Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
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| 34112656 | Comparison of two dose escalation strategies of methotrexate in active rheumatoid arthriti | 2021 Nov | OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549. | |
| 33999267 | [Quality in acute inpatient rheumatology 2021 : Current aspects of the KOBRA quality label | 2021 Oct | A comprehensive health policy quality campaign launched in 2021 aims to improve the quality and transparency of hospital care for people with diseases in Germany. Legal requirements for minimum volumes and the expansion of quality contracts between cost units and hospitals as well as the use of quality indicators relevant to planning for demand-oriented and quality-oriented further development of inpatient care will increase competition in the quality of care between hospitals. The topic of development and definition of quality in medicine was also comprehensively addressed by the Association of Rheumatological Acute Care Clinics (VRA) shortly after its foundation in 1998. At the center of acute inpatient quality management are binding structural criteria linked to the continuous outcome benchmarking in acute rheumatology care (KOBRA) project launched in 2003 in rheumatology (and continuously implemented to date) measuring process and outcome quality. Based on this framework (fulfillment of the structural quality and participation in the KOBRA project) successfully participating rheumatology units can acquire the KOBRA seal of approval for 2 years at a time, which is awarded by the project management, the aQua Institute. The outstanding position of the project is exemplified by data evaluation on treatment change in active rheumatoid arthritis, diagnosis confirmation of connective tissue diseases and vasculitis during the inpatient stay as well as on participatory decision-making processes concerning rheumatoid arthritis (referring to the results of the data collection period 2018). By anchoring projects for structural, process and outcome quality acute inpatient rheumatology is well prepared for the paradigm shift demanded by health policies. Additionally, the KOBRA project is a good prerequisite to meet the requirements concerning quality management fixed in the Federal Joint Committee (G-BA) guidelines for recognition as a rheumatology center. | |
| 34715926 | Sustained microglial activation in the area postrema of collagen-induced arthritis mice. | 2021 Oct 29 | BACKGROUND: Central nervous system (CNS)-mediated symptoms, such as fatigue, depression, and hyperalgesia, are common complications among patients with rheumatoid arthritis (RA). However, it remains unclear how the peripheral pathology of RA spreads to the brain. Accumulated evidence showing an association between serum cytokine levels and aberrant CNS function suggests that humoral factors participate in this mechanism. In contrast to the well-known early responses of microglia (CNS-resident immune cells) in the area postrema [AP; a brain region lacking a blood-brain barrier (BBB)] to experimental inflammation, microglial alterations in the AP during chronic inflammation like RA remain unclear. Therefore, to determine whether microglia in the AP can react to persistent autoimmune-arthritis conditions, we analyzed these cells in a mouse model of collagen-induced arthritis (CIA). METHODS: Microglial number and morphology were analyzed in the AP of CIA and control mice (administered Freund's adjuvant or saline). Immunostaining for ionized calcium-binding adaptor molecule-1 was performed at various disease phases: "pre-onset" [post-immunization day (PID) 21], "establishment" (PID 35), and "chronic" (PID 56 and 84). Quantitative analyses of microglial number and morphology were performed, with principal component analysis used to classify microglia. Interleukin-1β (IL-1β) mRNA expression was analyzed by multiple fluorescent in situ hybridization and real-time polymerase chain reaction. Behavioral changes were assessed by sucrose preference test. RESULTS: Microglia in the AP significantly increased in density and exhibited changes in morphology during the establishment and chronic phases, but not the pre-onset phase. Non-subjective clustering classification of cell morphology (CIA, 1,256 cells; saline, 852 cells) showed that the proportion of highly activated microglia increased in the CIA group during establishment and chronic phases. Moreover, the density of IL-1β-positive microglia, a hallmark of functional activation, was increased in the AP. Sucrose preferences in CIA mice negatively correlated with IL-1β expression in brain regions containing the AP. CONCLUSIONS: Our findings demonstrate that microglia in the AP can sustain their activated state during persistent autoimmune arthritis, which suggests that chronic inflammation, such as RA, may affect microglia in brain regions lacking a BBB and have various neural consequences. | |
