Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
33249794 Highlights in Autoimmunity: 2020. 2020 Nov Innate and adaptive immune response dysregulations are equally involved in the induction of autoimmunity. Toll-like receptors play a leading role in the activation of innate immune cells, thus priming auto-reactive T cells. Th17 cells and related cytokines are widely involved in many immune-mediated diseases such as rheumatoid arthritis. Thus, the recent introduction of anti-IL-17 therapies should be further evaluated. Janus kinase inhibitors and Fc receptor-targeting drugs are some of the new therapeutic strategies that are being implemented when old classical therapies lack sufficient beneficial outcomes.
32459816 Risk for development of inflammatory bowel disease under inhibition of interleukin 17: A s 2020 OBJECTIVE: Cases of inflammatory bowel disease (IBD) during treatment with interleukin (IL)-17 antagonists have been reported from trials in psoriasis, psoriatic arthritis, and ankylosing spondylitis. The aim of this study was to assess the overall risk for development of IBD due to IL-17 inhibition. DESIGN: Systematic review and meta-analysis of studies conducted 2010-2018 of treatment with IL-17 antagonists in patients with psoriasis, psoriatic arthritis, ankylosing spondylitis, and rheumatoid arthritis. We compared risk of IBD development in anti-IL-17 treated patients compared to placebo treatments. We also computed incident rates of IBD overall. A 'worst case scenario' defining subjects ambiguous for prevalent versus incident cases for the latter was also applied. RESULTS: Sixty-six studies of 14,390 patients exposed to induction and 19,380 patients exposed to induction and/or maintenance treatment were included. During induction, 11 incident cases of IBD were reported, whereas 33 cases were diagnosed during the entire treatment period. There was no difference in the pooled risk of new-onset IBD during induction studies for both the best-case [risk difference (RD) 0.0001 (95% CI: -0.0011, 0.0013)] and worst-case scenario [RD 0.0008 (95% CI: -0.0005, 0.0022)]. The risk of IBD was not different from placebo when including data from maintenance and long-term extension studies [RD 0.0007 (95% CI: -0.0023, 0.0036) and RD 0.0022 (95% CI: -0.0010, 0.0055), respectively]. CONCLUSIONS: The risk for development of IBD in patients treated with IL-17 antagonists is not elevated. Prospective surveillance of patients treated with IL-17 antagonists with symptom and biomarker assessments is warranted to assess for onset of IBD in these patients.
31624331 Predictive genetic biomarkers for the efficacy of methotrexate in rheumatoid arthritis: a 2020 Apr Multiple pharmacogenetic studies investigated the effectiveness of methotrexate. However, due to the use of nonvalidated outcomes, lack of validation or conflicting results it remains unclear if genetic markers can help to predict response to MTX treatment. Therefore, a systematic review was performed. PubMed was searched for articles reporting potential pharmacogenetic biomarkers associated (p < 0.05) with MTX efficacy using the validated endpoints DAS(28), EULAR, or ACR response criteria. The PICO method was used for study selection, and PRISMA guidelines to prepare the report. Thirty-five studies met the inclusion criteria, providing 39 potential genetic biomarkers in 19 genes. After Bonferroni correction, six genetic biomarkers were associated with the efficacy of MTX: ATIC rs7563206; SLC19A1 rs1051266; DHFR rs836788; TYMS rs2244500, rs2847153, and rs3786362 in at least one study. Only SLC19A1 rs1051266 was replicated in an independent cohort and promising for predicting methotrexate efficacy.
