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ID PMID Title PublicationDate abstract
25019600 Cost-effectiveness of a one-year coaching program for healthy physical activity in early r 2015 PURPOSE: To describe cost-effectiveness of the Physical Activity in Rheumatoid Arthritis (PARA) study intervention. METHOD: Costs were collected and estimated retrospectively. Cost-effectiveness was calculated based on the intervention cost per patient with respect to change in health status (EuroQol global visual analog scale--EQ-VAS and EuroQol--EQ-5D) and activity limitation (Health assessment questionnaire - HAQ) using cost-effectiveness- and cost-minimization analyses. RESULTS: Total cost of the one-year intervention program was estimated to be €67 317 or €716 per participant. Estimated difference in total societal cost between the intervention (IG) and control (CG) was €580 per participant. Incremental cost-effectiveness ratio (ICER) for one point (1/100) of improvement in EQ-VAS was estimated to be €116. By offering the intervention to more affected participants in the IG compared to less affected participants, 15.5 extra points of improvement in EQ-VAS and 0.13 points of improvement on HAQ were gained at the same cost. "Ordinary physiotherapy" was most cost-effective with regard to EQ-5D. CONCLUSIONS: The intervention resulted in improved effect in health status for the IG with a cost of €116 per extra point in VAS. The intervention was cost-effective if targeted towards a subgroup of more affected patients when evaluating the effect using VAS and HAQ. IMPLICATIONS FOR REHABILITATION: The physical activity coaching intervention resulted in an improved effect on VAS for the intervention group, to a higher cost. In order to maximize cost-effectiveness, this type of physical activity coaching intervention should be targeted towards patients largely affected by their RA. The intervention is cost-effective from the patients' point of view, but not from that of the general population.
23932722 Risk of herpes/herpes zoster during anti-tumor necrosis factor therapy in patients with rh 2014 May BACKGROUND: TNF blockers have demonstrated efficacy in inflammatory rheumatic diseases (IRDs). The drugs are associated with a moderate but definite risk of bacterial infection, but risk of viral infection is not clearly known. OBJECTIVE: To assess the risk of herpes zoster (HZ) reactivation in patients with rheumatoid arthritis (RA) receiving TNF blockers as compared with DMARDs. METHODS: A systematic search of literature up to March 2013 was performed, in MEDLINE, EMBASE, the Cochrane library and abstracts from the ACR and EULAR congresses from 2008 to 2011. Studies were included if they reported the incidence of HZ, respectively, in patients receiving anti-TNF and conventional DMARDs. RESULTS: The literature search identified 3446 articles and 88 congress abstracts; a manual search retrieved seven articles. Finally, 26 articles and nine abstracts were included; six articles and one abstract were of meta-analyses estimating the relative risk of HZ in patients with RA with a total follow-up of 163,077 patient-years. From the meta-analyses of data for seven registries, the pooled risk ratio for HZ with TNF blockers was 1.61 [95% CI 1.16-2.23] (P = 0.004). Proportions of severe HZ ranged from 4.9% to 20.9% with TNF-blockers and from 2.0% to 5.5% with conventional DMARDs, in the different registries. CONCLUSIONS: This meta-analysis revealed a significantly increased risk of HZ, up to 61%, in patients with IRD receiving TNF blockers. These data raise the issue of systematic prophylactic treatment with known history of HZ or vaccination without this history.
23933508 GM-CSF as a therapeutic target in inflammatory diseases. 2013 Dec GM-CSF is a well-known haemopoietic growth factor that is used in the clinic to correct neutropaenia, usually as a result of chemotherapy. GM-CSF also has many pro-inflammatory functions and recent data implicates GM-CSF as a key factor in Th17 driven autoimmune inflammatory conditions. In this review we summarize the findings that have led to the development of GM-CSF antagonists for the treatment of autoimmune diseases like rheumatoid arthritis (RA) and discuss some results of recent clinical trials of these agents.
