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ID PMID Title PublicationDate abstract
26731521 Automatic Quantification of Radiographic Finger Joint Space Width of Patients With Early R 2016 Oct The assessment of joint space width (JSW) on hand X-ray images of patients suffering from rheumatoid arthritis (RA) is a time-consuming task. Manual assessment is semiquantitative and is observer dependent which hinders an accurate evaluation of joint damage, particularly in the early stages. Automated analysis of the JSW is an important step forward since it is observer independent and might improve the assessment sensitivity in the early RA stage. This study proposes a fully automatic method for both joint location and margin detection in RA hand radiographs. The location detection procedure is based on image features of the joint region and is aided by geometric relationship of finger joints. More than 99% of joint locations are detected with an error smaller than 3 mm with respect to the manually indicated gold standard. The joint margins are detected by combining intensity values and spatially constrained intensity derivatives, refined by an active contour model. More than 96% of the joints are successfully delineated. The JSW is calculated over the middle 60% of a landmark-defined joint span. The overall JSW error compared with the ground truth is 6.8%. In conclusion, the proposed method is able to automatically locate the finger joints in RA hand radiographs, and to quantify the JSW of these joints.
26010182 Antimalarial drugs alone may still have a role in rheumatoid arthritis. 2015 Jun OBJECTIVES: Antimalarials have been used for the treatment of rheumatoid arthritis (RA) for several decades. Current guidelines do not include the use of these drugs alone for RA patients. The purpose of the study is to review RA patients, to find those who have done well on antimalarials alone, and see if there are common features that predict good treatment outcome with these drugs. METHODS: This is a retrospective chart review of patients who have been successfully treated with antimalarials alone. Patients who were attending routine follow-up and were seemingly in remission defined by no swollen or tender joints were selected over a 6-month period. Those who had being doing well but were now or had been on other agents were not included. The background data were reviewed to see if there were any common initial characteristics. RESULTS: Thirty-three patients were seen who had been administered antimalarials alone and where initial data were available. Patients remain in clinical remission. Based on clinical observation, inflammatory markers, and radiographic reports, in the follow-up visits, they remain with no signs of inflammation and no new erosions on radiograph. Initial bone erosions on 2 patients remain stable over the years. CONCLUSIONS: There are some patients with confirmed RA who without doubt respond well to antimalarials alone. It is hard to objectively measure whether mild disease activity, early treatment initiation, lack of smoking, or other factors are contributing to a good treatment response.
26895106 Pathway of PPAR-gamma coactivators in thermogenesis: a pivotal traditional Chinese medicin 2016 Mar 29 Traditional Chinese medicine (TCM) syndromes have been regarded as the crucial clinical manifestations for individualized diagnosis and treatment of complex diseases, including rheumatoid arthritis (RA) and cancer. Especially, RA patients are classified into cold and hot syndromes with different clinical manifestations, interventions and molecular mechanisms. Better effectiveness of a classic cold syndrome-specific herbal formula Wu-tou decoction (WTD) has been achieved. To explore molecular mechanisms of syndrome-specific formulae is of great clinical significance to improve the effectiveness and pertinence of treatment for the complex diseases with personalized conditions. However, the scientific basis of WTD treatment on RA with the cold syndrome remains unclear. Here, we predicted the putative targets for composite compounds contained in WTD using drugCIPHER-CS and constructed a WTD herbs-putative targets-RA related genes network. Next, a list of major WTD targets was identified based on their topological features, including the degree, node betweenness, closeness and k-coreness in the above pharmacological network. Importantly, pathway enrichment analysis revealed that these major WTD targets were significantly associated with the pathway of peroxisome proliferator-activated receptor (PPAR)-gamma (PPAR-γ) coactivators in thermogenesis. These computational findings were subsequently verified by experiments on a rat model of collagen-induced arthritis (CIA) with cold or hot syndromes, and on human fibroblast-like synoviocytes-rheumatoid arthritis (HFLS-RA) cell line. In conclusion, the pathway of PPAR-γ coactivators in thermogenesis might be one of the potential pharmacological targets of WTD to alleviate RA with the TCM cold syndrome. These findings may open new avenues for designing individualized treatment regimens for RA patients.
