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ID PMID Title PublicationDate abstract
31366272 Elevated levels of inflammatory markers in women with rheumatoid arthritis. 2019 Rheumatoid arthritis (RA) is an autoimmune and progressive disease. Evidence indicates that inflammatory mediators may contribute to the genesis and/or evolution of this clinical condition. Thus, the objective was to evaluate and compare the plasma levels of Interleukin-17 (IL-17), Tumor Necrosis Factor-Alpha (TNF-α) and Complement 3 (C3) in women with RA and healthy controls (HC), as well as to evaluate the association them with the disease activity. 25 women with RA and 15 HC were recruited. Plasma levels of biomarkers were measured by ELISA. All statistical analyzes were performed with a significance level set at α = 0.05. In the women with RA, the median age was 55 and, in the HC, was 50 years. The median value of DAS-28 was 3.79. The plasma levels of IL-17 (p = .03), TNF-α (p ≤ 0.01) and C3 (p ≤ 0.01) were higher in women with RA. The ROC curve showed that TNF- α has a higher discriminating ability than IL-17 and C3. DAS-28 score correlated significantly with C3 levels in women with RA (r = 0.91; p < .01). These findings reaffirm the participation of the immune system in pathophysiology of RA, suggest that TNF-α levels may be a good biomarker and that elevated C3 levels contribute to the worsening of the disease.
31242568 Reduced Anti-Histone Antibodies and Increased Risk of Rheumatoid Arthritis Associated with 2019 Jun 25 Autoantibodies against citrullinated proteins are a hallmark of rheumatoid arthritis, a destructive inflammatory arthritis. Peptidylarginine deiminase 4 (PAD4) has been hypothesized to contribute to rheumatoid arthritis by citrullinating histones to induce neutrophil extracellular traps (NETs), which display citrullinated proteins that are targeted by autoantibodies to drive inflammation and arthritis. Consistent with this theory, PAD4-deficient mice have reduced NETs, autoantibodies, and arthritis. However, PAD4's role in human rheumatoid arthritis is less clear. Here, we determine if single nucleotide polymorphism rs2240335 in PADI4, whose G allele is associated with reduced PAD4 in neutrophils, correlates with NETs, anti-histone antibodies, and rheumatoid arthritis susceptibility in North Americans. Control and rheumatoid arthritis subjects, divided into anti-cyclic citrullinated peptide (CCP) antibody positive and negative groups, were genotyped at rs2240335. In homozygotes, in vitro NETosis was quantified in immunofluorescent images and circulating NET and anti-histone antibody levels by enzyme linked immunosorbent assay (ELISA). Results were compared by t-test and correlation of rheumatoid arthritis diagnosis with rs2240335 by Armitage trend test. NET levels did not significantly correlate with genotype. G allele homozygotes in the CCP(-) rheumatoid arthritis group had reduced anti-native and anti-citrullinated histone antibodies. However, the G allele conferred increased risk for rheumatoid arthritis diagnosis, suggesting a complex role for PAD4 in human rheumatoid arthritis.
30148435 Methotrexate did not improve endothelial function in rheumatoid arthritis: a study in rats 2019 Jan OBJECTIVES: Rheumatoid arthritis is associated with an increased cardiovascular risk, secondary to endothelial dysfunction. There is accumulating evidence that methotrexate reduces cardiovascular risk in rheumatoid arthritis, but the mechanisms involved are still unknown. In this study, we aimed to determine the effect of methotrexate on endothelial function and traditional cardiovascular risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS: On the first signs of arthritis, methotrexate (1 mg/kg/week, s.c.) or saline (Vehicle) was administered to AIA for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine in the presence or not of inhibitors of nitric oxide synthase, cyclooxygenase-2, arginase, EDHF and superoxide anions production. Arthritis and radiological scores, blood pressure and blood levels of cytokines, triglycerides, cholesterol, homocysteine and BMP-4 were measured. RESULTS: Although methotrexate significantly reduced the arthritis score, it had no effect on Ach-induced relaxation. As regards mechanisms, methotrexate increased nitric oxide synthase activity and reduced the superoxide anions production but did not change arginase, cyclooxygenase-2 and EDHF pathways. Methotrexate did not change the radiological score or blood pressure, lipid, glucose and homocysteine levels. By contrast, methotrexate significantly reduced plasma IL-1β and TNF-α levels and increased serum BMP-4 level. CONCLUSIONS: Despite a reduction of clinical and biological inflammation, methotrexate did not improve endothelial function in AIA rats. Overall data suggest that mechanisms other than the ED reduction are likely involved, and remain to be elucidated to better understand the cardiovascular benefits of methotrexate in rheumatoid arthritis.