25178741 Contribution of ethnic group and socioeconomic status to degree of disability in rheumatoi 2015 Apr The aim of this study was to estimate the contributions of ethnic group and socioeconomic status as social determinants related to disability and disease activity in Chilean Mapuche and non-Mapuche patients with rheumatoid arthritis (RA). Descriptive cross-sectional study with a stratified hospital-based sample of 189 patients in treatment with disease-modifying anti-rheumatic drugs. We assessed disability as categorical variable with the Health Assessment Questionnaire, disease activity with the Disease Activity Score instrument, and socioeconomic status with a standard questionnaire used by the Chilean government. Measures of association, stratified analyses and a multiple logistic regression model were used to analyze the data using the Stata 12.1 software package. Low socioeconomic status (annual income below US$ 7,200) is associated with disability (OR 3.87 CI 1.68-9.20) and Mapuche ethnic identity also contributes to disability (OR 2.48, CI 1.09-5.89). Relevant but not statistically significant in multivariable models were variables such as age, gender and place of residence. RA patients with a low socioeconomic status have almost three times the odds of having a moderate to high disability, independent of their ethnic group, gender or place of residence. Therefore, healthcare efforts should be aimed at promoting early diagnosis and prompt treatment among populations with high levels of poverty, which in the region of the Araucanía means primarily indigenous rural areas.
25099015 Molecular imaging of rheumatoid arthritis: emerging markers, tools, and techniques. 2014 Apr 15 Early diagnosis and effective monitoring of rheumatoid arthritis (RA) are important for a positive outcome. Instant treatment often results in faster reduction of inflammation and, as a consequence, less structural damage. Anatomical imaging techniques have been in use for a long time, facilitating diagnosis and monitoring of RA. However, mere imaging of anatomical structures provides little information on the processes preceding changes in synovial tissue, cartilage, and bone. Molecular imaging might facilitate more effective diagnosis and monitoring in addition to providing new information on the disease pathogenesis. A limiting factor in the development of new molecular imaging techniques is the availability of suitable probes. Here, we review which cells and molecules can be targeted in the RA joint and discuss the advances that have been made in imaging of arthritis with a focus on such molecular targets as folate receptor, F4/80, macrophage mannose receptor, E-selectin, intercellular adhesion molecule-1, phosphatidylserine, and matrix metalloproteinases. In addition, we discuss a new tool that is being introduced in the field, namely the use of nanobodies as tracers. Finally, we describe additional molecules displaying specific features in joint inflammation and propose these as potential new molecular imaging targets, more specifically receptor activator of nuclear factor κB and its ligand, chemokine receptors, vascular cell adhesion molecule-1, αVβ₃ integrin, P2X7 receptor, suppression of tumorigenicity 2, dendritic cell-specific transmembrane protein, and osteoclast-stimulatory transmembrane protein.
24368568 Solomonsterol A, a marine pregnane-X-receptor agonist, attenuates inflammation and immune 2013 Dec 24 In the present study we provide evidence that solomonsterol A, a selective pregnane X receptor (PXR) agonist isolated from the marine sponge Theonella swinhoei, exerts anti-inflammatory activity and attenuates systemic inflammation and immune dysfunction in a mouse model of rheumatoid arthritis. Solomonsterol A was effective in protecting against the development of arthritis induced by injecting transgenic mice harboring a humanized PXR, with anti-collagen antibodies (CAIA) with beneficial effects on joint histopathology and local inflammatory response reducing the expression of inflammatory markers (TNFα, IFNγ and IL-17 and chemokines MIP1α and RANTES) in draining lymph nodes. Solomonsterol A rescued mice from systemic inflammation were assessed by measuring arthritis score, CRP and cytokines in the blood. In summary, the present study provides a molecular basis for the regulation of systemic local and systemic immunity by PXR agonists.