27307417 Chronic pain experience on depression and physical disability: The importance of acceptanc 2019 Feb The mediating effect of acceptance and mindfulness in the relationship between pain, depression, and physical disability was examined in 55 rheumatoid arthritis patients. Results showed that the relationship between pain and depression was mediated by both nonreact and acceptance. By contrast, the relationship between pain and physical disability was mediated by acceptance but not by nonreact. This study provides evidences that the influence of these processes is different on depression and on physical disability. These findings support models that take both general measures of mindfulness and content-specific measures of acceptance into account when conceptualizing rheumatoid arthritis. Theoretical and clinical implications are discussed.
27906049 Smad-dependent mechanisms of inflammatory bone destruction. 2016 Dec 1 Homeostatic bone remodelling becomes disturbed in a variety of pathologic conditions that affect the skeleton, including inflammatory diseases. Rheumatoid arthritis is the prototype of an inflammatory arthritis characterised by chronic inflammation, progressive cartilage destruction and focal bone erosions and is a prime example for a disease with disturbed bone homeostasis. The inflammatory milieu favours the recruitment and activation of osteoclasts, which have been found to be the cells that are primarily responsible for bone erosions in many animal models of inflammatory arthritis. Among the inflammatory modulators, members of the transforming growth factor (TGF)-β super family are shown to be important regulators in osteoclastogenesis with Smad-mediated signalling being crucial for inducing osteoclast differentiation. These findings have opened a new field for exploring mechanisms of osteoclast differentiation under inflammatory conditions. Recent studies have shown that the TGF-β superfamily members TGF-β1, myostatin and activin A directly regulate osteoclast differentiation through mechanisms that depend on the RANKL-RANK interplay. These growth factors transduce their signals through type I and II receptor serine/threonine kinases, thereby activating the Smad pathway. In this review, we describe the impact of inflammation-induced Smad signalling in osteoclast development and subsequently bone erosion in rheumatoid arthritis.
27170517 Treatment of rheumatoid arthritis during pregnancy: present and future. 2016 Sep INTRODUCTION: For the management of rheumatoid arthritis patients who plan to become pregnant, both disease activity and therapeutic regimens have to be taken into consideration. In the case of stable inactive disease, pregnancy can be planned and therapy can be adjusted with drugs compatible with pregnancy. AREAS COVERED: Drugs to be discontinued before pregnancy are methotrexate, leflunomide, tocilizumab, rituximab, abatacept and tofacitinib. Pregnancy compatible disease modifying drugs are antimalarial drugs and sulfasalazine. TNF-inhibitors can be continued during the first half of pregnancy, yet if indicated during the third trimester TNF-inhibitors with a low rate of transplacental passage should be used. Glucocorticoids may be considered at the lowest effective dose throughout pregnancy. Non-selective COX-inhibitors can be continued until gestational week 32. Expert commentary: Together, a tailored treatment throughout pregnancy is possible with reasonable safety. Controlling disease activity during pregnancy is important for both, maternal and fetal health.
27497159 Anti cytokine therapy in chronic inflammatory arthritis. 2016 Oct This is a review looking at anti cytokine therapy in Rheumatoid Arthritis (RA), Psoriatic Arthritis (PSA) and Ankylosing Spondylitis (AS). The review explores the similarities and differences in the clinical features, as well as treatments and cytokines involved in the development and propagation of the disease. Particular attention is paid to TNFα inhibitors IL-1ra, IL-6 and JAK kinase Inhibitors, anti IL23 and IL-12 and the new developments with anti-IL-17.
27515048 Toll-like receptors: promising therapeutic targets for inflammatory diseases. 2016 Aug The health of living organisms is constantly challenged by bacterial and viral threats. The recognition of pathogenic microorganisms by diverse receptors triggers a variety of host defense mechanisms, leading to their eradication. Toll-like receptors (TLRs), which are type I transmembrane proteins, recognize specific signatures of the invading microbes and activate a cascade of downstream signals inducing the secretion of inflammatory cytokines, chemokines, and type I interferons. The TLR response not only counteracts the pathogens but also initiates and shapes the adaptive immune response. Under normal conditions, inflammation is downregulated after the removal of the pathogen and cellular debris. However, a dysfunctional TLR-mediated response maintains a chronic inflammatory state and leads to local and systemic deleterious effects in host cells and tissues. Such inappropriate TLR response has been attributed to the development and progression of multiple diseases such as cancer, autoimmune, and inflammatory diseases. In this review, we discuss the emerging role of TLRs in the pathogenesis of inflammatory diseases and how targeting of TLRs offers a promising therapeutic strategy for the prevention and treatment of various inflammatory diseases. Additionally, we highlight a number of TLR-targeting agents that are in the developmental stage or in clinical trials.
