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ID PMID Title PublicationDate abstract
27484684 Vitamin D Deficiency and Rheumatoid Arthritis. 2017 Jun Vitamin D (VitD) is a hormone primarily synthesized in human skin under the stimulation of ultraviolet radiation. Beyond its endocrine role in bone metabolism, VitD is endowed with remarkable immunomodulatory properties. The effects of VitD on the immune system include the enhancement of microbicidal ability of monocytes/macrophages and the down-modulation of inflammatory cytokines produced by T lymphocytes. VitD deficiency is involved in many health problems, including immune-mediated diseases such as autoimmune disorders. Rheumatoid arthritis (RA) is a chronic inflammatory systemic autoimmune disease that compromises the joints, causing cartilage destruction and bone erosion. RA treatment usually consists of combined therapies that generally suppress the entire immune response leading to increased susceptibility to infections. This review describes the main effects of VitD on innate and adaptive immune system and also VitD status in inflammatory rheumatic diseases such as RA. Despite some controversies, the majority of reports reinforce the idea that lower VitD levels correlate with more severe clinical manifestations in RA and other rheumatic diseases. Therefore, supplementation with VitD to achieve normal serum levels is worthwhile as an aforethought. Original data concerning the potential applicability of 1,25-dihydroxyvitamin D(3) (VitD3), the active form of vitamin D, as a tolerogenic adjuvant are also included. In this sense, the effect of VitD3 associated with proteoglycan (PG), which is a specific cartilage antigen, was tested in the course of experimental arthritis. This association significantly lowered clinical scores and local histopathological alterations. Even though local analysis of T cell subsets and cytokine production did not reveal any difference between the experimental groups, VitD3+PG association significantly reduced cytokine production by spleen cells. These results suggest that VitD3 played a role as a tolerogenic adjuvant by down-modulating the course of experimental RA. Considering this tolerogenic effect of VitD3+PG association, further investigations will reveal its plausible use in human RA.
28607508 Systematic review and meta-analysis: pharmacogenetics of anti-TNF treatment response in rh 2017 Oct Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects ~1% of the Caucasian population. Over the last decades, the availability of biological drugs targeting the proinflammatory cytokine tumour necrosis factor α, anti-TNF drugs, has improved the treatment of patients with RA. However, one-third of the patients do not respond to the treatment. We wanted to evaluate the status of pharmacogenomics of anti-TNF treatment. We performed a PubMed literature search and all studies reporting original data on associations between genetic variants and anti-TNF treatment response in RA patients were included and results evaluated by meta-analysis. In total, 25 single nucleotide polymorphisms were found to be associated with anti-TNF treatment response in RA (19 from genome-wide association studies and 6 from the meta-analyses), and these map to genes involved in T cell function, NFκB and TNF signalling pathways (including CTCN5, TEC, PTPRC, FCGR2A, NFKBIB, FCGR2A, IRAK3). Explorative prediction analyses found that biomarkers for clinical treatment selection are not yet available.
29118439 Preventing progression from arthralgia to arthritis: targeting the right patients. 2018 Jan Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.
29276053 Inter-observer agreement of standard joint count examination and disease global assessment 2019 Sep OBJECTIVES: To assess the inter-observer agreement of standard joint count between experienced Rheumatology professor (Prof) and young Rheumatology fellow (candidate), and to compare disease global assessment between professor, young candidate and patients. METHODS: This study included one hundred rheumatoid arthritis patients. For all patients independent clinical evaluation was done by two rheumatologists (professor and candidate) for detection of tenderness in 28 joints and swelling in 26 joints. The study also involved global assessment of disease activity by the provider (Prof and candidate) (EGA) as well as by the patient (PGA). The EGA was determined without previous knowledge of the patient's laboratory test results. RESULTS: A highly significant accordance (correlation) between professor and candidate was found in both the number of tender joints (p<0.001) (r=0.946), and the number of swollen joints (p<0.001) (r=0.797). Regarding swollen joints, the highest agreement was in right knee (0.929), while poor agreement was found in the right 5th MCP (0.049). Regarding tender joints, the highest analogy was in the right elbow (0.899), in contrast to the left 3rd PIP (0.462) which showed the least congruence. Agreement study using kappa measurement for disease global assessment showed: moderate agreement (between professor and candidate) (0.405), fair agreement between (professor and patient) (0.213), fair agreement between (candidate and patient) (0.367). CONCLUSION: Inter-observer reliability was better for TJCs than SJCs. Regarding SJCs agreement was better in large joints such as the knees compared to the small joints such as the MCPs. Disease global assessment may show discrepancy between patients and physicians.