32181696 Contribution of tenosynovitis of small joints to the symptom morning stiffness in patients 2020 May Objective: Morning stiffness (MS) is characteristic of rheumatoid arthritis (RA). Despite its association with functional disability, the extent to which local inflammatory processes contribute to this symptom is unknown. Magnetic resonance imaging (MRI)-detected tenosynovitis of small joints is recognized as an early feature of RA, which is also associated with functional impairments. It has been proposed that tenosynovitis contributes to MS. Therefore, we assessed the relationship between MS and MRI-detected inflammation, in particular tenosynovitis.Method: In total, 286 consecutive patients newly presenting with undifferentiated arthritis and RA underwent contrast-enhanced 1.5 T MRI of (2-5) metacarpophalangeal, wrist, and (1-5) metatarsophalangeal joints. Scans were scored for tenosynovitis according to Haavardsholm, and for synovitis by Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS). MS was dichotomized as ≥ 60 min or not. Associations between MS and tenosynovitis/synovitis were tested with logistic regression, data were categorized (solitary or simultaneous presence of synovitis/tenosynovitis), and the presence of an additive interaction was assessed.Results: MS was present in 40% of patients. Tenosynovitis was more often present in patients with MS than without MS [80% vs 65%, odds ratio (OR) 2.11, 95% confidence interval (1.21;3.69)]. Synovitis was more often present in patients with MS [58% vs 44%, OR 1.79 (1.11;2.91)]. In categorized analyses, concurrent synovitis and tenosynovitis had the largest association [OR 2.43 (1.30;4.54)], in contrast to solitary synovitis [OR 0.85 (0.21;3.47)]. The additive interaction was non-significant. The variance explained in all analyses was small (range 4-5%).Conclusion: Tenosynovitis, combined with synovitis, at small joints is associated with MS and contributes to the pathophysiology of MS.
32831126 Linking the effect of psoriatic arthritis-related foot involvement to the Leeds Foot Impac 2020 Aug 24 BACKGROUND: Previous research to describe the impact of foot involvement in psoriatic arthritis has used the Leeds Foot Impact Scale in Rheumatoid Arthritis (LFIS-RA) in the current absence of any psoriatic arthritis foot-specific tools. However, the LFIS-RA is a rheumatoid arthritis disease-specific outcome measure and its content validity for evaluating the experiences of people with psoriatic arthritis-related foot involvement is unknown. The study objective was to determine the content validity of the LFIS-RA for assessing people with psoriatic arthritis, using the International Classification of Functioning, Disability and Health (ICF) as the frame of reference. METHOD: Concepts within each item of the LFIS-RA were linked to the best-matched ICF categories using established linking rules, which enable a systematic and standardised linking process. All concepts were independently linked to the ICF by 2 investigators with different professional backgrounds, which included occupational therapy and podiatry. The list of ICF categories derived from previous research that pertained to the foot in psoriatic arthritis was then compared with the ICF categories linked to the LFIS-RA. The comparison was undertaken in order to determine the extent to which concepts important and relevant to people with psoriatic arthritis-related foot involvement were addressed. RESULTS: Thirty-five distinct ICF categories were linked to the LFIS-RA, which related to body functions (44%), activities and participation (35%), environmental factors (16%) and body structure (5%). In comparison with the ICF categories derived from concepts of the foot in psoriatic arthritis previously defined, the LFIS-RA provided coverage of key constructs including pain, functioning, daily activities, footwear restrictions and psychological impact. Other concepts of importance in psoriatic arthritis such as skin and toenail involvement, self-management and paid employment were not addressed in the LFIS-RA. CONCLUSION: Content validity of the LFIS-RA to determine the impact of foot functional impairments and disability in people with psoriatic arthritis was not supported by the results of this study. Future work should consider the development of a psoriatic arthritis foot-specific patient reported outcome measure, using the LFIS-RA as an important foundation.
31876120 Generation of Distinct Patterns of Rheumatoid Arthritis Autoantigens by Peptidylarginine D 2020 Jun OBJECTIVE: To address the independent roles of peptidylarginine deiminase type 2 (PAD2) and PAD4 in generating rheumatoid arthritis (RA) autoantigens by using a system that mimics intracellular citrullination in the RA joint. METHODS: PAD2- or PAD4-expressing 293T cells and mock-transfected cells were used as targets in cytotoxic assays using lymphokine-activated killer cells, cytotoxic YT cell granule contents, or purified human perforin. Protein citrullination and autoantigen production were determined by immunoblotting using the anti-modified citrulline-Senshu method and RA sera (n = 30), respectively. RESULTS: RA sera recognized at least 3 categories of autoantigens in PAD-expressing target cells killed by the cytotoxic lymphocyte granule-induced death pathway. These included: 1) autoantigens targeted in their native form, 2) citrullinated antigens, and 3) antigens cleaved by cytotoxic proteases (e.g., granzymes). Interestingly, although target cells expressing PAD2 or PAD4 showed prominent hypercitrullination of a broad range of proteins during cytotoxic granule-induced cell damage, autoantibodies in RA sera targeted only a very limited number of antigens in hypercitrullinated cells. Furthermore, RA sera showed distinct reactivities to autoantigens generated by PAD2 or PAD4. CONCLUSION: The cytotoxic granule-induced death pathway has the capacity to modify antigens by inducing hypercitrullination and antigen cleavage in target cells. Interestingly, among a large number of citrullinated proteins generated by PAD2 and PAD4 in cells, only a few are likely involved in the production of autoantibodies in RA.