23703660 The -319C/+49G/CT60G haplotype of CTLA-4 gene confers susceptibility to rheumatoid arthrit 2013 Several single nucleotide polymorphisms (SNPs) within the CTLA-4 gene and elevated serum levels of soluble CTLA-4 (sCTLA-4) have been associated with autoimmunity including rheumatoid arthritis (RA). In this case-control study, we evaluated the relationship between the -319C/T (rs5742909) and CT60 G/A (rs3087243) SNPs and sCTLA-4 levels in 200 RA patients and 200 control subjects (CS) from Western Mexico. Both SNPs were genotyped with the polymerase chain reaction-restriction fragment length polymorphism technique and the sCTLA-4 levels were quantified using an enzyme-linked immunosorbent assay kit. In addition, we performed a haplotype analysis, including our previous data of the +49A/G (rs231775) SNP. The G/A genotype of the rs3087243 SNP was associated with a decreased risk of RA [odd ratio (OR) 0.61, 95% confidence interval (CI) 0.38-0.96, p = 0.024]. This protection was also observed in the negative anti-cyclic citrullinated peptide group of RA carriers of the A allele (OR 0.48, 95% CI 0.22-1.05, p = 0.042). On the contrary, we identified the -319C/+49G/CT60G haplotype of CTLA-4 gene as a risk factor for RA (OR 1.69, 95% CI 1.13-2.52, p = 0.01). The sCTLA-4 levels were not associated with RA (p = 0.377), but were correlated with the functional disability of these patients (r = 0.282, p = 0.012). However, in CS the C/T genotype of the rs5742909 SNP, as well as the G/G and G/A genotypes of the rs3087243 SNP were associated with higher sCTLA-4 levels (p < 0.001). In conclusion, our results suggest that the -319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease. Moreover, both SNPs showed an effect on the sCTLA-4 production in our control population. However, further studies are required to evaluate the role of sCTLA-4 in RA, as well as the molecular and functional basis of the association between both CTLA-4 gene SNPs and soluble levels of CTLA-4 in CS.
24269820 CTRP3 plays an important role in the development of collagen-induced arthritis in mice. 2014 Jan 3 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease exhibited most commonly in joints. We found that the expression of C1qtnf3, which encodes C1q/TNF-related protein 3 (CTRP3), was highly increased in two mouse RA models with different etiology. To elucidate the pathogenic roles of CTRP3 in the development of arthritis, we generated C1qtnf3(-/-) mice and examined the development of collagen-induced arthritis in these mice. We found that the incidence and severity score was higher in C1qtnf3(-/-) mice compared with wild-type (WT) mice. Histopathology of the joints was also more severe in C1qtnf3(-/-) mice. The levels of antibodies against type II collagen and pro-inflammatory cytokine mRNAs in C1qtnf3(-/-) mice were higher than WT mice. These observations indicate that CTRP3 plays an important role in the development of autoimmune arthritis, suggesting CTRP3 as a possible medicine to treat RA.
25443993 Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy C 2015 Feb Eosinophilic myositis is characterized by eosinophilic infiltration of skeletal muscles. In the absence of an identifiable causative factor or source (including parasitic infection, intake of drugs or L-tryptophan, certain systemic disorders as well as malignant diseases), the diagnosis of idiopathic eosinophilic myositis is usually retained. However, some muscular dystrophies have been recently identified in this subset of eosinophilic myositis. Here, we report a patient with an 8 kb CCTG expansion in intron 1 of the CNBP gene, a mutation characteristic of myotonic dystrophy type 2 (DM2), whose first manifestation was "idiopathic" eosinophilic myositis. This report suggests that in "idiopathic" eosinophilic myositis, clinicians should consider muscular dystrophies, including DM2.
23594471 Introduction to statistical modelling: linear regression. 2015 Jul In many studies we wish to assess how a range of variables are associated with a particular outcome and also determine the strength of such relationships so that we can begin to understand how these factors relate to each other at a population level. Ultimately, we may also be interested in predicting the outcome from a series of predictive factors available at, say, a routine clinic visit. In a recent article in Rheumatology, Desai et al. did precisely that when they studied the prediction of hip and spine BMD from hand BMD and various demographic, lifestyle, disease and therapy variables in patients with RA. This article aims to introduce the statistical methodology that can be used in such a situation and explain the meaning of some of the terms employed. It will also outline some common pitfalls encountered when performing such analyses.
23439407 Dual effects of IL-1 overactivity on the immune system in a mouse model of arthritis due t 2013 Feb 20 Previous studies have revealed the significance of cytokine interleukin 1 (IL-1) in the onset and progression of rheumatoid arthritis (RA). The precise molecular mechanisms related to IL-1 underlying RA is still elusive. We conducted a whole genome-wide transcriptomal comparison of wild-type (WT) and arthritis-prone IL-1 receptor antagonist (IL-1rn) deficient BALB/c mice to address this issue. To refine our search efforts, gene expression profiling was also performed on paired wild-type and arthritis-resistant IL-1rn deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes. Two hundred and fifteen transcripts were found to be dysregulated greater than or equal to 2-fold in the diseased mice. The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality, suggesting dual regulatory effects of IL-1 hyperactivity on immunological changes associated with arthritis development. Phase-specific gene expression changes were identified, such as early increase and late decrease of heat shock protein coding genes. Moreover, common gene expression changes were also observed, especially the upregulation of paired Ig-like receptor A (Pira) in both early and late phases of arthritis. Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex (MHC) class I inhibitor (brefeldin A) was carried out to investigate the role of suppressing Pira activity. We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.