28352145 Methotrexate Reduced TNF Bioactivity in Rheumatoid Arthritis Patients Treated with Inflixi 2017 Objectives. To evaluate methotrexate effect on tumor necrosis factor (TNF) alpha bioactivity during infliximab (IFX) therapy in rheumatoid arthritis (RA) patients and to correlate TNF bioactivity with antibody towards IFX (ATI) development and RA clinical response. Materials and Methods. Thirty-nine active women RA patients despite conventional synthetic disease modifying antirheumatic drugs (csDMARDs) requiring IFX therapy were enrolled, and clinical data and blood samples were recorded at baseline (W0) and at 6 weeks (W6), W22, and W54 of IFX treatment. TNF bioactivity as well as IFX trough and ATI concentrations were assessed on blood samples. Results. TNF bioactivity decreased from W0 to W54 with a large range from W22 at the time of ATI detection. From W22, TNF bioactivity was lower in presence of methotrexate as csDMARD compared to other csDMARDs. IFX trough concentration increased from W0 to W54 with a large range from W22, similarly to TNF bioactivity. Methotrexate therapy prevented ATI presence at W22 and reduced TNF bioactivity compared to other csDMARDs (p = 0.002). Conclusion. This suggests that methotrexate plays a key role in TNF bioactivity and against ATI development.
28750350 Is macrophage polarization important in rheumatoid arthritis? 2017 Sep Macrophages are myeloid immune cells which are strategically positioned throughout the body, where they engulf and degrade debris, dead cells, and foreign substances, and coordinating the inflammatory processes. Macrophages can be divided into two extreme subsets, classical activation (M1), and alternatively activation (M2). The symptoms and signs of rheumatoid arthritis (RA) would exacerbate with the increase in pro-inflammatory cytokines, whereas anti-inflammatory cytokines will alleviate the symptoms and signs of RA. This review, mainly discusses the effects of Notch, JNK and ERK signaling pathways on the regulation of macrophage polarization, and the effects of pro-inflammatory factors and/or anti-inflammatory cytokines produced by polarized macrophages in RA. Also, we will make an attempt to find out the importance of macrophage polarization in RA treatment as a drug target.
27163292 The growth factor midkine may play a pathophysiological role in rheumatoid arthritis. 2017 Jan OBJECTIVES: Midkine (MK) is involved in cell proliferation, differentiation, migration, and survival. In this study, we measured serum MK levels in rheumatoid arthritis (RA) and investigated the correlation of serum MK with RA disease activity. Expression and effect of MK in RA synovial tissue were also examined. METHODS: Serum MK and production of inflammatory mediators by rheumatoid synovial fibroblasts (RSFs) were measured by enzyme-linked immunosorbent assay. MK expression in synovial tissue was examined by immunohistochemistry. MK receptor expression was analyzed by RT-PCR and Western blotting. RESULTS: RA patients had a significantly higher serum MK level than healthy controls. In RA patients, the MK level was correlated with DAS28-ESR, disability index of the Health Assessment Questionnaire, and rheumatoid factor level. The serum MK level tended to be decreased by anti-TNF therapy. MK was expressed by synovial lining cells in RA synovial tissues and it enhanced the production of IL-6, IL-8, and CCL2 by RSFs. RSFs expressed LDL receptor-related protein 1, candidate receptor for MK. CONCLUSIONS: The serum MK level could be a marker of disease activity in RA and an indicator of a poor prognosis. MK may have a role in the pathogenesis of RA via induction of inflammatory mediators.