32514679 Characteristics of Chikungunya virus infection in patients with established rheumatoid art 2020 Dec The aim of this study is to describe both clinical and treatment needs in six patients who had a previous diagnosis of rheumatoid arthritis (RA) and were infected with Chikungunya virus (CHIKV). We report RA patients who acquired CHIKV infection, treated from the Fundación Valle del Lili Hospital, Cali, Colombia, between August 2014 and September 2015. Data of demographic information, clinical and laboratory findings, DAS28 score, dose of glucocorticoids (GC), or conventional or DMARD use was collected before, during CHIKV infection, and 6 months of follow-up. Five women and one man were analyzed, with an average age of 66 years, who had been receiving low doses of GC (4 mg of prednisolone/day on average). Two patients were being treated with methotrexate (MTX) and etanercept, one with MTX and other with etanercept, with an average DAS28 of 2.00 at the last control consultation. At the time of CHIKV infection, they presented an average DAS28 of 3.98, requiring more than double their usual dose of GC (average dose 8.75 mg/day of prednisolone). One patient required a change from etanercept to adalimumab and three others started rituximab, tocilizumab, and tofacitinib as second-line medication. A case series of patients with RA in remission are presented, who when contracting CHIKV infection developed exacerbation of their underlying disease, which in general was difficult to control. An increase in the doses of GC and change or induction to the use of second-line medications (anti-TNF, anti-CD20, or Janus kinase inhibitor) were required. Key Points • The clinical outcome of RA patients with CHIKV infections is not well known. • A group of RA patients, who were in clinical remission, were affected during the 2014-2015 CHIKV epidemic and treated in a hospital in southwestern Colombia, and had severe reactivation of their RA. • Some patients with RA in remission and who had CHIKV infection required an increase in the glucocorticoid, in addition to starting second-line medications (anti-TNF, anti-CD20, or Janus kinase inhibitor) or their modification.
33026178 Disease severity affects myocardial functions in patients with treatment-naive early rheum 2021 Apr OBJECTIVES: The cross-sectional study aimed to assess myocardial functions using global longitudinal strain (GLS) echocardiography and arrhythmia parameters with treatment naive newly diagnosed rheumatoid arthritis (RA) and no clinical evidence of cardiovascular disease (CVD). METHODS: Seventy seven newly diagnosed treatment-naive RA patients were enrolled. Disease severity was evaluated according to rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) positivity, and Disease Activity Score 28 C-reactive protein (DAS28 CRP). Myocardial functions were assessed using conventional echocardiography and GLS technique and electrocardiogram parameters cQT and Tp-e/cQT. RESULTS: Twenty three patients had severe disease while 54 patients were non-severe. The Left Ventricle GLS (17.98 ± 1.24 vs 21.29 ± 1.03, P < .001), cQT (428.71 ± 9.05 vs 394.61 ± 17.83, P < .001), Tp-e/cQT (0.19 ± 0.02 vs 0.16 ± 0.01, P < .001) for severe RA patients was reduced compared to RA non-severe patients. Penalized maximum likelihood estimation logistic regression analysis revealed LVGLS as the only significantly independent predictor of severe RA disease (OR 0.70, CI 95% 0.52-0.92, P = .001). Receiver operating characteristic (ROC) curves of the LVGLS was revealed 19.9 as GLS discriminative value with 88.8% positive predictive value for predicting severity. Severe RA risk increases when log-odds value was over 0, corresponds to LVGLS value less than 18 by partial effect plots. CONCLUSION: RA severity was associated with lower LV systolic myocardial function and increased arrhythmia parameters. Only LVGLS was significantly independent predictor of RA disease severity.
