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ID PMID Title PublicationDate abstract
26583367 Recommendations of the ESSR Arthritis Subcommittee for the Use of Magnetic Resonance Imagi 2015 Sep This article presents the recommendations of the European Society of Musculoskeletal Radiology Arthritis Subcommittee regarding the standards of the use of MRI in the diagnosis of musculoskeletal rheumatic diseases. The recommendations discuss (1) the role of MRI in current classification criteria of musculoskeletal rheumatic diseases (including early diagnosis of inflammation, disease follow-up, and identification of disease complications); (2) the impact of MRI on the diagnosis of axial and peripheral spondyloarthritis, rheumatoid arthritis, and juvenile spondyloarthritis; (3) MRI protocols for the axial and peripheral joints; (4) MRI interpretation and reporting for axial and peripheral joints; and finally, (5) methods for assessing MR images including quantitative, semiquantitative, and dynamic contrast-enhanced MRI studies.
26445771 Effects of Dairy Products Consumption on Health: Benefits and Beliefs--A Commentary from t 2016 Jan Dairy products provide a package of essential nutrients that is difficult to obtain in low-dairy or dairy-free diets, and for many people it is not possible to achieve recommended daily calcium intakes with a dairy-free diet. Despite the established benefits for bone health, some people avoid dairy in their diet due to beliefs that dairy may be detrimental to health, especially in those with weight management issues, lactose intolerance, osteoarthritis, rheumatoid arthritis, or trying to avoid cardiovascular disease. This review provides information for health professionals to enable them to help their patients make informed decisions about consuming dairy products as part of a balanced diet. There may be a weak association between dairy consumption and a possible small weight reduction, with decreases in fat mass and waist circumference and increases in lean body mass. Lactose intolerant individuals may not need to completely eliminate dairy products from their diet, as both yogurt and hard cheese are well tolerated. Among people with arthritis, there is no evidence for a benefit to avoid dairy consumption. Dairy products do not increase the risk of cardiovascular disease, particularly if low fat. Intake of up to three servings of dairy products per day appears to be safe and may confer a favourable benefit with regard to bone health.
26213566 Crude triterpenoid saponins from Anemone flaccida (Di Wu) exert anti-arthritic effects on 2015 BACKGROUND: Anemone flaccida Fr . Schmidt (Ranunculaceae) (Di Wu in Chinese) is used to treat punch injury and rheumatoid arthritis (RA). However, the active compounds and underlying mechanism of action mediating the anti-arthritic effects of A. flaccida remain unclear. This study aims to evaluate the underlying action mechanism of A. flaccida crude triterpenoid saponins (AFS) on RA using a type II collagen (CII)-induced arthritis (CIA) rat model, and to assess the anti-inflammatory effects of the main active compounds of AFS, namely flaccidoside II, anhuienoside E, glycoside St-I4a, hemsgiganoside B, hederasaponin B, and 3-O-α-l-rhamnopyranosyl (1 → 2)-β-d-glucopyranosyl oleanolic acid 28-O-β-d-glucopyranosyl (1 → 6)-β-d-glucopyranosyl ester. METHODS: Male Wistar rats (n = 50) were randomly separated into five groups (n = 10) and immunized by CII injection. AFS (200 or 400 mg/kg) and dexamethasone were orally administered for 30 days after establishing the model. The arthritis severity was assessed by paw volume using a plethysmometer. After 30 days of treatment, the right hind paws of the rats were obtained. Paw histology was analyzed by hematoxylin and eosin staining, and radiologic imaging was performed by micro-computed tomography. MTT assays were used to evaluate the cytotoxicity of AFS and its main compounds in RAW264.7 cells. Enzyme-linked immunosorbent assay kits were used to measure interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum and supernatants from AFS- and main AFS compound-treated RAW264.7 cells stimulated by lipopolysaccharide (LPS). RESULTS: Anemone flaccida crude triterpenoid saponins inhibited redness and swelling of the right hind paw in the CIA model. Radiological and histological examinations indicated that inflammatory responses were reduced by AFS treatment. Moreover, comparing with untreated rats, serum TNF-α (P = 0.0035 and P < 0.001) and IL-6 (P = 0.0058 and P = 0.0087) were lower in AFS-treated CIA rats at the dose of 200 and 400 mg/kg/day. AFS and its main compounds, including hederasaponin B, flaccidoside II, and hemsgiganoside B, significantly inhibited TNF-α (P = 0.0022, P = 0.013, P = 0.0015, and P = 0.016) and IL-6 (P = 0.0175, P < 0.001, P < 0.001, and P < 0.001) production in LPS-treated RAW264.7 cells, respectively. CONCLUSIONS: Anemone flaccida crude triterpenoid saponins and its main bioactive components, including hederasaponin B, flaccidoside II, and hemsgiganoside B, decreased pro-inflammatory cytokine levels in a CIA rat model and LPS-induced RAW264.7 cells.