27483042 Advanced oxidation protein products induce apoptosis of human chondrocyte through reactive 2017 Feb Advanced oxidation production products (AOPPs) have been confirmed to accumulate in patients with rheumatoid arthritis (RA). Previous study demonstrated that AOPPs could accelerate cartilage destruction in rabbit arthritis model. However, the effect of AOPP stimulation on apoptosis of human chondrocyte and the underlying mechanisms remains unclear. This study demonstrated that exposure of chondrocyte to AOPPs resulted in cell apoptosis. AOPP stimulation triggered reactive oxygen species (ROS) production, which induced mitochondrial dysfunction and endoplasmic reticulum stress (ER stress) resulted in caspase activation. Furthermore, an antioxidant, N-acetylcysteine, markedly blocked these signals. Our study demonstrated that AOPPs induce apoptosis via ROS-related mitochondria- and ER-dependent signals in human chondrocyte. Targeting AOPP-triggered ROS generation might be as a promising option for patients with RA.
29106059 Increased levels of neutrophil extracellular trap remnants in the serum of patients with r 2018 Feb AIMS: Neutrophil extracellular traps (NETs) comprise a unique form of non-apoptotic cell death exhibited by neutrophils, which occurs in a stepwise process termed NETosis. It has been postulated that NETosis plays an important role in the pathogenesis of autoimmune disorders. The aim of this study was to evaluate serum levels of NET remnants in patients with rheumatoid arthritis (RA), as well as potential associations between NET remnants and indicators of RA. METHODS: Serum levels of myeloperoxidase (MPO)-DNA complexes (NET remnants) were examined in 74 RA patients and 50 healthy controls using a modified enzyme-linked immunosorbent assay. Associations between the levels of these complexes and indicators of RA were then statistically evaluated. RESULTS: RA patients exhibited significantly higher levels of MPO-DNA complexes than the healthy controls, and these levels were associated with increased neutrophil counts and positivity for rheumatoid factor (RF) and anti-citrullinated protein/peptide antibodies (ACPA). Among the 63 ACPA-positive RA patients examined, those with ACPA titers > 1600 U/mL showed significantly increased MPO-DNA levels. Receiver operating characteristic analysis determined that the area under the curve for all 74 RA patients was 0.798, with a sensitivity of 91.9% and a specificity of 56.0%, while that for the ACPA-negative patients was 0.891, with a sensitivity and specificity of 81.8% and 84.0%, respectively. CONCLUSIONS: The results of this study suggest that the disease status of RA is associated with increased NETosis. In particular, evaluation of serum MPO-DNA levels may comprise a useful complementary tool for discriminating RA patients from healthy individuals.
27837340 Comorbidity of gout and rheumatoid arthritis in a large population database. 2017 Mar Coexistence of rheumatoid arthritis and gout is considered to be unusual. The current study was designed as a population-based cross-sectional study, utilizing the medical database of Clalit Health Services, the largest healthcare provider organization in Israel. Data of adult patients who were previously diagnosed with rheumatoid arthritis was retrieved. For each patient, five age- and sex-matched control patients were randomly selected. Different parameters including BMI, socioeconomic status, and existence of gout as well as smoking and hypertension were examined for both groups. The study included 11,540 patients with rheumatoid arthritis and 56,763 controls. The proportion of gout in the study group was high compared to controls (1.61 vs. 0.92%, P < 0.001). In a multivariate analysis, rheumatoid arthritis was associated with gout (OR = 1.72, 95% CI 1.45-2.05, P = 0.00). The proportion of gout in rheumatoid arthritis patients is not lower than in the general population.