32249644 Mortality of Sepsis in Patients With Rheumatoid Arthritis: A Single-Center Retrospective A 2021 Jul INTRODUCTION/BACKGROUND: Patients with rheumatoid arthritis (RA) have a high risk of infections that may require intensive care unit (ICU) admission in case of resulting sepsis. Data regarding the mortality of these patients are very limited. This study investigated clinical characteristics and outcomes of patients with RA admitted to the ICU for sepsis and compared the results to a control cohort without RA. METHODS: All patients with RA as well as sex-, age-, and admission year-matched controls admitted to the ICU of a university hospital for sepsis between 2006 and 2019 were retrospectively analyzed. Mortality was calculated for both the groups, and multivariate logistic regression was used to determine independent risk factors for sepsis mortality. The positive predictive value of common ICU scores was also investigated. RESULTS: The study included 49 patients with RA (mean age 67.2 ± 9.0 years, 63.3% females) and 51 matched controls (mean age 67.4 ± 9.5 years, 64.7% females). Among the patients with RA, 42.9% (n = 21) were treated with conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and 30.6% (n = 15) received glucocorticoids only. Seven (14.3%) patients received biologic (b) DMARDs. The hospital mortality was higher among patients with RA (42.9% vs 15.7%, P = .0016). Rheumatoid arthritis was independently associated with mortality in multivariate logistic regression (P = .001). In patients with RA, renal replacement therapy (P = .024), renal failure (P = .027), and diabetes mellitus (P = .028) were independently associated with mortality. Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology Score II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores were good predictors of sepsis mortality in patients with RA (APACHE II area under the curve [AUC]: 0.78, P = .001; SAPS II AUC: 0.78, P < .001; SOFA AUC 0.78, P < .001), but their predictive power was higher among controls. CONCLUSIONS: Hospital sepsis mortality was higher in patients with RA than in controls. Rheumatoid arthritis itself is independently associated with an increased sepsis mortality. Renal replacement therapy, renal failure, and diabetes were associated with an increased mortality. Common ICU scores were less well predictors of sepsis mortality in patients with RA compared to non-RA controls.
32681975 Pop a pill or give myself a shot? Patient perspectives of disease-modifying anti-rheumatic 2021 Jan OBJECTIVE: To assess how patients with rheumatoid arthritis (RA) decide whether to add oral disease-modifying anti-rheumatic drugs (DMARDs) versus injectable biologic DMARDs when methotrexate response is inadequate. METHODS: Using nominal group technique (NGT), RA patients answered the question "What sort of things are important to you when you make a decision between adding pills versus injectable medications to treat rheumatoid arthritis when methotrexate fails to control RA disease activity?" Patients nominated, discussed, and voted for the responses. RESULTS: Forty-seven RA patients participated: Birmingham (n=6 NG; 21 patients) and New York City (n=4 NG; 26 patients). They were predominantly female (85%), 70% white, with a mean age of 64.5 years and 58% had>10-year RA duration. Present/past DMARDs included methotrexate only in 6%, other traditional DMARDs in 15%, glucocorticoids in combination with traditional DMARDs in 11%, and biologics and/or Jak-kinase inhibitors in 68% of participants. Voted domains in order were: (1) efficacy/effectiveness and the onset/mode of action (78/282 votes); (2) side effects/fear of side effects (84/282 votes); (3) cost including out of pocket, co-payments and patient responsibility (54/282 votes); (4) convenience/frequency of use (27/282 votes); (5) doctor's opinion (20/282 votes); (6) other drugs/comorbidity/other patient's experience/effects on other people (3/282 votes); (7) fear of needles (8/282 votes); and (8) newness of the medication (8/282 votes). CONCLUSIONS: We identified the patient perspective regarding the choice between adding oral versus injectable DMARD once methotrexate failed to control RA disease activity. This knowledge can help in shared decision-making for DMARD choice in RA treatment.