26152731 Recent progress and perspective in JAK inhibitors for rheumatoid arthritis: from bench to 2015 Sep Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by synovial inflammation and joint destruction. However, the combined use of synthetic disease-modifying anti-rheumatic drug (DMARD) such as methotrexate and a biological DMARD targeting tumour necrosis factor (TNF) has revolutionized treatment of RA. Clinical remission is a realistic target to treat and the maintenance of remission has produced significant improvements in structural and function outcomes. However, biological DMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed. The multiple cytokines and cell surface molecules bind to receptors, resulting in the activation of various signalling, including phosphorylation of kinase proteins. Among multiple kinases, Janus kinase (JAK) plays pivotal roles in the pathological processes of RA. Tofacitinib, a small product targeting JAK, inhibits phosphorylation of JAK1 and JAK3, subsequent Stat1 and expression of Stat1-inducible genes, which contribute to efficient propagation of its anti-inflammatory effects for the treatment of RA. The primary targets of tofacitinib are dendritic cells, CD4(+) T cells such as Th1 and Th17 and activated B cells which leads to multi-cytokine targeting. Six global phase 3 studies revealed that oral administration of 5 or 10 mg tofacitinib was significantly effective than placebo with or without methotrexate in active RA patients with methotrexate-naïve, inadequately responsive to methotrexate or TNF-inhibitors. Therapeutic efficacy of tofacitinib was observed in a short term after administration and was as strong as adalimumab, a TNF-inhibitor. The most commonly observed adverse events were related to infection, hematologic, hepatic and renal disorders and association of tofacitinib with carcinogenicity and infections remains debated. Further investigation on post-marketing survey would help us understand the positioning of this drug.
26214836 The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized a 2015 Aug We carried out metagenomic shotgun sequencing and a metagenome-wide association study (MGWAS) of fecal, dental and salivary samples from a cohort of individuals with rheumatoid arthritis (RA) and healthy controls. Concordance was observed between the gut and oral microbiomes, suggesting overlap in the abundance and function of species at different body sites. Dysbiosis was detected in the gut and oral microbiomes of RA patients, but it was partially resolved after RA treatment. Alterations in the gut, dental or saliva microbiome distinguished individuals with RA from healthy controls, were correlated with clinical measures and could be used to stratify individuals on the basis of their response to therapy. In particular, Haemophilus spp. were depleted in individuals with RA at all three sites and negatively correlated with levels of serum autoantibodies, whereas Lactobacillus salivarius was over-represented in individuals with RA at all three sites and was present in increased amounts in cases of very active RA. Functionally, the redox environment, transport and metabolism of iron, sulfur, zinc and arginine were altered in the microbiota of individuals with RA. Molecular mimicry of human antigens related to RA was also detectable. Our results establish specific alterations in the gut and oral microbiomes in individuals with RA and suggest potential ways of using microbiome composition for prognosis and diagnosis.
25903203 Breast lumps: a rare site for rheumatoid nodules. 2015 Apr 22 Granulomatous mastitis (GM) of the breast is a rare benign inflammatory disease and its presentation closely mimics breast cancer. Its diagnosis is mainly based on histology and there is no consensus agreement regarding its management. We report a case of a 60-year-old woman presenting with a right breast lump associated with a history of rheumatoid arthritis and raised rheumatoid factor. Following triple assessment (history and examination, imaging and biopsy), GM was diagnosed and she was treated conservatively.