27496243 Development and initial cohort validation of the Arthritis Research UK Musculoskeletal Hea 2016 Aug 5 OBJECTIVES: Current musculoskeletal outcome tools are fragmented across different healthcare settings and conditions. Our objectives were to develop and validate a single musculoskeletal outcome measure for use throughout the pathway and patients with different musculoskeletal conditions: the Arthritis Research UK Musculoskeletal Health Questionnaire (MSK-HQ). SETTING: A consensus workshop with stakeholders from across the musculoskeletal community, workshops and individual interviews with a broad mix of musculoskeletal patients identified and prioritised outcomes for MSK-HQ inclusion. Initial psychometric validation was conducted in four cohorts from community physiotherapy, and secondary care orthopaedic hip, knee and shoulder clinics. PARTICIPANTS: Stakeholders (n=29) included primary care, physiotherapy, orthopaedic and rheumatology patients (n=8); general practitioners, physiotherapists, orthopaedists, rheumatologists and pain specialists (n=7), patient and professional national body representatives (n=10), and researchers (n=4). The four validation cohorts included 570 participants (n=210 physiotherapy, n=150 hip, n=150 knee, n=60 shoulder patients). OUTCOME MEASURES: Outcomes included the MSK-HQ's acceptability, feasibility, comprehension, readability and responder burden. The validation cohort outcomes were the MSK-HQ's completion rate, test-retest reliability and convergent validity with reference standards (EQ-5D-5L, Oxford Hip, Knee, Shoulder Scores, and the Keele MSK-PROM). RESULTS: Musculoskeletal domains prioritised were pain severity, physical function, work interference, social interference, sleep, fatigue, emotional health, physical activity, independence, understanding, confidence to self-manage and overall impact. Patients reported MSK-HQ items to be 'highly relevant' and 'easy to understand'. Completion rates were high (94.2%), with scores normally distributed, and no floor/ceiling effects. Test-retest reliability was excellent, and convergent validity was strong (correlations 0.81-0.88). CONCLUSIONS: A new musculoskeletal outcome measure has been developed through a coproduction process with patients to capture prioritised outcomes for use throughout the pathway and with different musculoskeletal conditions. Four validation cohorts found that the MSK-HQ had high completion rates, excellent test-retest reliability and strong convergent validity with reference standards. Further validation studies are ongoing, including a cohort with rheumatoid/inflammatory arthritis.
27829671 Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases. 2017 Jan Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis (RA). Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of RA. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as RA, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs, and the role of adenosine in fibrosis and fibrosing diseases is also discussed.