32145086 TRIM32 promotes inflammatory responses in rheumatoid arthritis fibroblast-like synoviocyte 2020 Jun Rheumatoid arthritis (RA) is a worldwide autoimmune disease. The study of its aetiology and mechanism has always been a focus topic in medicine. This research was designed to investigate the effect of E3 ubiquitin ligase tripartite motif protein 32 (TRIM32) in rheumatoid arthritis (RA). We found in fibroblast-like synoviocytes (FLS) of RA patients, the expression of TRIM32 was significantly increased compared with its expression in osteoarthritis (OA) patients FLS. A widely used pro-inflammatory stimuli tumour necrosis factor-alpha (TNF-α) was found to promote TRIM32 expression in a time-dependent manner. Furthermore, we observed that overexpression of TRIM32 aggravated the production of pro-inflammatory cytokines in FLS, silencing of TRIM32 showed the consistent results. In addition, TRIM32 was found to activate nuclear factor κB (NF-κB) signalling pathway, and TRIM32 could interact with TNF receptor-associated factor 2 (TRAF2) to promote the K63-linked polyubiquitination of TRAF2 in RA-FLS. In conclusion, we suggested that TRIM32 as a positive regulator of inflammatory responses in RA-FLS.
31892533 Efficacy and safety of NI-0101, an anti-toll-like receptor 4 monoclonal antibody, in patie 2020 Mar OBJECTIVES: Anti-citrullinated protein antibodies (ACPAs) form immune complexes with citrullinated proteins binding toll-like receptor (TLR) 4, which has been proposed as a mediator of rheumatoid arthritis (RA). NI-0101 is a first-in-class humanised monoclonal antibody blocking TLR4, as confirmed by inhibition of in vivo lipopolysaccharide-induced cytokine release in healthy volunteers. This study was design to confirm preclinical investigations supporting a biomarker-driven approach for treatment of patients with RA who present positive for these immune complexes. METHODS: Placebo-controlled, double-blind, randomised (2:1) trial of the tolerability and efficacy of NI-0101 (5 mg/kg, every 2 weeks for 12 weeks) versus placebo in ACPA-positive RA patients with inadequate response to methotrexate. Efficacy measures included Disease Activity Score (28-joint count) with C reactive protein (DAS28-CRP), European League Against Rheumatism (EULAR) good and moderate responses, and American College of Rheumatology (ACR) 20, ACR50 and ACR70 responses. Subgroup analyses defined on biomarkers were conducted. Pharmacokinetics, pharmacodynamics and safety were reported. RESULTS: 90 patients were randomised (NI-0101 (61) and placebo (29)); 86 completed the study. No significant between-group difference was observed for any of the efficacy endpoints. Subgroup analyses using baseline parameters as covariants did not reveal any population responding to NI-0101. Treatment-emergent adverse events occurred in 51.7% of patients who received placebo versus 52.5% for NI-0101. CONCLUSIONS: We demonstrate for the first time that in RA, a human immune-mediated inflammatory disease, blocking the TLR4 pathway alone does not improve disease parameters. Successful targeting of innate immune pathways in RA may require broader and/or earlier inhibitory approaches.