30081197 Methotrexate mechanism in treatment of rheumatoid arthritis. 2019 May Methotrexate has been used in treatment of rheumatoid arthritis (RA) since the 1980s and to this day is often the first line medication for RA treatment. In this review, we examine multiple hypotheses to explain the mechanism of methotrexate efficacy in RA. These include folate antagonism, adenosine signaling, generation of reactive oxygen species (ROS), decrease in adhesion molecules, alteration of cytokine profiles, and polyamine inhibition amongst some others. Currently, adenosine signaling is probably the most widely accepted explanation for the methotrexate mechanism in RA given that methotrexate increases adenosine levels and on engagement of adenosine with its extracellular receptors an intracellular cascade is activated promoting an overall anti-inflammatory state. In addition to these hypotheses, we examine the mechanism of methotrexate in RA from the perspective of its adverse effects and consider some of the newer genetic markers of methotrexate efficacy and toxicity in RA. Lastly, we briefly discuss the mechanism of additive methotrexate in the setting of TNF-α inhibitor treatment of RA. Ultimately, finding a clear explanation for the pathway and mechanism leading to methotrexate efficacy in RA, there may be a way to formulate more potent therapies with fewer side effects.
31413865 Comparative effect of tumour necrosis factor inhibitors versus other biological agents on 2019 BACKGROUND: To comparatively investigate the differential effect of second-line tumour necrosis factor inhibitors (TNFis) versus other biological agents on cardiovascular disease (CVD) risk-associated biomarkers in patients with rheumatoid arthritis (RA). METHODS: We evaluated the serum levels of lipoprotein-associated apoproteins ApoA1 and ApoB100 and lipoprotein(a) (Lp(a)) and the leptin/adiponectin ratio (LAR) as an insulin resistance proxy in patients with RA from the Rotation Or Change (ROC) trial treated with either a second-line TNFi or another biologic (tocilizumab (TCZ), rituximab or abatacept) at baseline and week 24. We compared the changes in biomarker levels in each group and according to the EULAR response. RESULTS: Of the 300 patients enrolled in the ROC trial, 203 were included in the study, including 96 in the second-line TNFi group and 107 in the other biological group. The measured biomarkers did not deteriorate between baseline and week 24 regardless of the group. A greater improvement in the LAR was noted in the other biological group (median (IQR) -0.12 ng/µg (-0.58 to 0.31) vs 0.04 (-0.19 to 0.43), p=0.033), and a greater improvement in the Lp(a) level was observed following treatment with TCZ than with a TNFi (-0.05 g/L (-0.11 to -0.01) vs -0.01 g/L (-0.02 to 0.01), p<0.001). When considering the patients' responses to treatment, improved biomarkers were mainly observed in the EULAR responders in each treatment group. CONCLUSIONS: TNFis and non-TNFis were neutral on improved CVD risk-associated biomarkers in patients with RA insufficiently controlled by TNFis. TCZ could be associated with a better improvement concerning Lp(a) and LAR than TNFis. This improvement could be related to a good therapeutic response, thereby supporting the need of good control of RA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier NCT01000441, registered on 22 October 2009.
