor complex of IL-20R2/IL-22R1. This short review describes how the IL-20R axis could be a novel link between innate immune recognition and bone homeostasis. The IL-20R cytokines are produced in response to both danger-associated molecular patterns and immune complexes formed by RA-associated autoantibodies. This could be of importance because these mediators can thus be present even in situations without inflammation. IL-19 shows anti-inflammatory properties in arthritis through IL-20R1. IL-20 and IL-24 through IL-22R seem to participate in the recruitment of mononuclear cells to the synovial joint and to sites of bone erosion in particular. Our results indicate that dual inhibition of IL-20 and IL-24 or attenuation of the shared IL-22R subunit could have a beneficial effect on radiographic progression, especially in seropositive RA.
25595700 Dietary supplementation with arachidonic acid increases arachidonic acid content in paw, b 2015 Jan 16 BACKGROUND: Arachidonic acid (ARA) is an essential fatty acid and a major constituent of biomembranes. It is converted into various lipid mediators, such as prostaglandin E2 (PGE2), which is involved in the development of rheumatoid arthritis (RA). However, the effects of dietary ARA on RA are unclear. Our objective was to clarify the effects of dietary ARA on an experimental rat arthritis model. METHODS: Lew rats were fed three contents of ARA diet (0.07%, 0.15% or 0.32% ARA in diet (w/w)), a docosahexaenoic acid (DHA) diet (0.32% DHA), or a control diet. After 4 weeks, arthritis was induced by injection of Freund's complete adjuvant into the hind footpad. We observed the development of arthritis for another 4 weeks, and evaluated arthritis severity, fatty acid and lipid mediator contents in the paw, and expression of genes related to lipid mediator formation and inflammatory cytokines. Treatment with indomethacin was also evaluated. RESULTS: The ARA content of phospholipids in the paw was significantly elevated with dietary ARA in a dose-dependent manner. Dietary ARA as well as DHA did not affect arthritis severity (paw edema, arthritis score, and bone erosion). PGE2 content in the paw was increased by arthritis induction, but was not modified by dietary ARA. Dietary ARA did not affect the contents of other lipid mediators and gene expression of cyclooxygenase (COX)-1, COX-2, lipoxgenases and inflammatory cytokines. Indomethacin suppressed arthritis severity and PGE2 content in the paw. CONCLUSION: These results suggest that dietary ARA increases ARA content in the paw, but has no effect on arthritis severity and PGE2 content of the paw in a rat arthritis model.
27857506 Short- to mid-term results of ulna head replacement as both a primary and revision implant 2016 Oct We present the results of short- to medium-term follow-up of 10 patients following ulna head replacement. The mean age of patients was 63.2 years (range 48-81 years), with the mean duration of follow-up being 48 months (12-88 months). The indications for the procedure were primary osteoarthritis (n = 3), post-traumatic osteoarthritis (n = 4), failed Darrach's procedure (n = 2) and rheumatoid arthritis (n = 1). Two patients required revision (20%), one for gross aseptic loosening of the stem and another for an initially oversized head. At final follow-up, the satisfactory rate was 90%. The mean VAS score was 2.4 (range 0-8). The average DASH score was 37 (range 0-72.5). Our study suggests that ulna head replacement can give satisfactory forearm function; however, concerns exist regarding bone resorption and tapering around the prosthesis, which may affect the long-term performance of the prosthesis. LEVEL OF EVIDENCE: IV.
27679792 "The NET Outcome": Are Neutrophil Extracellular Traps of Any Relevance to the Pathophysiol 2016 Neutrophil extracellular trap (NET) formation represents a form of cell death distinct from apoptosis or necrosis, by which invading pathogens are simultaneously entangled and potentially eliminated. Increased NET formation is observed in systemic lupus erythematosus (SLE), rheumatoid arthritis, antineutrophil cytoplasmic antibody-associated small vessel vasculitis, antiphospholipid antibody syndrome (APS), and psoriasis. NETs contribute to the pathogenesis of autoimmunity by exposing cryptic autoepitopes, which may facilitate the generation of autoantibodies, induce the production of interferons, and activate the complement cascade. In SLE, augmented disease activity and renal disease are associated with increased NET formation, so that NETs could serve as a marker for the monitoring of disease activity. NETs can additionally cause endothelial cell damage and death and stimulate inflammation in atheromatous plaques, adding to the accelerated atherosclerosis witnessed in autoimmune disease. Since NETs induce production of interferons, assessing the extent of NET formation might facilitate the prediction of IFN-alpha levels and identification of SLE patients with presumably better responses to anti-IFN-alpha therapies or other novel therapeutic concepts, such as N-acetyl-cysteine and inhibitors of DNase 1 and peptidylarginine deiminase 4 (PAD4), which also target NETs. In summary, the study of NETs provides a novel approach to the understanding of autoimmune disease pathogenesis in childhood and opens new vistas in the development of sensitive disease markers and targeted therapies.