26078482 Increased Serum Interleukin-9 Levels in Rheumatoid Arthritis and Systemic Lupus Erythemato 2015 The purpose of this paper was to evaluate the levels of IL-9 in patients with SLE and RA compared with controls and the association of IL-9 levels with clinical and laboratory parameters. IL-9 levels were assessed in 117 SLE patients, 67 RA patients, and 24 healthy controls by ELISA. Clinical and laboratory parameters were recorded. The IL-9 serum levels were significantly higher in RA patients (4,77 ± 3,618 pg/mL) and in SLE patients (12,26 ± 25,235 pg/mL) than in healthy individuals (1,22 ± 0,706 pg/mL) (p < 0,001). In SLE patients, there were no statistically significant associations or correlations between the levels of IL-9 and SLEDAI or other clinical and laboratorial parameters, with the exception of disease time, which showed a statistically significant negative correlation with IL-9 levels (r = -0,1948; p = 0,0378). In RA patients, no association or statistically significant correlation was observed with disease duration, DAS28, HAQ, rheumatoid factor positivity, or erosions on radiography. These data demonstrated increased serum levels of IL-9 in SLE and RA patients, but further studies are needed to clarify the precise role of this cytokine and its potential use as therapeutic target.
26121856 [Effect of Phellinus Polysaccharide on Canonical Wnt Signaling in Synovium in Rats with Rh 2015 May OBJECTIVE: To investigate the role of Phellinus Polysaccharide (FPS) in activating canonical Wnt signaling in rats with rheumatoid arthritis (RA). METHODS: Male SD rats were randomly divided into three groups (normal group, RA model group and PPS treated RA group), each with 10 rats. The RA model rats were prepared through intradermal injection of 0. 1 mL complete Freund's adjuvant into the right rear toes of the rats. The PPS treated RA rats were given 50 mg/kg PPS by gavage eight days after the introduction of RA. All rats were evaluated with arthritis score and paw swelling score at day 16, 20, 24, 28, 32. At day 28, the expressions of fibronectin gene, Wnt signal pathway negative regulation gene SFRP1,2 and Wnt key gene β-catenin, C-myc, and ccndl were detected by real time qPCR. RESULTS: PPS significantly reduced the arthritis score and paw swelling score of RA model rats. Lower levels of expression of SFRP1, 2 and higher levels of expression of β-catenin, C-myc, ccndl and fibronectin were found in the RA model rats compared with the normal controls. PPS increased the expression of SFRP1, 2 and decreased the expression of β-catenin, C-myc, ccndl and fibronectin in the RA rats. CONCLUSION: PPS has significant therapeutic effect on RA model rats through inhibiting canonical Wnt signaling.
27311188 [Tofacitinib for the treatment of rheumatoid arthritis]. 2016 Jun The combined use of synthetic disease-modifying anti-rheumatic drugs (sDMARDs) such as methotrexate and biological DMARDs (bDMARDs) has revolutionized treatment of rheumatoid arthritis (RA). Remission is now realistic targets, achieved by a large proportion of RA patients. However, bDMARDs are limited to intravenous or subcutaneous uses and orally available small but strong products have been developed. Oral administration of tofacitinib targeting the Janus kinase (JAK) is significantly effective than placebo in active RA patients with sDMARD-naïve, inadequately responsive to sDMARDs or TNF-inhibitors. The efficacy was rapid and as strong as adalimumab, a TNF-inhibitor. The common adverse events were related to infection, hematologic and hepatic disorders and association of tofacitinib with carcinogenicity and infections remains debated.
26725745 Influenza and pneumococcal vaccine coverage in 584 patients taking biological therapy for 2016 Mar OBJECTIVES: To evaluate influenza and pneumococcal vaccine coverage in patients taking biological therapy for chronic inflammatory joint disease and to identify factors associated with the decision to administer these two vaccines. METHODS: Retrospective cross-sectional questionnaire study of a cohort of 584 patients taking biological therapy for chronic inflammatory joint disease (rheumatoid arthritis or spondyloarthritis). We studied the influenza and pneumococcal vaccine coverage rates, information about these vaccines given to patients by the primary-care physician and rheumatologist, and reasons for not administering the vaccines. RESULTS: Overall vaccine coverage rates were 44% for influenza and 62% for pneumococcus. Factors associated with being vaccinated were patient age, previous influenza vaccination, and patient information. Concern about adverse effects and absence of patient information by the primary-care physician and rheumatologist were associated with very low coverage rates. CONCLUSION: This study showed insufficient vaccine coverage rates, particularly against influenza, in a population at high risk because of exposure to biological therapy. Patient information by healthcare professionals about influenza and pneumococcal vaccination has a major impact and should be renewed as often as possible.