23558520 Radio-lunate arthrodesis in rheumatoid arthritis: outcome and techniques. 2013 May BACKGROUND AND PURPOSE: The wrist is one of the most affected joints in rheumatoid arthritis. The purpose of this retrospective study was to assess clinical, functional and radiographic results of radio-lunate arthrodesis. Two different operation and fixation techniques are compared and detailed outcome after this intervention is presented. METHODS: Twenty-seven patients with long-standing rheumatoid arthritis were operated on, either by stabilisation of the arthrodesis with Shapiro staples (n = 14) or by Herbert screw (n = 13) and followed for a mean of 5.4 years. RESULTS: Radio-lunate arthrodesis resulted in high overall and subjective satisfaction concerning function, grip and return to work. Grip strength was 35 kPa for the dominant and 26 kPa for the non-dominant hand. No revision, pseudoarthrosis or hardware failure was observed; only two conservatively treated wound healing problems were reported. The procedure resulted in a mean flexion of 26° and a mean extension of 24°; a clear improvement was also seen in activities of daily life. No difference between both groups was observed for pain, complication rate or functional outcome. INTERPRETATION: Due to high patient satisfaction and functional outcome, radio-lunate wrist arthrodesis can be recommended independent of fixation method.
24578030 Rheumatoid arthritis during pregnancy and postnatal catch-up growth in the offspring. 2014 Jul OBJECTIVE: Active rheumatoid arthritis (RA) during pregnancy and the presence of rheumatoid factor (RF) or anti-citrullinated protein antibodies (ACPAs) are associated with lower birth weight of the child. Moreover, treatment of the mothers with prednisone may shorten the gestational age at birth. Rapid catch-up in weight for length during the first year of life has been related to a worse cardiovascular and metabolic profile in early adulthood. This study was therefore undertaken to assess the influence of RA disease activity, medication use, and presence of RF or ACPAs during pregnancy on the growth of the child in the first year of life. METHODS: Among 180 children born to mothers with RA, the tempo of catch-up in weight during the first year of life was studied. Independent variables were the extent of RA disease activity (according to the Disease Activity Score in 28 joints [DAS28]), medication use, and presence of RF or ACPAs during pregnancy. RESULTS: Of 167 children with available data, 52 (31%) showed catch-up in weight in the first year of life, of whom 90% (47 of 52) showed rapid catch-up. An elevated DAS28 score in the mother was associated with rapid catch-up in weight of the offspring, independent of maternal medication use or the presence of RF or ACPAs during pregnancy (odds ratio 1.44 [95% confidence interval 1.07-1.95] per 1-point increase in the DAS28). Use of medications during pregnancy had no influence on postnatal growth. CONCLUSION: Elevated RA disease activity during pregnancy should be avoided because it is associated with rapid postnatal catch-up in weight, a risk factor for a worse cardiovascular and metabolic profile in adults. Medication for RA during pregnancy, including prednisone, had no effect on growth. Continuation or extension of medication will not only improve maternal health during pregnancy, but could be beneficial for the future health of the unborn child.
25571192 Measurement of rehabilitation in thumb MP joint subluxation due to rheumatoid arthritis. 2014 As treatment for subluxation due to rheumatoid arthritis (RA), rehabilitation by hand therapy is one option, but the number of therapist is not sufficient. Therefore, a device for rehabilitation of thumb metacarpophalangeal (MP) joint subluxation has been developed. To improve the device, it is necessary to measure in close proximity to the actual rehabilitation. Therefore, the authors tried to measure two kinds of rehabilitation by using motion capture and a contact force sensor. To measure rehabilitation movements, three markers were attached to the metacarpal bone, six markers were attached to each side of the interphalangeal (IP) joint, MP joint and proximal phalanx of the right thumb of the subjects, and a finger model was created by these markers. Further, three markers were placed on the left index of the therapist, and force direction was calculated by these markers. Measurement was conducted on healthy subjects, Rehabilitation was performed by the person who is not a therapist, but received the guidance of the doctor who is coauthor. As a result, the authors could measure rehabilitation by hand therapy, force, point of action and displacement. The results suggest that rehabilitation with traction twice as efficient as that without traction. Furthermore, it was found that rehabilitation is possible with calculated force, and the force is reproducible by the actuator in the device.