27276803 [EFFECTIVENESS OF SLIDING OSTEOTOMY FOR CORRECTING SEVERE VALGUS DEFORMITY IN TOTAL KNEE A 2016 Feb OBJECTIVE: To explore the surgical technique and effectiveness of sliding osteotomy of medial femur condyle in handling soft tissue balance of severe valgus deformity in total knee arthroplasty (TKA). METHODS: Between June 2008 and February 2014, 18 cases (19 knees) of severe valgus knees undergoing sliding osteotomy of medial femur condyle in primary TKA were included, Of the 18 patients, 6 were male and 12 were female with an average age of 52.3 years (range, 29-72 years), including 3 cases (3 knees) of osteoarthritis, 11 cases (12 knees) of rheumatoid arthritis, 3 cases (3 knees) of post-traumatic arthritis, and 1 case (1 knee) of deformities in skeletal dysplasia. Before surgery, the tibial femur angle (TFA) was (33.0 +/- 2.9) degrees; the Hospital for Special Surgery (HSS) score was 41.6 +/- 7.7; the Knee Society Score (KSS) lateral stability score was 6.0 +/- 5.4. All cases wererated as type II according to Krackow classification of valgus knee. During primary TKA, sliding osteotomy of medial femur condyle was performed via a medial parapatellar approach. RESULTS: Incision healed by first intention in all cases. Peroneal nerve palsy occurred in 1 patient, which was cured after 6 months of conservative treatment. Eighteen cases were followed up 19 months to 7 years, with an average of 5.7 years. All patients had no complications of deep vein thrombosis, deep infection, and prosthesis loosening. X-ray films showed that bone healing was achieved in all cases at 6 months. At last follow-up, the TFA was (4.8 +/- 1.8) degrees, showing significant difference when compared with preoperative value (t=62.61, P=0.00). The HSS score was 87.2 +/- 10.5 and the KSS lateral stability score was 12.4 +/- 3.1, all showing significant differences when compared with preoperative scores (t = -33.35, P=0.00; t = -6.83, P=0.00). CONCLUSION: Sliding osteotomy of medial femur condyle is effective for correcting severe valgus knee deformity during TKA. Satisfactory joint function and stability may be achieved
25979422 The Autoimmunity-Associated Gene CLEC16A Modulates Thymic Epithelial Cell Autophagy and Al 2015 May 19 CLEC16A variation has been associated with multiple immune-mediated diseases, including type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, celiac disease, Crohn's disease, Addison's disease, primary biliary cirrhosis, rheumatoid arthritis, juvenile idiopathic arthritis, and alopecia areata. Despite strong genetic evidence implicating CLEC16A in autoimmunity, this gene's broad association with disease remains unexplained. We generated Clec16a knock-down (KD) mice in the nonobese diabetic (NOD) model for type 1 diabetes and found that Clec16a silencing protected against autoimmunity. Disease protection was attributable to T cell hyporeactivity, which was secondary to changes in thymic epithelial cell (TEC) stimuli that drive thymocyte selection. Our data indicate that T cell selection and reactivity were impacted by Clec16a variation in thymic epithelium owing to Clec16a's role in TEC autophagy. These findings provide a functional link between human CLEC16A variation and the immune dysregulation that underlies the risk of autoimmunity.
25455683 Cardiovascular events in ankylosing spondylitis: an updated meta-analysis. 2015 Apr OBJECTIVES: Rheumatoid arthritis is associated with increased cardiovascular risk. In the guidelines, ankylosing spondylitis (AS) is considered to have an equally high cardiovascular risk. The literature findings remain controversial. This study aims to assess the risk of myocardial infarction (MI) and stroke in AS patients. METHODS: An updated meta-analysis with a new systematic literature review using PubMed was conducted up to January 2014. Incidence of MI or stroke was calculated by metaproportion. RESULTS: In addition to the 11 previously included studies, six new studies assessed the occurrence of MI or stroke in AS patients. (1) MI. A total of 2131 MI were reported in AS patients (n = 27,532) over a mean follow-up of 15 years: incidence 5.3% (1.6%-11.0%), i.e., 0.36/100 pyrs. Seven studies revealed 17,410 MI [2.5% (95% CI: 1.8%-3.4%)] in the control group (n = 1,349,964). Meta-analysis of the seven longitudinal studies showed a significant increase in MI [OR = 1.60 (95% CI: 1.32-1.93)] in AS patients. (2) Stroke. In 11 longitudinal studies (n = 51,990), 1807 strokes were reported in AS patients over 17.6 years of follow-up: incidence 3.6% (1.5%-6.5%), i.e., 0.24/100 pyrs. Three studies reported 22,899 strokes in controls (n = 1,239,041), giving an incidence of 1.78% (1.75%-1.80%). A significant increase in stroke [OR = 1.50 (95% CI: 1.39-1.62)] in AS patients was found. CONCLUSION: AS patients appear to have a higher risk of MI and stroke. Management of cardiovascular risk factors and control of systemic inflammation should be taken into account in AS to decrease this high cardiovascular risk.