31486697 Autophagy promotes citrullination of VIM (vimentin) and its interaction with major histoco 2020 May We aimed to investigate the involvement of macroautophagy/autophagy in autoimmunity in rheumatoid arthritis (RA) through citrullination of VIM (vimentin) and its interaction with MHC class II in synovial fibroblasts (SFs). The cell surface expression of MHC class II and B7 costimulatory molecules on SFs was analyzed by flow cytometry after treatment with IFNG/IFN-γ (interferon gamma). Intracellular citrullinated autoantigens in SFs were analyzed by immunoblotting using serum from anti-citrullinated peptide antibodies (ACPA)-positive patient as a primary antibody. SFs were incubated in serum-free medium or treated with proteasome inhibitor MG132 to induce autophagy. An autophagy inhibitor 3-methyladenin (3-MA) was used. Intracellular citrullinated VIM (cVIM) was evaluated by immunoblotting and immunocytochemistry. The interaction between MHC class II and cVIM was evaluated with co-immunoprecipitation and proximity ligation assay (PLA). We demonstrated that MHC class II, CD274/B7-H1 and PDCD1LG2/B7-DC were expressed on SFs following treatment with IFNG whereas CD276/B7-H3 was detected on SFs regardless of the presence of IFNG. ACPA-positive sera recognized a 54 kDa protein in SFs. By immunoprecipitation, the 54 kDa protein recognized by RA sera was revealed to be cVIM. Following induction of autophagy, intracellular cVIM was increased in SFs but the effect was canceled by 3-MA. The interaction between MHC class II and cVIM was demonstrated by co-immunoprecipitation. Furthermore, PLA revealed the significant increase of MHC class II-cVIM interaction following induction of autophagy. Our findings suggest that SFs may contribute to the autoimmunity in RA through citrullination of VIM and its interaction with MHC class II promoted by autophagy.Abbreviations: 3-MA: 3-methyladenine; ACPA: anti-citrullinated peptide antibodies; anti-CCP: anti-cyclic citrullinated peptide antibody; cVIM: citrullinated VIM; BECN1: beclin1; DAPI: 4',6-diamidino-2-phenylindole; FBS: fetal bovine serum; HLA: human leukocyte antigen; IFNG/IFN-γ: interferon gamma; IL6: interleukin 6; IP: immunoprecipitation; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MFI: mean fluorescence index; MHC: major histocompatibility complex; OA: osteoarthritis; PADI: peptidyl arginine deiminase; PepA: pepstatin A; PBS: phosphate-buffered saline; PtdIns3K: phosphatidylinositol 3-kinase; RA: rheumatoid arthritis; SFs: synovial fibroblasts; siRNA: small interfering RNA; VIM: vimentin.
32536125 [Evaluation of the systematic functional rehabilitation on rheumatoid arthritis patients f 2020 Jun 16 Objective: To evaluate the effects of functional rehabilitation on rheumatoid arthritis patients after the total knee arthroplasty (TKA). Methods: Two hundred rheumatoid arthritis patients (259 knees) were enrolled in this study at Arthritis Clinic and Research Center, Peking University People's Hospital from January 2012 to December 2017. All patients received the primary total knee arthroplasty, followed by a systematic functional rehabilitation. The same procedure of rehabilitation was followed, which consisted of patients' education, resistance training, passive and active range of motion exercise, balance exercise, gait training and daily-activity training. According to the degree of postoperative residual flexion contracture, these patients were divided into three groups: the severe (≥30°), moderate(15°-30°), and mild (≤15°). The outcomes of functional rehabilitation were evaluated among different groups and compared with those before the rehabilitation, which included the active range of motion (AROM), the flexion and extension angle of the knee, pain on the visual analogue scale (VAS). The complications and their impacts on the process of rehabilitation were also studied. Independent t test was applied to compare the data before and after the rehabilitaton. Results: There were 17 males (20 knees) and 183 females (239 knees) in this group, aged (57±13) years with a disease course of (16±10) years. There were significant improvements after the functional rehabilitation, including the flexion angle, the extension angle, AROM and pain VAS (76°±12° vs 112°±9°, 12.9°±10.2° vs 2.4°±4.6°, 63°±15° vs 110°±10° and 3.7±1.2 vs 2.0±0.4, respectively; t=39.0, 15.1, 41.3, 21.2, all P<0.01). The residual flexion contracture after the surgery in 259 knees were all improved, among which 195 knees (75.3%) reached a complete correction. Compared with the mild flexion contracture, the moderate and severe group had a lower complete correction rate (80.2% vs 45.9%, χ(2)=20.15, P<0.05). Total of 141 patients (70.5%) suffered from anemia two days after the surgery. By offering the anti-anemia treatment during the systematic rehabilitation, all cases of anemia were healed. The length of hospital stay was longer in the patients with moderate and severe anemia when compared with that in mild anemia ((13±5) days vs (11±5) days, t=2.2, P=0.028). Conclusion: The systematic functional rehabilitation is an effective treatment for rheumatoid arthritis patients after TKA, which can not only help release the pain after surgery, but also assist patients to achieve a better function of the knee.