28279294 Association Between Rheumatoid Arthritis and Risk of Ischemic and Nonischemic Heart Fai 2017 Mar 14 BACKGROUND: It is unknown whether the increased risk of heart failure (HF) in rheumatoid arthritis (RA) is independent of ischemic heart disease (IHD). OBJECTIVES: This study sought to investigate the relative risk of HF overall and by subtype (ischemic and nonischemic HF) in patients with RA and to assess the impact of RA disease factors. METHODS: Two contemporary cohorts of RA subjects were identified from Swedish patient and rheumatology registries and matched 1:10 to general population comparator subjects. A first-ever HF diagnosis (classified as ischemic HF or nonischemic HF based on the presence of IHD) was assessed through registry linkages. Relative risks for a history of HF before RA onset were calculated through odds ratios. Relative risks of incident HF in RA were calculated as hazard ratios (HRs). RESULTS: By the time of RA onset, a history of HF was not more common in RA. In the new-onset RA cohort, the overall HRs for subsequent HF (any type), ischemic HF, and nonischemic HF were between 1.22 and 1.27. The risk of nonischemic HF increased rapidly after RA onset, in contrast to the risk of ischemic HF. High disease activity was associated with all HF types but was most pronounced for nonischemic HF. In the cohort of patients with RA of any duration, the HRs were between 1.71 and 1.88 for the different HF subtypes. CONCLUSIONS: Patients with RA are at increased risk of HF that cannot be explained by their increased risk of IHD. The increased risk of nonischemic HF occurred early and was associated with RA severity.
28075155 A Qualitative Study Exploring Community Yoga Practice in Adults with Rheumatoid Arthritis. 2017 Jun OBJECTIVE: Yoga may improve physical function and reduce disease symptoms in adults with rheumatoid arthritis (RA). However, little is known about how patients with RA are practicing yoga in the community. The objective of this qualitative study was to explore community yoga practice characteristics and thoughts about yoga practice for adults with RA. DESIGN: Participants completed a semi-structured telephone interview with open-ended questions. Thematic analysis was used to analyze interview transcripts. PARTICIPANTS: A convenience sample of 17 adults with rheumatologist-diagnosed RA who had participated in yoga within the past year were asked about the decision to start, continue, and stop yoga; the perceived benefits of yoga; components of yoga sessions; and general thoughts about yoga as it relates to RA. RESULTS: Although eight different styles of yoga were practiced, commonalities in yoga class components (such as stretching, strengthening, deep breathing, meditation, and positive messaging from the instructor) reveal examples of preferred types of yoga for patients with RA. Three main themes emerged, each with multiple subthemes: (1) motivators (physical fitness, influence of others, reduced price), (2) barriers (cost, symptom burden, class difficulty), and (3) benefits of yoga practice (mind-body, a tool for coping, pride/achievement, social, and "yoga meets you where you are"). CONCLUSION: In this study, patients with RA described how yoga practice helped improve physical and psychosocial symptoms related to their disease. Yoga practice, a dynamic exercise, encompassing many different styles, can provide many benefits for adults with RA; however, yoga may not be beneficial for every adult with RA.
28821374 IL-17 Production of Neutrophils Enhances Antibacteria Ability but Promotes Arthritis Devel 2017 Sep To our knowledge, no studies have examined the role of IL-17 production by neutrophils in immune defense against Mycobacterium tuberculosis (MTB) infection and the pathogenesis of rheumatoid arthritis (RA) caused by MTB infection. Here, we determined that neutrophils express IL-17 in an autocrine IL-6- and IL-23-dependent manner during MTB infection. MTB H37Rv-induced IL-6 production was dependent on the NF-κB, p38, and JNK signaling pathways; however, IL-23 production was dependent on NF-κB and EKR in neutrophils. Furthermore, we found that Toll-like receptor 2 (TLR2) and TLR4 mediated the activation of the kinases NF-κB, p38, ERK, and JNK and the production of IL-6, IL-23, and IL-17 in neutrophils infected with MTB H37Rv. Autocrine IL-17 produced by neutrophils played a vital role in inhibiting MTB H37Rv growth by mediating reactive oxygen species production and the migration of neutrophils in the early stages of infection. However, IL-17 production by neutrophils contributed to collagen-induced arthritis development during MTB infection. Our findings identify a protective mechanism against mycobacteria and the pathogenic role of MTB in arthritis development.