27729087 Familial risk of systemic sclerosis and co-aggregation of autoimmune diseases in affected 2016 Oct 12 BACKGROUND: Systemic sclerosis (SSc) is a rare and devastating disease affecting skin and internal organs. Familial aggregation of SSc and co-aggregation with other autoimmune diseases is rarely reported. METHODS: We identified 23,658,577 beneficiaries registered with the National Health Insurance database in 2010, 1891 of whom had SSc. We identified 21,009,551 parent-child relationships and 17,168,340 full sibling pairs. The familial risks of SSc and other autoimmune diseases and familial transmission were estimated. RESULTS: The prevalence of SSc in the general population was 0.008 %. There are 3801 individuals had at least one first-degree relative with SSc, among them 3 people had SSc which was equivalent to a prevalence of 0.08 %. The adjusted relative risk (RR) (95 % CI) for SSc was 81.21 (11.40-579.72) for siblings of SSc patients. The familial transmission (genetic plus shared environmental contribution to total phenotypic variance of SSc) was 0.72. However, 84.1 % of patients were expected to be sporadic cases. The RR (95 % CI) in first-degree relatives of SSc patients was 2.64 (1.46-4.75) for rheumatoid arthritis, 6.51 (4.05-10.46) for systemic lupus erythematosus, 2.77 (1.04-7.35) for Sjögren's syndrome, 8.05 (2.03-31.92) for idiopathic inflammatory myositis, and 1.52 (1.15-2.01) for psoriasis. CONCLUSIONS: The risks of SSc and other autoimmune diseases are increased in relatives of people with SSc, and family factors explain over two-thirds of the phenotypic variance of the disease. These findings may be useful in counselling families of patients with SSc and for further genetic studies.
26297637 Safety assessment of saponins extract in Dolichos falcatus Klein: Subchronic study in Spra 2015 Nov 4 ETHNOPHARMACOLOGICAL RELEVANCE: Dolichos falcatus Klein (DF), a Chinese Dai ethnic medicine popularly known as "Tuoyeteng" in Yunnan province of China, has been widely used in China to treat fracture, rheumatoid arthritis and soft tissue injuries for a long time. Our previous study showed that saponins in DF (DFS) ameliorated the gouty arthritis induced by MSU crystals in vivo and in vitro. The present study was carried out to evaluate the no-observed-adverse-effect level (NOAEL) of DFS. MATERIALS AND METHODS: Sprague-Dawley rats (10/sex/group) were gavaged with DFS at dose level of 0, 50, 100 and 200 mg/kg body weight /day for 90-days. RESULTS: DFS administration did not result in mortality or show treatment-related changes in clinical signs of toxicity, body weights gain or feed consumption. Similarly, in addition to slightly hemolytic anemia and gastrointestinal tract lesion in males of high-dose treatment group, no toxicologically significant treatment-related changes in hematological, clinical chemistry, urine analysis parameters, organ weights, and macroscopic and microscopic abnormalities were noted during the testing period. CONCLUSION: The results of subchronic toxicity study support the NOAEL for DFS as 200 mg/kg/d in females and as 100mg/kg/d in males. These results provide an important reference for further DFS-related clinical trials or new drug exploration.
26146463 Therapeutic Potential of IL-17-Mediated Signaling Pathway in Autoimmune Liver Diseases. 2015 Emerging evidence reveals that various cytokines and tissue microenvironments contribute to liver inflammation and autoimmunity, and IL-17 family is one of highlights acknowledged. Although the implication of IL-17 family in most common autoimmune diseases (such as psoriasis, inflammatory bowel disease, and rheumatoid arthritis) has been extensively characterized, the role of this critical family in pathophysiology of autoimmune liver diseases (AILD) still needs to be clarified. In the review, we look into the intriguing biology of IL-17 family and further dissect on the intricate role of IL-17-mediated pathway in AILD. Considering encouraging data from preclinical and clinical trials, IL-17 targeted therapy has shown promises in several certain autoimmune conditions. However, blocking IL-17-mediated pathway is just beginning, and more fully investigation and reflection are required. Taking together, targeting IL-17-mediated responses may open up new areas of potential clinical treatment for AILD.