33033859 Pathological features of established osteoarthritis with hydrathrosis are similar to rheum 2021 May OBJECTIVES: The prevalence of rheumatoid arthritis (RA) and knee osteoarthritis (OA) is increasing with our aging society. Some reports suggest that OA with effusion synovitis develops into RA and early OA patients with effusion are pathologically similar to those with RA. The purpose of this study was to examine the relationship between histological features of established knee OA with or without effusion and RA. METHODS: Seventy-nine patients in which synovial specimens were obtained during total knee arthroplasty were included. Patients were divided into an RA group, OA with effusion (OA+) group, and OA without effusion (OA-) group. The Rooney synovitis score and serum matrix metalloproteinase (MMP)-3 levels were compared among groups. We also examined the correlation between the Rooney synovitis score and its sub-scores with MMP-3 levels. RESULTS: The total Rooney score was significantly higher in the RA group than in the OA+ and OA- groups (25.4 vs 17.1, p < 0.01; 25.4 vs 13.5, p < 0.001, respectively). This score also was significantly higher in the OA+ group than in the OA- group (p < 0.05). The proliferating blood vessels score, perivascular infiltrates of lymphocytes score, focal aggregates of lymphocytes score, and diffuse infiltrates of lymphocytes score were significantly higher in the RA group than in the OA- group (7.05 vs 3.29, 4.95 vs 3.43, 3.29 vs 1.46, and 2.26 vs 1.18, respectively; p < 0.05), but not compared with the OA+ group. The total Rooney score demonstrated a significantly positive correlation with serum MMP-3 levels in the RA group (r = 0.61; 95% CI: 0.28 to 0.81; p < 0.01) and in the OA+ group (r = 0.57; 95% CI: 0.24 to 0.78; p < 0.01). CONCLUSIONS: Previous reports showed the histological similarity between RA and early OA with effusion. We confirmed this histological similarity, in particular the distribution of lymphocytes, between RA and established OA with effusion. It is possible that cases diagnosed as OA with effusion might progress to overt RA. KEY POINTS: • Histological similarity was observed between RA and established OA with effusion.
31729679 Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis. 2020 Mar OBJECTIVE: To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status METHODS: We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO(2), SO(2), particulate matter [PM(2.5), PM(10)], and ozone) from air quality monitoring stations at patients' residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration. RESULTS: The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM(2.5) exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM(2.5) exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers. CONCLUSIONS: In an elderly cohort of RA patients, fine particulate matter (PM(2.5)) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted. Key Points • A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status. • Of different air pollutants measures, exposure to fine particulate matter (PM(2.5)) appears to be most closely linked to ACPA titers.
33124564 Major vault protein/lung resistance related protein: a novel biomarker for rheumatoid arth 2021 Sep OBJECTIVES: Rheumatoid arthritis (RA) can lead to joint destruction and early institution of effective treatment can preserve joint function. Biomarkers can establish early diagnosis and predict effect of treatment. Vault particles, large cytoplasmic ribonucleoprotein particles that participate in inflammation, might serve as biomarkers. The aim of this study was to assess the diagnostic and the prognostic value of major vault protein (MVP) and their antibodies in RA. METHODS: Serum samples from 159 RA patients, 26 early RA (ERA) patients, 21 patients with osteoarthritis (OA) and 30 healthy individuals were tested for MVP, anti-cyclic citrullinated peptide (anti-CCP) and C-reactive protein (CRP) using enzyme-linked immunosorbent assays (ELISA). Rheumatoid factor (RF) was tested by nephelometry, and anti-MVP antibodies were detected by anti-MVP peptide ELISA using an in-house protocol. RESULTS: MVP levels were higher in RA and ERA, compared to OA and healthy controls (p<0.00001). A combination of MVP with RF or anti-CCP showed an improved diagnostic accuracy compared to RF or anti-CCP alone in RA and ERA. MVP exhibited similar AUC levels to anti-CCP and RF in RA whereas in ERA, MVP exhibited the same or slightly higher AUC levels, compared to anti-CCP and RF, respectively. High MVP levels were associated with lack of response to treatment. Levels of anti-MVP peptide 2 antibodies were significantly higher in RA compared to healthy controls (t= 2.73, p=0.007). CONCLUSIONS: MVP and autoantibodies against MVP may have the potential to serve as diagnostic and prognostic biomarkers in RA.