30724643 Distributive differences of P2Xs between the forelimb and hind limb of adjuvant arthritis 2019 Dec CONTEXT: Notopterygium incisum Ting ex H. T. Chang (Umbelliferae) (NI) specializes in treatment of upper limb rheumatoid arthritis (RA), but the exact mechanism is unclear. P2Xs are useful targets for inflammatory pain therapy. It led us to hypothesize that NI may preferentially act on particular P2Xs and these receptors may be unevenly distributed in the upper/lower limb. OBJECTIVE: To investigate P2Xs distribution in the upper/lower limb and NI's targets in upper limb RA. MATERIALS AND METHODS: The SD rats were randomized into 11 groups of 10 animals each. Eight experimental groups were established by the injection of 0.1 mL FCA into the plantar surface of rat paw. Three control groups suffered the same volume of saline. The articular cavities were then taken on the seventh day to detect P2Xs expression. NI (3 g/kg) and prednisone (10 mg/kg) were respectively given by oral gavage once daily for 14 d. The swelling degree and P2Xs were evaluated individually. RESULTS: In normal rats, the expressions of P2X(3) and P2X(6) in forelimb were markedly higher than that of in hind limb (P < 0.05). After induced by FCA, P2X(1), P2X(3), P2X(4), P2X(5) and P2X(7) were increased significantly (P < 0.01). The biggest difference was P2X(3). In NI treatment rats, swelling degree of the 7th/14th day in forelimb was 68.24%/38.89%, whereas that of in hind limb was 88.72%/79.92%. P2X(3) mRNA and protein expression was significantly reduced as contrasted with the control group (P < 0.05). CONCLUSIONS: P2X(3) receptor was predominantly expressed in the forelimb RA rat. NI relieved the FCA-induced RA by inhibiting upper limb's P2X(3) receptor.
30321979 The impact of hindfoot deformities for the recurrence of hallux valgus after joint-preserv 2019 Jun BACKGROUND: Recurrence of hallux valgus (HV) is a common complication after forefoot surgery for rheumatoid forefoot deformities. The aim of this study is to evaluate the impact of hindfoot malalignment on recurrence. METHODS: This was a retrospective observational study designed to analyze the radiographic outcomes of 87 feet in 64 patients with rheumatoid arthritis treated with a joint-preserving surgery for HV deformity. Differences in hindfoot alignment preoperatively between the recurrence and nonrecurrence groups was compared. RESULTS: There were no significant differences in hindfoot alignment preoperatively between groups. To estimate the impact of technical problems, the HV and intermetatarsal angles measured from radiographs 3 months postoperatively were compared between groups. The HV angles in the recurrence group were significantly larger than those in the nonrecurrence group (p=0.02). CONCLUSIONS: There were no significant differences between preoperative hindfoot malalignment and postoperative recurrence of HV in rheumatoid forefoot surgeries.
30442826 Fertility and Ovarian Reserve among Women with Rheumatoid Arthritis. 2019 May OBJECTIVE: We sought to identify causes for infertility in women with and without rheumatoid arthritis (RA). METHODS: Women with RA were matched to healthy controls. Differences in anti-Müllerian hormone (AMH) and anovulation were analyzed. RESULTS: Women with RA had lower AMH (β -1.05, 95% CI -2.09 to -0.005), but no difference was observed when AMH was log-transformed. No difference in anovulation was observed. Infertility prevalence was similar between groups, primarily attributable to polycystic ovary syndrome in healthy controls but largely unexplained in women with RA. CONCLUSION: AMH was lower in women with RA, but reasons for infertility among women with RA remain unknown.
29623847 Adenosine Deaminase Activity and HLA-DRB as Diagnostic Markers for Rheumatoid Arthritis. 2019 BACKGROUND: Rheumatoid Arthritis (RA) is a chronic multi systemic disorder with the unclarified ethiopathology. Although several markers have been presented for recognition of RA, but none of them has been specific. New markers such as HLA typing and activity of Adenosine Deaminase (ADA) isoenzymes could be useful and specific. OBJECTIVE: The aim of this study is to evaluate the pattern of ADA isoenzymes activity and HLA typing in both RA patients and healthy cases. METHODS: Blood samples were collected from 55 RA patients and 60 healthy subjects, over a period of 6 months. Levels of C-reactive Protein (CRP), Rheumatoid Factor (RF) and ADA (ADA1, ADA2, total ADA) were measured using AVITEX kit and HITACHI Auto Analyzer. In addition, HLA-DRB1*01,*04 and *10 was detected using PCR-SSP. RESULTS: ADA activity, particularly ADA2 level, was significantly higher among RA group (Pv <0.05). The concentrations of tADA in patients with RF and CRP positive were significantly higher (Pv <0.05). The allele prevalence of DRB1*01 was significantly higher in RA patients (13.1%) compared with control group (5.5%, respectively) (P <0.05, Bonferroni adjustment P<0.003). Calculated sensitivity and specificity for diagnostic tests in this study are listed as: CRP (75%), RF (80%), ADA (84%) and RF (90%), ADA (83%), CRP (72%), respectively. CONCLUSION: Increased tADA level and the frequency of DRB1*10 and *01 caused susceptibility to RA.