26005048 Inflammasomes and human autoimmunity: A comprehensive review. 2015 Jul Inflammasomes are multi-protein complexes composed of a NOD-like receptor (NLR)/an AIM-like receptor (ALR), the adapter molecule apoptosis-associated speck-like protein that contains a CARD (ASC), and caspase-1. Active caspase-1 cleaves pro-IL-1β and pro-IL-18 to IL-1β and IL-18, resulting in inflammation. Genetic mutations in inflammasomes were first recognized to result in autoinflammatory diseases, which are characterized by the absence of both autoantibodies and autoreactive-T/B cells. However, there is increasing attention being placed on genetic polymorphisms that are involved in the components of inflammasomes, and these have implications for innate immunity and the natural history of autoimmune diseases. For example, while the NOD-like receptor family, pyrin domain containing 1 (NLRP1) haplotypes contributes to susceptibility to developing vitiligo; there are other single nucleotide polymorphisms (SNPs) that alters the susceptibility and severity of rheumatoid arthritis (RA) and juvenile idiopathic arthritis. Indeed, there are multiple factors that contribute to lowering the threshold of immunity and inflammasomes play a key role in this threshold. For example, IL-1β and IL-18 further perpetuate Th17 responses and endothelial cell damage, which potentiate a number of autoimmune diseases, including synovitis in RA, cardiovascular disease, and systemic lupus erythematosus (SLE). There is also increasing data on the role of innate immunity in experimental autoimmune encephalomyelitis (EAE), in lupus nephritis, and in a variety of autoimmune pathologies in which activation of the innate immune system is the driver for the adaptive system. Indeed, it is likely that the chronic pathology of autoimmunity is mediated in part by otherwise innocent bystander cells, augmented by inflammasomes.
27614825 Bilateral Arthrodesis of the Ankle Joint: Self-Reported Outcomes in 35 Patients From the 2016 Nov Bilateral ankle arthrodesis is seldom performed, and results concerning the outcome and satisfaction can only sparsely be found in published studies. We analyzed the data from 35 patients who had undergone bilateral ankle arthrodesis in the Swedish Ankle Registry using patient-reported generic and region-specific outcome measures. Of 36 talocrural arthrodeses and 34 tibio-talar-calcaneal arthrodeses, 6 ankles (9%) had undergone repeat arthrodesis because of nonunion. After a mean follow-up period of 47 ± 5 (range 12 to 194) months, the mean scores were as follows: self-reported foot and ankle score, 33 ± 10 (range 4 to 48); the EuroQol Group's EQ-5D(™) score, 0.67 ± 0.28 (range -0.11 to 1), the EuroQol Group's visual analog scale score, 70 ± 19 (range 20 to 95), 36-item Short Form Health Survey (SF-36) physical domain, 39 ± 11 (range 16 to 58); and SF-36 mental domain, 54 ± 14 (range 17 to 71). Patients with rheumatoid arthritis seemed to have similar self-reported foot and ankle scores but possibly lower EQ-5D(™) and SF-36 scores. Those with talocrural arthrodeses scored higher than did those with tibio-talar-calcaneal arthrodeses on the EQ5D(™) and SF-36 questionnaires (p = .03 and p = .04). In 64 of 70 ankles (91%), the patients were satisfied or very satisfied with the outcome. In conclusion, we consider bilateral ankle arthrodesis to be a reasonable treatment for symptomatic hindfoot arthritis, with high postoperative mid-term satisfaction and satisfactory scores on the patient-reported generic and region-specific outcome measures, when no other treatment option is available.
27234527 Epigallocatechin gallate inhibits urate crystals-induced peritoneal inflammation in C57BL/ 2016 Oct Gouty arthritis is a type of monosodium urate (MSU) crystals-induced inflammation in the articular tissue and shows the increased levels of neutrophil infiltration and IL-1β secretion. MSU is capable of activating IL-1β through a nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Epigallocatechin gallate (EGCG), a bioactive polyphenol in green tea with potent antioxidant activity, is effective to prevent rheumatoid arthritis and osteoarthritis. However, it remains unclear whether EGCG improves gouty inflammation. This study aimed to investigate the effect of EGCG on MSU-induced inflammation and NLRP3 inflammasome activation. C57BL/6 mice were received subcutaneous injection or oral gavage of EGCG before the intraperitoneal injection of MSU. The results demonstrated that EGCG inhibited MSU-induced neutrophil infiltration and IL-1β secretion. Furthermore, EGCG decreased MSU-triggered neutrophil cytosolic factor 1 and NLRP3 protein expression, limiting pro-inflammatory mediator secretion such as IL-1β, IL-6, monocyte chemoattractant protein-1, and serum amyloid A. In addition, EGCG treatment suppressed NLRP3 inflammasome activation in MSU-challenged THP-1 monocytes. These findings indicate that EGCG treatment ameliorates MSU-induced inflammation, suggesting that EGCG exerts anti-inflammatory effect against MSU-induced acute gout attack.