| 34126437 | Comparison of frailty associated factors between older adult patients with rheumatoid arth | 2021 Sep | PURPOSE: To determine whether frailty associated factors differ between community dwellers and older adult patients with rheumatoid arthritis (RA). METHODS: We used the cross-sectional data for patients with RA from the RA epidemiological quality-of-life study (n = 210, mean age 71.8 ± 3.7 years) and community dwellers from the Japan Gerontological Evaluation Study (n = 53,255, mean age 71.7 ± 4.0 years). Frailty status was assessed using the Kihon Checklist (KCL), and the primary outcome was frailty (KCL score ≥8 points). Information on predictor variables, including age, sex, marital status, educational level, body mass index (BMI), drinking and smoking status and social participation were obtained from a standardized questionnaire. We employed Poisson regression to calculate the prevalence ratio (PR) of frailty according to its predictors. RESULTS: We found frailty in 37.6% of the patients with RA and 15.7% of the community dwellers. In the multivariate models, BMI and social participation were independently associated with frailty in patients with RA (BMI <18.5: PR, 1.62; 95% confidence interval [CI] 1.09-2.41. BMI ≥25.0: PR, 1.81; 95% CI 1.20-2.71. Active social participation: PR, 0.61; 95% CI 0.42-0.87) and community dwellers (BMI <18.5: PR, 1.77; 95% CI 1.67-1.88. BMI ≥25.0: PR, 1.27; 95% CI 1.22-1.33. Active social participation: PR, 0.46; 95% CI 0.44-0.48). All other predictors were significantly associated with frailty in the community dwellers. CONCLUSION: Maintaining appropriate body weight and participating in social activities are important for preventing frailty in patients with RA as well as community dwellers. | |
| 33892739 | Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular | 2021 Apr 23 | BACKGROUND: New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients. METHODS: We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy. RESULTS: Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy. CONCLUSION: Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment. | |
| 34669487 | Guided therapy selection in rheumatoid arthritis using a molecular signature response clas | 2021 Dec | BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose. | |
| 34039871 | A double-blind, double-dummy, randomized controlled, multicenter trial of 99Tc-methylene d | 2021 May 19 | BACKGROUND: Clinical observational studies revealed that 99Tc-methylene diphosphonate (99Tc-MDP) could reduce joint pain and swollenness in rheumatoid arthritis (RA) patients. This multicenter, randomized, double-blind, double-dummy study aimed to evaluate the effects of 99Tc-MDP plus methotrexate (MTX) vs. MTX alone or 99Tc-MDP alone on disease activity and structural damage in MTX-naïve Chinese patients with moderate to severe RA. METHODS: Eligible patients with moderate to severely active RA were randomized to receive 99Tc-MDP plus MTX (n = 59) vs. MTX (n = 59) alone or 99Tc-MDP (n = 59) alone for 48 weeks from six study sites across four provinces in China. The primary outcomes were the American College of Rheumatology 20% improvement (ACR20) response rates at week 24 and changes in modified total Sharp score at week 48. RESULTS: At week 24, the proportion of participants achieving ACR20 was significantly higher in the MTX + 99Tc-MDP combination group (69.5%) than that in the MTX group (50.8%) or 99Tc-MDP group (47.5%) (P = 0.03 for MTX + 99Tc-MDP vs. MTX, and MTX + 99Tc-MDP vs.99Tc-MDP, respectively). The participants in the MTX + 99Tc-MDP group and the 99Tc-MDP group had significantly less important radiographic progression than the participants in the MTX group over the 48 weeks (MTX + 99Tc-MDP vs. MTX: P = 0.03, 99Tc-MDP vs. MTX: P = 0.03, respectively). There was no significant difference in terms of adverse events (AEs) among the groups. No serious AEs were observed. CONCLUSIONS: This study demonstrated that the combination of 99Tc-MDP with MTX inhibited structural damage and improved disease activity in RA patients compared with MTX and 99Tc-MDP monotherapies, without increasing the rate of AEs. Additional clinical studies of 99Tc-MDP therapy in patients with RA are warranted. TRIAL REGISTRATION: Chictr.org, ChiCTR-IPR-14005684; http://www.chictr.org.cn/showproj.aspx?proj=10088. | |