28841363 Tocilizumab (Actemra). 2017 Sep 2 Tocilizumab (TCZ), is a recombinant humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody which has a main use in the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis (sJIA) and polyarticular juvenile idiopathic arthritis (pJIA). This article provides an overview of TCZ including looking into the past at the discovery of interleukin-6 (IL-6) as a pro-inflammatory cytokine. It also looks at how tocilizumab was developed, manufactured and tested to ensure both safety and efficacy in a human population. The article then explores the advantages and disadvantages of using TCZ when compared to other biologics approved in RA, sJIA and pJIA and finally looks ahead to the future and the emerging role of IL-6 and its blockade by TCZ as a treatment for giant cell arteritis (GCA), polymyalgia rheumatica (PMR) and large vessel vasculitis (LVV).
29141925 Unusual Salmonella typhi periprosthetic joint infection involving bilateral knees: managem 2017 Nov 14 A 70-year-old Indian woman, who had undergone primary bilateral total knee arthroplasty (TKA) for rheumatoid arthritis 10 months prior, presented with 10 days history of pain, swelling and erythema over both knees with pus discharging from the right knee. She had type 2 diabetes mellitus and was on long-term steroid, leflunomide and antitumour necrosis factor therapy for rheumatoid arthritis. Her clinical and laboratory features were suggestive of a haematogenous periprosthetic joint infection (PJI). The final diagnosis of bilateral Salmonella typhi PJI was made based on culture reports. Considering her underlying immunosuppression, a bilateral two-stage revision TKA was done with complete remission of symptoms and good functional recovery at last follow-up after 18 months. S. typhi infection of prosthetic joint has not been reported in the literature. Patients presenting with gastrointestinal complaints and PJI should alert the clinician to the possibility of infection with such atypical organisms endemic to the region.
28220341 Adenovirus-Mediated Small Interfering RNA Targeting TAK1 Ameliorates Joint Inflammation wi 2017 Jun Transforming growth factor β-activated kinase-1 (TAK1) is a key upstream kinase in cell signaling during inflammation, which regulates the expression of inflammatory mediators. Small interfering RNA (siRNA) against TAK1 offers promise as a potential therapeutic strategy in immune-mediated inflammatory disorder including rheumatoid arthritis. Here, we are to evaluate the therapeutic effects of intra-articular administration of adenoviral-mediated siRNA against TAK1 (ad-siRNA-TAK1) on collagen-induced arthritis (CIA) in mice. Ad-siRNA-TAK1 was constructed. The murine RAW 264.7 macrophages were infected with ad-siRNA-TAK1, and the silencing specificity of TAK1 was assessed by quantitative polymerase chain reaction (PCR) and western blot. DBA/1 mice were injected intra-articularly with ad-siRNA-TAK1. Development and severity of arthritis was assessed histologically. Synovial inflammation and bone destruction were determined by hematoxylin and eosin (HE) staining. Articular and serum concentrations of tumor necrosis factor-α, interleukin-1, and interleukin-6 were determined using enzyme-linked immunosorbent assay. Levels of phosphorylated p38, c-Jun N-terminal kinase (JNK), and extracellular-signal-regulated kinase (ERK) were detected by western blot. In vitro, ad--siRNA-TAK1 efficiently inhibited the expression of TAK1 at both mRNA and protein levels. In vivo, intra-articular injection of ad-siRNA-TAK1 efficiently alleviated joint inflammation, decreased the expression of pro-inflammatory mediators, and suppressed JNK pathways. Our results demonstrate the efficiency of ad--siRNA-TAK1 in controlling joint inflammation of CIA, which is associated with the suppression of the expression of pro-inflammatory cytokines and JNK activation.