25836258 Association between ankylosing spondylitis and the miR-146a and miR-499 polymorphisms. 2015 miRNAs are small, non-coding RNAs that regulate the expression of multiple target genes at the post-transcriptional level. Single-nucleotide polymorphisms (SNPs) in miRNA sequences may alter miRNA expression and have been implicated in the pathogenesis of multiple forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis. The present study explored the association between ankylosing spondylitis (AS) and two single nucleotide polymorphisms (SNPs), miR-146a rs2910164G>C and miR-499 rs3746444T>C, in a Han Chinese population. A case-control study consisting of 102 subjects with AS and 105 healthy controls was designed. The two miRNA SNPs were identified by direct sequencing. Subsequently, their gene and genotype frequencies were compared with healthy controls. A significant difference was observed in the miR-146a rs2910164G>C SNP. The frequency of the G allele was markedly higher in the AS patients than in the healthy controls (P = 0.005, Pc = 0.01, OR = 1.787), and the frequency of the GG genotype was higher in AS patients than in controls (P = 0.014, Pc = 0.042, OR = 2.516). However, no significant association was found between the miR-499 rs3746444T>C variant and susceptibility to AS. This is the first study to address the association between the miR-146a rs2910164G>C and miR-499 rs3746444T>C polymorphisms and AS, and it suggests a potential pathogenic factor for AS. Further studies are needed to validate our findings in a larger series, as well as in other ethnic backgrounds.
26422240 Pyrocarbon Proximal Interphalangeal Joint Arthroplasty: Minimum Five-Year Follow-Up. 2015 Nov PURPOSE: To report the outcomes, complications, and survivorship of pyrocarbon proximal interphalangeal joint arthroplasty at a minimum of 5-year follow-up. METHODS: A review of 97 implants in 72 consecutive patients from our joint arthroplasty database was undertaken. Patient demographics, complications, further surgery, and implant revision were recorded. Objective outcome was assessed by grip strength, range of motion, and radiological assessment of alignment, loosening, and subsidence. Subjective outcome was assessed by Patient Evaluation Measure; Quick Disabilities of the Arm, Shoulder, and Hand score; and visual analog scores (0, best; 10, worst) for appearance, satisfaction, and pain. RESULTS: Diagnosis was osteoarthritis in 60 joints, rheumatoid arthritis in 12 joints, psoriatic arthritis in 11 joints, and trauma in 14 joints. The average follow-up was 118 months (range, 60-164 months). The mean arc of motion was 35° (range, 0° to 90°). There was no difference in grip strength between operated and nonoperated side. Of the 97 implants, 36 required additional surgery, of which 14 were revised and 22 required reconstruction around a retained implant. The average Patient Evaluation Measure and Quick Disabilities of the Arm, Shoulder and Hand scores were 33 (range, 10-69) and 35 (range, 0-93), respectively. Mean visual analog scores for pain, satisfaction, and appearance were 2 (range, 0-8), 7 (0-10), and 8 (0-10), respectively. All implants had a lucent line with nearly all classified as either Herren grade 2 or 3. Progressive loosening was seen in 48% of implants. Implant survival as assessed by Kaplan-Meier was 85% at both 5 and 10 years. CONCLUSIONS: Good pain relief and maintenance of preoperative arc of motion was achieved with no major deterioration over time. Most implant revisions were performed within 24 months of the index procedure. Currently progressive loosening was not translated into revision surgery. Implant revision rate was higher than with other prostheses. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.