24883333 Anti-hnRNP B1 (RA33) autoantibodies are associated with the clinical phenotype in Russian 2014 Heterogeneous nuclear ribonucleoproteins (hnRNPs) are potent autoantigenic targets in systemic autoimmune rheumatic diseases (SARD). Loss of tolerance to the RA33 complex consisting of hnRNP A2 and its alternatively spliced variants B1 and B2 has been the interest of rheumatologists. A novel ELISA for the detection of anti-hnRNP B1 autoantibodies has been developed to investigate the prevalence thereof in 397 patients with SARD, including patients with rheumatoid arthritis (RA), spondyloarthropathy (SPA), juvenile chronic arthritis, systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren's syndrome (SS), in comparison to 174 controls. Anti-hnRNP B1 autoantibodies were significantly more prevalent in patients with SARD than controls (47/397, 11.8% versus 2/174, 1.1%; P<0.001). In particular, anti-hnRNP B1 were found more frequently in the disease cohorts than in the controls and were present in 24/165 (14.5%) patients with RA, 6/58 (10.3%) SPA, 11/65 (16.9%) SSc, and 4/50 (8.0%) SLE. In RA patients, anti-hnRNP B1 autoantibodies correlated significantly with C-reactive protein levels and erythrocyte sedimentation rate, while in patients with SSc it was associated with features of arterial wall stiffness and presence of hypertension. Anti-hnRNP B1 autoantibodies occur in SARD and seem to be correlated with distinct clinical characteristics in patients with RA and SSc.
24986852 Longterm blood pressure variability in patients with rheumatoid arthritis and its effect o 2014 Aug OBJECTIVE: To examine longterm visit-to-visit blood pressure (BP) variability in patients with rheumatoid arthritis (RA) versus non-RA subjects and to assess its effect on cardiovascular (CV) events and mortality in RA. METHODS: Clinic BP measures were collected in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria met between January 1, 1995, and January 1, 2008) and non-RA subjects. BP variability was defined as within-subject SD in systolic and diastolic BP. RESULTS: The study included 442 patients with RA (mean age 55.5 yrs, 70% females) and 424 non-RA subjects (mean age 55.7 yrs, 69% females). Patients with RA had higher visit-to-visit variability in systolic BP (13.8 ± 4.7 mm Hg) than did non-RA subjects (13.0 ± 5.2 mm Hg, p = 0.004). Systolic BP variability declined after the index date in RA (p < 0.001) but not in the non-RA cohort (p = 0.73), adjusting for age, sex, and calendar year of RA. During the mean followup of 7.1 years, 33 CV events and 57 deaths occurred in the RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of CV events (HR per 1 mm Hg increase in BP variability 1.12, 95% CI 1.01-1.25). Diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95% CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, and use of antihypertensives. CONCLUSION: Patients with RA had higher visit-to-visit systolic BP variability than did non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse CV outcomes and all-cause mortality in RA.
23532440 Janus kinase inhibitors in autoimmune diseases. 2013 Apr Biological therapies directed at proinflammatory cytokines have irrevocably changed the landscape of treatment of rheumatoid arthritis (RA) and other autoimmune diseases. With the advances in our knowledge in cytokine signalling, the question emerges whether targeting intracellular signalling might also be a safe and efficacious strategy. Janus kinases or Jaks are critical for a large family of cytokines and the first Jak inhibitors has been approved by the FDA. It is therefore timely to consider this new category of drugs and reflect on their potential roles, present and future, in the treatment of RA and related disorders.