26059944 Differences in the prevalence and characteristics of metabolic syndrome in rheumatoid arth 2015 Dec The purpose of the study was to examine whether rheumatoid arthritis (RA) patients have higher prevalence of metabolic syndrome (MetS) than osteoarthritis (OA) patients in association with a higher level of chronic systemic inflammation in rheumatoid arthritis. A total of 583 RA and 344 OA outpatients were analyzed in this multicentric study. Metabolic syndrome was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. A 1.6-fold higher prevalence of MetS was found in patients with OA compared with the RA patients. Among the parameters of MetS, patients with OA had significantly higher levels of waist circumference, systolic blood pressure, fasting blood glucose and triglycerides, whereas HDL cholesterol and diastolic blood pressure values were similar in both groups of patients. Higher values of inflammatory markers [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] in MetS than in non-MetS patients and higher prevalence of MetS in patients with CRP level ≥5 mg/L in both RA and OA patients were found. In multivariate logistic regression analysis, significant predictors of MetS were type of arthritis (OA vs. RA; OR 2.5 [95 % CI 1.82-3.43]), age (OR 1.04 [95 % CI 1.03-1.06]) and ESR (OR 1.01; [95 % CI 1.00-1.01]). The significant association between OA and MetS was maintained in the regression model that controlled for body mass index (OR 1.87 [95 % CI 1.34-2.61]). The present analysis suggests that OA is associated with an increased risk of MetS, which may be due to a common underlying pathogenic mechanism.
26450515 Serum Trace Element Concentrations in Rheumatoid Arthritis. 2016 Jun Rheumatoid arthritis (RA) is a condition that is associated with oxidative stress. Serum trace elements and their related transport proteins, e.g., albumin and ceruloplasmin, play an important role in the antioxidant defense. Trace element status may therefore be involved in the pathogenesis of RA or be affected by the disease activity of this chronic inflammatory condition. The study participants were 110 patients with RA and 100 sex- and age-matched healthy volunteers. Serum concentrations of albumin, ceruloplasmin, selenium, zinc, copper, and zinc/copper ratio were measured in all subjects. The relationship between these parameters and disease activity score was also assessed. Lower concentrations of serum Alb, Zn, and Se were independently related to disease activity index. High concentrations of serum copper were associated with the presence of RA. Serum Cu concentrations were positively related to disease activity as assessed by the disease activity score. Low serum concentrations of Zn and Se, and high serum Cu concentrations may be associated with the presence of RA or be a consequence of this condition. Of the trace elements that were investigated in the present study, only serum Cu was positively correlated with disease activity.
25630616 Is the microRNA-146a (rs2910164) polymorphism associated with rheumatoid arthritis? Associ 2015 May BACKGROUND: To investigate a possible effect of a gene mutation on rheumatoid arthritis (RA), we performed genotyping, in a hospital-based, case-control study in a Chinese cohort, relating the single nucleotide polymorphism (SNP) of microRNA (miRNA)-146a (rs2910164) to RA and undertook a meta-analysis using the available literature. METHODS: Six hundred and fifteen RA patients and 839 controls were enrolled in our study. A polymorphism of the miRNA-146a (rs2910164) gene was detected using a custom-by-design 48-Plex SNPscan TM Kit. In addition, we performed a systematic literature research and identified an additional 7 studies with 1066 cases and 1513 controls. RESULTS: We did not find a significant association of miRNA-146a polymorphism with an RA risk in our data. And the results of the meta-analyses suggested no significant association between miRNA-146a polymorphism and RA in any genetic model. However, when the subgroup analyses were performed, genotype GG was observed to be significantly associated with RA in females. And the DAS28 score may also be significantly influenced by CC genotype. CONCLUSIONS: Our study suggested that miRNA-146a polymorphism might not be associated with RA susceptibility. However, the miRNA-146 GG genotype might increase the risk of RA in females, and CC genotype may influence disease activity when evaluated with DAS28 score.