| 33858976 | Effects of Denosumab in Japanese Patients With Rheumatoid Arthritis Treated With Conventio | 2021 Nov | OBJECTIVE: To evaluate the safety and efficacy of long-term denosumab 60 mg every 6 months (Q6M) or every 3 months (Q3M) in patients with rheumatoid arthritis (RA). METHODS: This 12-month, randomized, double-blind, placebo-controlled, multicenter, phase III trial with an open-label extension period from 12 to 36 months (DESIRABLE) enrolled Japanese patients with RA treated with placebo (P) for 12 months followed by either denosumab Q6M (P/Q6M) or denosumab Q3M (P/Q3M) for 24 months; denosumab Q6M for 36 months (Q6M/Q6M); or denosumab Q3M for 36 months (Q3M/Q3M). Efficacy was assessed by van der Heijde modified total Sharp score (mTSS), bone erosion score (BES), and joint space narrowing (JSN) score. RESULTS: Long-term treatment better maintained mTSS and BES suppression in the P/Q3M and Q3M/Q3M vs P/Q6M and Q6M/Q6M groups; changes from baseline in total mTSS (standard error) at 36 months were 2.8 (0.4) and 1.7 (0.3) vs 3.0 (0.4) and 2.4 (0.3), respectively, and corresponding changes in BES were 1.3 (0.2) and 0.4 (0.2) vs 1.4 (0.2) and 1.1 (0.2), respectively. No JSN effect was observed. Bone mineral density consistently increased in all groups after denosumab initiation, regardless of concomitant glucocorticoid administration. Serum C-terminal telopeptide of type I collagen decreased rapidly at 1 month postdenosumab administration (in both the initial 12-month [Q3M and Q6M groups] and long-term treatment [P/Q3M and P/Q6M groups] phases). Adverse event incidence leading to study drug discontinuation was similar across treatment groups. CONCLUSION: Denosumab treatment maintained inhibition of progression of joint destruction up to 36 months. Based on effects on BES progression, higher dosing frequency at an earlier treatment stage may be needed to optimize treatment. Denosumab was generally well tolerated. (ClinicalTrials.gov: NCT01973569). | |
| 34003970 | A systematic review and network meta-analysis of the safety of early interventional treatm | 2021 Oct 2 | OBJECTIVES: To evaluate the safety of treatment strategies in patients with early RA. METHODS: Systematic searches of MEDLINE, EMBASE and PubMed were conducted up to September 2020. Double-blind randomized controlled trials (RCTs) of licensed treatments conducted on completely naïve or MTX-naïve RA patients were included. Long-term extension studies, post-hoc and pooled analyses and RCTs with no comparator arm were excluded. Serious adverse events, serious infections and non-serious adverse events were extracted from all RCTs, and event rates in intervention and comparator arms were compared using meta-analysis and network meta-analysis (NMA). RESULTS: From an initial search of 3423 studies, 20 were included, involving 9202 patients. From the meta-analysis, the pooled incidence rates per 1000 patient-years for serious adverse events were 69.8 (95% CI: 64.9, 74.8), serious infections 18.9 (95% CI: 16.2, 21.6) and non-serious adverse events 1048.2 (95% CI: 1027.5, 1068.9). NMA showed that serious adverse event rates were higher with biologic monotherapy than with MTX monotherapy, rate ratio 1.39 (95% CI: 1.12, 1.73). Biologic monotherapy rates were higher than those for MTX and steroid therapy, rate ratio 3.22 (95% CI: 1.47, 7.07). Biologic monotherapy had a higher adverse event rate than biologic combination therapy, rate ratio 1.26 (95% CI: 1.02, 1.54). NMA showed no significant difference between strategies with respect to serious infections and non-serious adverse events rates. CONCLUSION: The study revealed the different risk profiles for various early RA treatment strategies. Observed differences were overall small, and in contrast to the findings of established RA studies, steroid-based regimens did not emerge as more harmful. | |