31747811 Coix lachryma-jobi extract ameliorates inflammation and oxidative stress in a complete Fre 2019 Dec Context: Adlay seed [Job's tears, Coix lachryma-jobi L. var. ma-yuen Stapf (Poaceae)] is a Traditional Chinese Medicine, which has been investigated to treat inflammatory diseases and rheumatism.Objective: This study evaluates the ameliorative effects of adlay seed extract (ASE) in a complete Freund's adjuvant (CFA)-induced rheumatoid arthritis (RA) rats.Materials and methods: The RA Sprague-Dawley rat model was induced and randomly divided into six groups with or without ASE treatment (50, 100 or 200 mg/kg). After 28 d administration, the symptoms, biochemical parameters and molecular mechanisms were investigated.Results: The values of paw oedema, PGE(2) and MMP-3 decreased from 1.46 ± 0.04 to 0.66 ± 0.07 cm(3), from 126.2 ± 11.48 to 79.71 ± 6.8 pg/mL and from 142.7 ± 8.36 to 86.51 ± 5.95 ng/mL, respectively; the values of body weight increased from 177.25 ± 5.94 to 205 ± 6.52 g in HASE group. In addition, treatment of ASE reduced the levels of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, MCP-1), and increased the activities of antioxidant enzyme (GSH-Px, SOD, and CAT). Furthermore, ASE could suppress the mRNA expression of COX-2 and CHI3L1 and improve the mRNA expression of CAT and GPx-1 in ankle tissues of RA rats.Discussion and conclusions: For the first time, our results indicated ASE exerts anti-RA effects via inhibiting pro-inflammatory factors and alleviating oxidative stress. Our finding sheds light on the research and development of anti-RA functional foods from adlay seed.
30733073 Increased Staphylococcus aureus Nasal Carriage Rates in Rheumatoid Arthritis Patients on B 2019 May BACKGROUND: Rheumatoid arthritis patients are at increased risk for periprosthetic joint infection after arthroplasty. The reason is multifactorial. Nasal colonization with Staphylococcus aureus is a modifiable risk factor; carriage rates in RA patients are unknown. The goal of this study is to determine the S aureus nasal carriage rates of RA patients on biologics, RA patients on traditional disease-modifying anti-rheumatic drugs (DMARDs), and osteoarthritis. METHODS: Consecutive patients with RA on biologics (±DMARDs), RA on non-biologic DMARDs, or OA were prospectively enrolled from April 2017 to May 2018. One hundred twenty-three patients were determined necessary per group to show a difference in carriage rates. Patients underwent a nasal swab and answered questions to identify additional risk factors. S aureus positive swabs were further categorized using spa typing. Logistic regression evaluated the association with S aureus colonization between the groups after controlling for known risk factors. RESULTS: RA patients on biologics, 70% of whom were on DMARDs, had statistically significant increase in S aureus colonization (37%) compared to RA on DMARDs alone (24%), or OA (20%) (P = .01 overall). After controlling for glucocorticoids, antibiotic use, recent hospitalization, and diabetes, RA on biologics had a significant increased risk of S aureus nasal colonization (Odds ratio 1.80, 95% confidence interval 1.00-3.22, P = .047). CONCLUSION: S aureus colonization risk was increased for RA on biologics compared to RA not on biologics and OA. Nasal S aureus carriage increases the risk of surgical site infection; this modifiable risk factor should be addressed prior to total joint arthroplasty for this higher risk patient group.