31511979 [Which patients with rheumatoid arthritis do not receive DMARD treatment? Analysis of data 2020 Mar BACKGROUND: The vast majority of patients with rheumatoid arthritis (RA) included in the national database of the German Collaborative Arthritis Centers are treated with disease-modifying antirheumatic drugs (DMARD). The clinical and patient-related characteristics of patients who did not have DMARD treatment in the longer term were investigated. METHODOLOGY: Between 2012 and 2016 a total of 10,289 patients with RA were documented. Patient characteristics, disease activity and severity, comorbidities and concomitant treatment were descriptively evaluated. Patients who were without DMARDs for more than 1 year and not in remission (disease activity score 28, simple disease activity index or Boolean remission) were analyzed separately. Logistic regression was used to investigate which variables were associated with DMARD treatment. RESULTS: A total of 426 patients were ≤1 year without DMARDs, 1090 > 1 year without DMARDs and 8773 (85%) currently had DMARD treatment. Of the patients who were without DMARDs for more than 1 year, 51% were in remission. Even if no remission criteria were met, the rheumatologists nevertheless found the strived for RA situation in the majority of patients. Of the patients who were without DMARDs for more than 1 year, 13% received glucocorticoid treatment >5 mg/day. In patients with a high degree of severity (odds ratio, OR severe vs. asymptomatic/mild 2.33, 95% confidence interval, CI 1.80;3.02) or positive rheumatoid factor (OR 2.24, CI 1.96;2.56) the chance of receiving DMARD treatment was twice as high. Existing comorbidities did not reduce the chance of receiving DMARD treatment. CONCLUSION: The RA patients in the national database who had no DMARDs for more than 1 year were mostly in remission or with low disease activity. Signs of inadequate disease control were found in only 11% of all patients without DMARD treatment.
33054324 Preclinical Evaluation of a Single Intravenous Infusion of hUC-MSC (BX-U001) in Rheumatoid 2020 Jan Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 10(6) cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.
33276135 Response to interleukin-6 receptor antagonists in patients with rheumatoid arthritis is in 2021 Jan OBJECTIVE: To investigate whether early response to tocilizumab (TCZ) and sarilumab (SAR) therapy in patients with active rheumatoid arthritis (RA) is influenced by previous use of biologic agents. METHODS: We performed a systematic literature review and a meta-analysis of original studies that analyzed the effectiveness of TCZ or SRL in subgroups of RA patients, including biologic-naïve patients versus those with inadequate response to at least one biologic DMARD (bDMARD), and patients with failure to 1 versus≥2 bDMARDs. RESULTS: The study selection process finally included 17 articles corresponding to 14 studies, including 7 randomized controlled trials (RCTs). Although the existing literature that compared the response in biologic-naïve patients versus those with inadequate response to at least one bDMARD showed conflicting results, meta-analysis of 6 published studies revealed a significantly higher likelihood of remission (RR=1.3; 95% CI: 1.2-1.5) and low activity disease (RR=1.3; 95% CI: 1.2-1.4) in the biologic-naïve group at week 24. However, differences between groups were not clinically meaningful in all studies and not always maintained after 6 to 12months of treatment. In addition, data from RCT RADIATE and TARGET suggest that the response to IL-6 pathway inhibitors seems to be similar, regardless of the number of tumor necrosis factor inhibitors (TNFis) previously tested. CONCLUSION: Disease activity was more rapidly reduced in the early stages of treatment in biologic-naïve patients. However, near similar efficacy can be expected in patients who experienced a failure of at least one bDMARD (mainly TNFis) beyond the first 6 to 12months of treatment, suggesting that the response occurs independently of the number of prior TNFis.