27866179 Tripterygium Glycosides for Treating Late-onset Rheumatoid Arthritis: A Systematic Review 2016 Nov Context • Older- or late-onset rheumatoid arthritis (LORA) is defined as rheumatoid arthritis (RA) with an onset of symptoms at age 60 y or older, which includes a specific clinical course and features. To date, a specific therapeutic treatment for LORA is still a dilemma in modern medicine. Objective • The study aimed to assess the effectiveness and safety of Tripterygium glycosides for treating LORA. Design • Seven databases were searched from their inceptions until June 2015. The research team included randomized, controlled trials (RCTs) in which Tripterygium glycosides were employed, either alone or as an adjuvant treatment with disease-modifying antirheumatic drugs (DMARDs), in patients with LORA. The selection of studies, data extraction, and validation were performed independently by 2 reviewers. The Cochrane risk-of-bias criteria were used for evaluating the quality of the included studies. Settings • The study was conducted at Changzhou University (Changzhou, China), Nanjing University of Chinese Medicine (Nanjing, China), and the hospital affiliated with Nanjing University of Chinese Medicine (Nanjing, China). Participants • Studies including patients aged 60 y or older with RA in any of their peripheral joints were included in the meta-analysis. Intervention • All participants in the included studies were administered Tripterygium glycosides, either alone or together with other DMARDs, for at least 3 mo. Outcome Measures • The primary outcomes included (1) the swollen joint count (SJC) and (2) the tender joint count (TJC). The secondary outcomes included the erythrocyte sedimentation rate (ESR) and the level of C-reactive protein (CRP). Results • Four RCTs met the inclusion criteria, and most of them were of low methodological quality. The results of the current meta-analysis indicated that Tripterygium glycosides plus DMARD therapy, when compared with DMARD therapy alone, showed a favorable effect: (1) on the SJC, with the mean difference (MD) = -1.58, 95% confidence interval (CI) = -1.64 to -1.51, and P < .01; (2) on the TJC, with the MD = -1.71, 95% CI = -2.26 to -1.15, and P < .01; (3) on the CRP levels, with the MD = -9.96, 95% CI = -10.96 to -8.96, and P < .01; and (4) on the ESR, with MD = -10.74, 95% CI = -12.47 to -9.00, and P < .01. In addition, the groups treated with Tripterygium glycosides were not superior to the intervention groups that did not use Tripterygium glycosides in terms of decreasing adverse events. Conclusions • A lack of sufficient trials contributed to the small sample size of the combined, eligible RCTs, and it was difficult to draw firm conclusions on the positive effects of Tripterygium glycosides and on their efficacy as an effective intervention for treating RA. A high risk of bias existed among the available RCTs. Further work with more RCTs on a larger patient population is necessary to confirm the efficacy and safety of Tripterygium glycosides for treating LORA.
27330157 A disintegrin and metalloprotease-17 and galectin-9 are important regulators of local 4-1B 2016 Oct OBJECTIVE: Co-stimulatory T cell cytokines are important in the progression of RA. This study investigates the interplay between 4-1BB, a disintegrin and metalloprotease-17 (ADAM17) and galectin-9 (Gal-9) in RA. METHODS: Stimulated mononuclear cells from patients with chronic RA (n = 12) were co-incubated with tissue inhibitor of metalloproteinase, 4-1BB ligand and Gal-9. Plasma samples were examined for soluble 4-1BB (s4-1BB) in newly diagnosed, treatment-naïve patients with RA (n = 97). The 28-joint DAS with CRP (28DAS-CRP), total Sharp score, erosion score and joint space narrowing were used to evaluate treatment outcome serially over a 2-year period. RESULTS: RA CD4(+) and CD8(+) synovial T cells express high levels of 4-1BB. The addition of TNF-α to cultured synovial mononuclear cells increased shedding of 4-1BB. 4-1BB ligand only increased TNF-α shedding in combination with Gal-9. RNA interference-mediated knockdown of ADAM17 or the addition of an ADAM17 inhibitor reduced the 4-1BB shedding. Shedding of 4-1BB was not influenced by Gal-9. Plasma levels of s4-1BB were increased in early RA and correlated with the number of swollen joints at baseline. After 3 months of treatment, the plasma levels of s4-1BB were equal to those of the controls. Baseline plasma levels of s4-1BB were inversely correlated with DAS28-CRP after 2 years of treatment, but not with total Sharp score, erosion score or joint space narrowing. CONCLUSION: ADAM17 induces 4-1BB shedding in RA. Gal-9 is pivotal for the function of 4-1BB and induction of TNF-α. Furthermore, high plasma levels of s4-1BB were associated with the number of swollen joints, but also with a low DAS28-CRP after 2 years treatment in early RA.