31068244 Relationships between Cytokine Levels and Disease Parameters during the Development of a C 2019 May 1 In rheumatoid arthritis research, NHP models of collagen-induced arthritis are important because these species share many immunologic and pathologic features with humans. In addition, serum levels of various cytokines in patients with rheumatoid arthritis have been studied as immune markers for disease prediction, early diagnosis, and effective therapeutic management. The purpose of this study was to identify changes in cytokine levels that occur during the development of collagen-induced arthritis in female cynomolgus macaques (n = 8) and to assess the relationships between these changes and various disease parameters. Blood samples were collected weekly before (week 0) and after (weeks 1 through 7) immunization with type II collagen; clinicopathologic and cytokine data from those samples and other clinical parameters were used in correlation analysis. Serum levels of IFN γ, chemokine (C-C motif) ligand 2 (CCL2), and IL6 showed significant changes after generation of collagen-induced arthritis. IFNγ levels showed a strong negative correlation with body weight (an indicator of general body condition), and CCL2 and IL6 showed moderate negative correlation with body weight. Serum IL6 levels showed moderate positive correlation with the soft tissue swelling score and strong positive correlation with serum C-reactive protein levels in our NHP model of collagen-induced arthritis. In addition, serum levels of matrix metalloproteinase 3 increased significantly after inoculation with type II collagen and showed a moderate positive correlation with serum levels of C-reactive protein, IL6, and IL15. These results suggest close correlations between various cytokines and disease parameters in NHP models of rheumatoid arthritis. These cytokines therefore potentially could be used as markers for monitoring the efficacy of novel treatments in NHP models of rheumatoid arthritis.
29644891 A survey of physiotherapists' current management and the promotion of physical activity, i 2019 Sep Purpose: Establishing physiotherapists' management of people with rheumatoid arthritis, in addition to their promotion of physical activity, is important to ascertain if there are educational needs in this area. Materials and methods: Physiotherapists from three Irish Chartered Physiotherapy clinical interest groups (N = 457) were invited to participate in a cross-sectional online questionnaire hosted on SurveyMonkey((R))™. Results: One hundred and sixty-eight (168/457; 37%) responded. Exercise prescription and education were the most frequent treatments, with 84% always/regularly providing same. Physical activity is a component of treatment with 52% always/regularly advising. In addition, 69% agree that physical activity is attainable, 68% safe, and 67% an important goal. However, 62% never recommend the appropriate guidelines, while 14% define physical activity according to frequently used definitions. There was a statistically significant association between longer years qualified and more years working with people with RA, when using guidelines to guide physical activity and exercise prescription. Low-intensity exercises were prescribed by however, 67% never provide high-intensity. Conclusions: Current practice is in line with guidelines in which, exercise therapy and education are considered as the mainstay. Promotion of physical activity is strong; however, two-thirds never recommend the appropriate guidelines, and only a minority defined physical activity correctly. The majority never prescribe high-intensity exercise. There is a need to develop education and training for physiotherapists in the promotion of physical activity in people with rheumatoid arthritis. Implications for rehabilitation Exercise therapy and education are considered as the mainstay in the physiotherapy management of people with rheumatoid arthritis. Those physiotherapists' who are qualified longer and have more experience working with people with rheumatoid arthritis use the relevant physical activity guidelines. Overall there is a need to develop education and training for physiotherapists in the promotion of physical activity in people with rheumatoid arthritis.
31541358 Pharmacological Management of Osteoporosis in Rheumatoid Arthritis Patients: A Review of t 2019 Dec Rheumatoid arthritis (RA) is a chronic disabling disease that is associated with increased localized and generalized osteoporosis (OP). Previous studies estimated that approximately one-third of the RA population experience bone loss. Moreover, RA patients suffer from a doubled fracture incidence depending on several clinical factors, such as disease severity, age, glucocorticoid (GC) use, and immobility. As OP fractures are related to impaired quality of life and increased mortality rates, OP has an enormous impact on global health status. Therefore, there is an urgent need for a holistic approach in daily clinical practice. In other words, both OP- and RA-related factors should be taken into account in treatment guidelines for OP in RA. First, to determine the actual fracture risk, dual-energy X-ray absorptiometry (DXA), including vertebral fracture assessment (VFA) and calculation of the 10-year fracture risk with FRAX(®), should be performed. In case of high fracture risk, calcium and vitamin D should be supplemented alongside anti-osteoporotic treatment. Importantly, RA treatment should be optimal, aiming at low disease activity or remission. Moreover, GC treatment should be at the lowest possible dose. In this way, good fracture risk management will lead to fracture risk reduction in RA patients. This review provides a practical guide for clinicians regarding pharmacological treatment options in RA patients with OP, taking into account both osteoporotic-related factors and factors related to RA.