25057181 CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis. 2015 Dec OBJECTIVES: Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA. METHODS: A genetic association study was performed in 639 JIA patients and 1613 healthy controls of northwest European descent. Ninety-three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene approach. Results of the entire JIA patient group (all subtypes) were compared with results obtained, alternatively, with a clinically homogeneous patient group including only oligoarticular and rheumatoid factor (RF) negative polyarticular JIA patients (n=493). Meta-analyses were performed for all SNPs that have been typed in other Caucasian JIA cohorts before. RESULTS: SNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (p<0.05), strengthening the evidence for involvement of these genes in JIA. In the majority of these replicated SNPs, effect sizes were larger when analysing a homogeneous patient cohort than when analysing all subtypes. We identified two novel associations with oligoarticular and RF-negative polyarticular JIA: CD226 rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29, 95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR 1.18, p=0.001, for rs763361 and rs1980422, respectively). CONCLUSIONS: The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.
27966604 Endogenous programmed death ligand-1 restrains the development and onset of Sjӧgren's syn 2016 Dec 14 Programmed death-ligand 1 (PD-L1) down-modulates various immune responses by engaging the co-inhibitory receptor programmed death-1. Expression of PD-L1 and programmed death-1 is elevated in the salivary glands of patients with Sjögren's syndrome (SS). The objective of this study is to define the role of endogenous PD-L1 in SS pathogenesis in non-obese diabetic (NOD) mouse model of this disease. We inhibited endogenous PD-L1 function by intraperitoneal administration of a blocking antibody to 6 week-old female NOD/ShiLtJ mice repeatedly during a 9-day period. PD-L1 blockade accelerated leukocyte infiltration and caspase-3 activation in the submandibular gland (SMG), production of antinuclear and anti-M3 muscarinic acetylcholine receptor (M3R) autoantibodies and impairment of saliva secretion, indicative of accelerated development and onset of SS. The effect of PD-L1 blockade was associated with increased T- and B cells and T helper 1 cytokine IFN-γ in the SMG. Local administration of exogenous IFN-γ to the SMG led to impaired salivary secretion accompanied by down-regulation of aquaporin 5 and an increase in anti-M3R autoantibodies. Conversely, neutralization of IFN-γ markedly improved salivary secretion and aquaporin 5 expression in anti-PD-L1-treated NOD/ShiLtJ mice. Hence, endogenous PD-L1 hinders the development and onset of SS in NOD mice, in part by suppressing IFN-γ production.
27749218 Serum calprotectin is a biomarker of carotid atherosclerosis in patients with primary Sjö 2016 Nov OBJECTIVES: We aimed to identify the association of carotid atherosclerosis with the traditional risk factors, disease features, cytokine profile, and calprotectin in patients with primary Sjögren's syndrome (pSS). METHODS: 63 primary pSS patients and 63 age- and sex-matched healthy controls underwent carotid ultrasound, clinical and laboratory examination. The presence of carotid plaques was taken as carotid atherosclerosis. The covariates of carotid atherosclerosis were identified in univariate and multivariate regressions. RESULTS: Patients with pSS had higher prevalence of carotid atherosclerosis (13% vs. 2%, p<0.05) and higher serum levels of calprotectin, tumour necrosis factor receptor 2 (TNF-R2), hepatocyte growth factor (HGF), and monocyte chemoattractant protein-1 (MCP-1) than controls. Sex, menopause, and the prevalence of traditional cardiovascular did not differ between groups (all p>0.05). In univariate analyses, serum calprotectin, most traditional cardiovascular (age, male sex, metabolic syndrome, hypertension, hypertriglyceridaemia, and serum creatinine), and some disease-associated risk factors (glucocorticoid or saliva substitute use, constitutional domain of Eular-Sjögren's syndrome disease activity index - EULAR) were associated with a higher risk for plaque. In a multivariate analysis, having pSS and higher serum calprotectin were associated with carotid atherosclerosis independent of traditional risk factors. CONCLUSIONS: pSS have a higher prevalence of carotid atherosclerosis, which is associated with higher serum calprotectin level independent of traditional cardiovascular risk factors. Our findings suggest calprotectin as a biomarker of subclinical atherosclerosis in pSS.
26338037 Germline variation of TNFAIP3 in primary Sjögren's syndrome-associated lymphoma. 2016 Apr BACKGROUND AND OBJECTIVE: A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association. PATIENTS AND METHODS: The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts. RESULTS: The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively). CONCLUSIONS: This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.