27998030 Associations Between Five Important Domains of Health and the Patient Acceptable Symptom S 2017 Oct OBJECTIVE: To explore the link between a patient acceptable symptom state (PASS) and patient-perceived impact in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: This was a cross-sectional study of unselected patients with definite RA or PsA. Pain, functional capacity, fatigue, coping, and sleep disturbance were assessed using a numeric rating scale (0-10) and compared between patients in PASS or not (Cohen's effect sizes). The domains of health associated with PASS status were assessed by multivariate forward logistic regression, and PASS thresholds were determined using the 75th percentile method and receiver operating characteristic analyses. RESULTS: Among 977 patients (531 with RA, 446 with PsA), the mean ± SD age was 53.4 ± 13.2 years, mean ± SD disease duration was 11.2 ± 10.0 years, and 637 (65.8%) were women. In all, 595 patients (60.9%) were in PASS; they had lower symptom levels, and all domains of health except sleep disturbance discriminated clearly between patients in PASS or not (effect sizes 0.73-1.45 in RA and 0.82-1.52 in PsA). In multivariate analysis, less pain and better coping were predictive of being in PASS. Odds ratios were: RA pain 0.80 (95% confidence interval [95% CI] 0.67-0.96), PsA pain 0.63 (95% CI 0.52-0.75), RA coping 0.84 (95% CI 0.74-0.96), and PsA coping 0.83 (95% CI 0.71-0.97). The cutoffs of symptom intensity (range 0-10), corresponding to PASS for the 5 domains of health and the 2 diseases were similar, i.e., approximately 4-5. CONCLUSION: In RA and PsA, PASS was associated with the 5 domains of health analyzed, and in particular with less pain and better coping.
29175592 Role of extracellular vesicles in rheumatoid arthritis. 2018 Jan Cell-derived extracellular vesicles (EVs) are involved in the pathogenesis of rheumatoid arthritis (RA), playing important roles in antigen presentation, inflammation, angiogenesis, cell-cell signal communication, thrombosis, and articular cartilage extracellular matrix degradation. Understanding the pathogenic mechanism of RA is important for developing therapies. The pathogenic indicators of RA, such as submicron-sized EVs, represent promising biomarkers for evaluating RA activity. This review summarizes the recent advances in understanding the pathogenesis of RA, and sheds light on the pathogenic as well as anti-inflammatory or immunosuppressive roles of EVs. We suggest that EVs could be harnessed as tools for drug delivery or targets for RA therapies.
27796523 Adaptation and validation of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnair 2017 Apr Rheumatoid arthritis (RA) is one of the most prevalent inflammatory rheumatic diseases. As it is a chronic and a lifelong destructive disease, the aim of the treatment is to reduce disability and improve quality of life. The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is a patient-reported outcome measure, specific to RA. To adapt and validate the RAQoL for use in Serbia, two translation panels were involved to produce the Serbian RAQoL. After successful translation, face and content validity was determined via cognitive debriefing interviews. The psychometric properties of the questionnaire were examined, including reliability and construct validity, by using the Nottingham Health Profile (NHP) as a comparator scale. The RAQoL was translated successfully and rated as applicable, relevant and comprehensive by respondents. The questionnaire had high internal consistency (alpha = 0.94 at both time points) and test-retest reliability (r = 0.92). Moderately high correlations were found between the RAQoL and physical mobility, pain and energy level sections of the NHP, providing evidence of convergent validity. The RAQoL was able to distinguish between patients grouped by perceived general health, incidence of flare-up and disease severity. The Serbian language version of the RAQoL showed strong evidence of reliability and validity and is recommended for use in clinical trials and routine general practice in RA.
28108005 In vitro allogeneic immune cell response to mesenchymal stromal cells derived from human a 2017 Apr We investigated the regulatory activity of human adipose-derived mesenchymal stromal cells (MSCs) (n=10) towards immune cells in a cohort of 84 rheumatoid arthritis (RA) patients, 36 apparently healthy controls. We co-cultured MSCs with lymphocyte subsets of T, B, and T regulatory cells (Tregs). Levels of the pro- and anti-inflammatory markers (tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and interleukin-10 (IL-10)) were estimated in serum and co-culture supernatants. The study revealed a two-fold increase in the proportion of Tregs and an increased level of CD4(+)CD25(+)FoxP3. MSCs altered T cell, B cell, and Treg cytokine production during an anti-inflammatory immune response. The MSCs inhibited CD3+T cell-mediated TNF-α secretion, upregulated IL-10, and suppressed the production of autoantibodies against citrullinated protein antigens produced by B cells. These data offer insight into the interactions between allogeneic MSCs and immune cells, and elucidate the dose-dependent modulation of MSCs.