29998825 Rapid immunoprofiling of cytokines, chemokines and growth factors in patients with active 2019 Jan OBJECTIVES: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease of unknown etiology, characterised by symmetric erosive synovitis, leading inevitably to the destruction of cartilage and bone as well as bursa and tendon sheaths of joints. Our aim of this study was to decipher the differential expression of cytokines, chemokines and growth factors in the plasma of RA patients with active disease, using magnetic bead-based Luminex Multiple Analyte Profiling (xMAP) technology, for precision medicine. METHODS: We obtained plasma samples from RA patients (n=25) from the Rheumatology Clinic at the King Abdulaziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) after written informed consent for their inclusion in this study. Besides, we have used the plasma samples from inflammatory osteoarthritis (OA) patients (n=10) and healthy volunteers (n=10) for comparison analyses. Plasma samples were examined using the Human Cytokine Magnetic 30-plex panel (Novex®), Invitrogen, USA) and analysed by MAGPIX® instrument (Luminex Corporation, USA). RESULTS: Though several pro-inflammatory cytokines, chemokines and growth factors present in the 30plex magnetic bead panel were not significantly (p>0.05) increased in the plasma of RA patients, the levels of plasma Th1 associated proinflammatory cytokines TNFα, and IL-6 and Th2 associated cytokines such as IL-4, IL-5 and IL-13 were significantly (p<0.05) upregulated compared to OA and normal controls. The proinflammatory IL-12 as well as anti-inflammatory IL-10 and IL-1RA were significantly (p<0.05) upregulated in the plasma of RA patients compared to normal controls. Also, the chemokines such as IP-10, RANTES and IL-8 as well as growth factors such as EGF, and VEGF were significantly (p<0.05) increased in RA. CONCLUSIONS: The MAGPIX data showed that the cytokines, chemokines and growth factors were differentially regulated systemically in patients with active RA compared to OA and normal controls. Hence, the Luminex xMAP technology-based multiplex immunoassays offer clues to formulate effective therapeutic strategies for RA patients with active disease irrespective of their treatment regimen and duration of treatment and, thus, an indispensable tool in precision medicine.
31590930 Differences in disease activity measures in patients with rheumatoid arthritis who achieve 2020 Apr OBJECTIVES: In patients with rheumatoid arthritis (RA), remission may be assessed by various composite measures. We assessed achievement of remission as defined by Boolean criteria, Simplified Disease Activity Index (SDAI), Clinical Disease Activity Index (CDAI), and 28-joint Disease Activity Score using C-reactive protein (DAS28[CRP]) and determined the components that limit patients in SDAI, CDAI, or DAS28(CRP) remission from achieving Boolean remission. METHODS: The proportions of patients achieving Boolean, SDAI, CDAI, or DAS28(CRP) remission were calculated for 3 trials: PREMIER and OPTIMA in patients with early RA and DE019 in patients with established RA. At the first visit that remission was recorded during the first 52 weeks of the trial, the following were assessed: swollen/tender joint count at 28 and 66/68 joints, CRP, Patient's/Physician's Global Assessment (PGA/PhGA), SDAI, DAS28(CRP), and Health Assessment Questionnaire-Disability Index. RESULTS: The majority of patients (61-66%) who achieved SDAI or CDAI remission also attained Boolean remission. Although DAS28(CRP) remission was most frequently attained, 74-77% of patients in DAS28(CRP) remission did not achieve Boolean remission. Compared with patients in Boolean remission, patients in SDAI or CDAI remission but not Boolean remission had higher PGA scores, while patients with DAS28(CRP) remission but not Boolean remission had higher joint counts, and PGA and PhGA scores. CONCLUSIONS: Differences in PGA limit patients in SDAI/CDAI remission from meeting the Boolean remission criteria, suggesting that these criteria otherwise can be used interchangeably. In contrast, patients in DAS28(CRP) remission are limited by differences in multiple disease activity measures from achieving Boolean remission.