25649726 The design of a low literacy decision aid about rheumatoid arthritis medications developed 2014 Nov 25 BACKGROUND: Shared decision-making in rheumatoid arthritis (RA) care is a priority among policy makers, clinicians and patients both nationally and internationally. Demands on patients to have basic knowledge of RA, treatment options, and details of risk and benefit when making medication decisions with clinicians can be overwhelming, especially for those with limited literacy or limited English language proficiency. The objective of this study is to describe the development of a medication choice decision aid for patients with rheumatoid arthritis (RA) in three languages using low literacy principles. METHODS: Based on the development of a diabetes decision aid, the RA decision aid (RA Choice) was developed through a collaborative process involving patients, clinicians, designers, decision-aid and health literacy experts. A combination of evidence synthesis and direct observation of clinician-patient interactions generated content and guided an iterative process of prototype development. RESULTS: Three iterations of RA Choice were developed and field-tested before completion. The final tool organized data using icons and plain language for 12 RA medications across 5 issues: frequency of administration, time to onset, cost, side effects, and special considerations. The tool successfully created a conversation between clinician and patient, and garnered high acceptability from clinicians. CONCLUSIONS: The process of collaboratively developing an RA decision aid designed to promote shared decision making resulted in a graphically-enhanced, low literacy tool. The use of RA Choice in the clinical encounter has the potential to enhance communication for RA patients, including those with limited health literacy and limited English language proficiency.
24491906 [Mechanisms of osteoporosis development in patients with rheumatoid arthritis]. 2014 Feb 4 Rheumatoid arthritis (RA) is progressive, chronic, autoimmune, systemic connective tissue disease. It affects 0,5-1% population. RA manifests as inflammation of symmetrical mainly small and medium joints with synovial hypertrophy, extra-articular lesions and systemic complications. Depending on intensity and duration of RA in imaging studies the patients demonstrate narrowing of articular fissures, presence of geodes, erosions, subluxations and/or synostoses. Progressive bone mass loss in the joint involved by the morbid process and in the entire skeleton was also described. Local (periarticular) osteoporosis is linked to the presence of cytokines and growth factors, which regulate reciprocal interactions between osteoclasts, osteoblasts and immune system cells. In the inflamed joint accumulate synoviocytes of fibroblast phenotype, synoviocytes of macrophage phenotype, antigen presenting cells, lymphocytes T, activated lymphocytes B, plasma cells and neutrophils. Increased expression of receptor activator of nuclear factor κB (RANKL), macrophage-colony stimulating factor (M-CSF), presence of TNFα, IL-1, IL-6, IL-7, IL-17 influences pathological loss of bone mass. Rheumatoid arthritis is an important risk factor of generalised osteoporosis and fractures, involved in FRAX (fracture risk assessment) algorythm. Generalised osteoporosis in patients with RA has a multifactorial aetiology. Its development reflects effects of both: factors linked to the disease (presence of proinflammatory cytokines, disability of the patients, applied therapy) and classical risk factors of osteoporosis (e.g. advanced age, sex, post-menopausal period, genetic predisposition, low peak bone mass, low body weight, deficiency of calcium and vitamin D, tobacco smoking).
25022966 Interleukin-35 gene therapy exacerbates experimental rheumatoid arthritis in mice. 2014 Sep Interleukin (IL)-35 was initially described as an immunosuppressive cytokine specifically produced by CD4(+)FoxP3(+) regulatory T cells (Treg). Since Treg play a major role in autoimmunity control and protect from inflammation, we aimed at evaluating the role of IL-35 in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), using a non-viral gene transfer strategy. The clinical and histological effect of IL-35 was assessed in mice with CIA receiving an injection of two distinct plasmids encoding IL-35 gene (pIGneo-mIL-35 or pORF-mIL-35) 3 and 18 days after CIA induction. Treg and Th17 were characterized by flow cytometry in the spleen and lymph nodes of treated mice. Our results showed that whatever the plasmid used, IL-35 gene transfer resulted in a statistically significant increase in clinical scores of CIA compared to results with empty plasmid. The underlying cellular mechanisms of this effect were shown to be related to an increased Th17/Treg ratio in the spleen of pORF-mIL-35 treated mice. In conclusion, we show an unexpected but clear exacerbating effect of IL-35 gene transfer in an autoimmune and inflammatory RA model, associated with a modification of the Th17/Treg balance. Altogether, these result shows that this cytokine can promote chronic inflammation.