31376263 Imaging in the preclinical phases of rheumatoid arthritis. 2020 May There is growing evidence that the development of rheumatoid arthritis (RA) is a multistep process. The European League Against Rheumatism (EULAR) identified different phases before the onset of RA, from the presence of genetic and environmental risk factors for RA, towards clinically suspected arthralgia and undifferentiated arthritis. Currently, a new definition of "window of opportunity" is emerging; this states that the window could even lie in preclinical phase of RA, preceding diagnosis or fulfillment of classification criteria for RA. In this scenario, the detection of subclinical inflammation by imaging tools could be useful together with autoantibodies and joint symptoms to better stratify people at high risk for developing RA and to plan prevention trials in high-risk cohorts. This review will give an overview on the use of computed tomography, magnetic resonance imaging and ultrasonography in the preclinical phases of RA.
31678927 Mania induced by isoniazid preventive therapy during steroid treatment for rheumatoid arth 2019 Nov 2 Isoniazid preventative therapy is widely used for latent tuberculosis infection. Isoniazid is highly effective but has many adverse effects, including neuropsychiatric. We describe the case of an 80-year-old woman with mania. She had received isoniazid preventative therapy during steroid treatment for rheumatoid arthritis and organising pneumonia for the previous 5 months. Her mania resolved after discontinuation of isoniazid. Adverse effects of isoniazid should be considered even if a long time has elapsed since the start of administration. Physicians other than infectious disease and respiratory specialists also must be aware of the adverse effects of isoniazid preventative therapy.
31478999 Glial Fibrillary Acidic Protein (GFAP) Autoimmunity in the Setting of Seropositive Rheumat 2019 Sep INTRODUCTION: Glial fibrillary acidic protein (GFAP) immunoglobulin G is a recently discovered biomarker of an autoimmune central nervous system disorder characterized by a steroid-responsive meningoencephalomyelitis. CASE REPORT: A 63-year-old man with rheumatoid arthritis on etanercept presented with steroid-responsive subacute encephalopathy and foot drop. Brain and sural nerve biopsies demonstrated a T-cell perivascular infiltrate. Cerebrospinal fluid studies 18 months into the course of the illness demonstrated a GFAP antibody on mouse tissue immunofluorescence confirmed by cell-based assay. The patient was treated with steroids and cyclophosphamide leading to resolution of his symptoms. CONCLUSION: This case expands on the previously reported cases of GFAP immunoglobulin G autoimmunity by describing an associated inflammatory large fiber peripheral neuropathy.
30714583 Distribution of abnormal IgG glycosylation patterns from rheumatoid arthritis and osteoart 2019 Mar 11 Glycosylation is a post-translational modification essential for maintaining the structure and function of proteins. Abnormal N-glycan patterns have been found in various diseases compared to healthy controls. A decrease in terminal galactosylated N-glycans of serum IgG in rheumatoid arthritis (RA) and osteoarthritis (OA) may be involved in their immunopathogenesis. However, how glycan patterns differ between RA and OA remains unclear. Here, we identified 15 glycan forms of serum IgG from RA and OA using MALDI-TOF MS. We found that IgG galactosylation represented a suitable candidate for differentiating RA from healthy controls (AUC > 0.9). Then, we performed binary logistic regression to screen out three bisecting N-acetylglucosamine (GlcNAc) glycoforms for distinguishing between OA and RA. Combined ROC analysis of the selected glycans yielded an AUC of 0.81 between OA and RA and an AUC of 0.79 between OA and RF/ACPA negative RA. Similar results were found in the validation set. In conclusion, our analysis demonstrates that RA and OA are distinguished on the basis of their different IgG glycan patterns, which thus serve as suitable candidates as biomarkers for reliably identifying clinical conditions such as RA and OA.