| 33897688 | Kynurenic Acid Analog Attenuates the Production of Tumor Necrosis Factor-α, Calgranulins | 2021 | Objectives: Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease with complex pathogenesis involving a variety of immunological events. Recently, it has been suggested that kynurenic acid (KYNA) might be a potential regulator of inflammatory processes in arthritis. KYNA has a definitive anti-inflammatory and immunosuppressive function. The aim of the present study is to investigate the complex effects of a newly synthesized KYNA analog-SZR72 on the in vitro production of tumor necrosis factor-α (TNF-α), tumor necrosis factor-stimulated gene-6 (TSG-6), calprotectin (SA1008/9), SA100 12 (EN-RAGE), and HNP1-3 (defensin-α) in the peripheral blood of patients with RA and the various effects of the disease. Methods: Patients with RA (n = 93) were selected based on the DAS28 score, medication, and their rheumatoid factor (RF) status, respectively. Peripheral blood samples from 93 patients with RA and 50 controls were obtained, and activated by heat-inactivated S. aureus. Parallel samples were pretreated before the activation with the KYNA analog N-(2-N, N-dimethylaminoethyl)-4-oxo-1H-quinoline-2-carboxamide hydrochloride. Following the incubation period (18 h), the supernatants were tested for TNF-α, TSG-6, calprotectin, S100A12, and HNP1-3 content by ELISA. Results: SZR72 inhibited the production of the following inflammatory mediators: TNF-α, calprotectin, S100A12, and HNP1-3 in whole blood cultures. This effect was observed in each group of patients in various phases of the disease. The basic (control) levels of these mediators were higher in the blood of patients than in healthy donors. In contrast, lower TSG-6 levels were detected in patients with RA compared to healthy controls. In addition, the KYNA analog exerted a stimulatory effect on the TSG-6 production ex vivo in human whole blood cultures of patients with RA in various phases of the disease. Conclusion: These data further support the immunomodulatory role of KYNA in RA resulting in anti-inflammatory effects and draw the attention to the importance of the synthesis of the KYNA analog, which might have a future therapeutic potential. | |
| 33559564 | Treatment of Proximal Ulnar Stump after Darrach or Sauvé-Kapandji Procedure by Transfer o | 2021 Mar | Background: Treatment of the proximal ulnar stump with the Darrach or Sauvé-Kapandji (SK) procedure remains controversial. Ulnar wrist symptoms can result, and although many surgeons attribute these to ulnar stump instability, they can also be caused by radioulnar convergence or stump irritation. We present a novel surgical method for protecting the proximal ulnar stump and avoiding these complications. Methods: Our cases were five men and five women (mean age 72.0 years, range, 34-89). Mean follow-up duration was 41.7 months (range, 6-101 months). Radiological findings were osteoarthritis in five, rheumatoid arthritis of distal radioulnar joint in three, and ulnocarpal abutment syndrome in two. Pronator quadratus (PQ) was released from its insertion on the radius and transferred dorsally to cover the proximal ulnar stump. Postoperative ulnar wrist symptoms such as ulnar stump tenderness, forearm range of motion, and grip strength were compared with contralateral values. Dynamic radioulnar impingement was evaluated by Lee and Scheker's stress roentgenogram. Nine patients completed the Patient Rated Wrist Evaluation (PRWE) at final follow-up. Results: No patients reported ulnar wrist pain or tenderness at the proximal ulnar stump. Postoperative forearm range of motion recovered almost to contralateral values in cases without preoperative forearm contracture. In the two cases with contracture, postoperative pronation and supination recovered to more than their preoperative range. Grip strength averaged 86.4% (range, 66.7-103%) of the contralateral value at final follow-up. Lees and Scheker's stress roentgenogram revealed marked radioulnar impingement in one case, mild impingement in four cases and none in five, yet no patient complained of pain during the maneuver. The mean PRWE score was 34.7 points (range, 0-52.5 points). Conclusions: Insertion-released PQ pedicle transfer is an effective treatment option for the proximal ulnar stump after the Darrach or SK procedure. | |
| 34378309 | Activation of formyl peptide receptor 1 elicits therapeutic effects against collagen-induc | 2021 Sep | Rheumatoid arthritis (RA) is an autoimmune disorder which shows production of autoantibodies, inflammation, bone erosion, swelling and pain in joints. In this study, we examined the effects of an immune-modulating peptide, WKYMVm, that is an agonist for formyl peptide receptors (FPRs). Administration of WKYMVm into collagen-induced arthritis (CIA) mice, an animal model for RA, attenuated paw thickness, clinical scores, production of type II collagen-specific antibodies and inflammatory cytokines. WKYMVm treatment also decreased the numbers of T(H) 1 and T(H) 17 cells in the spleens of CIA mice. WKYMVm attenuated T(H) 1 and T(H) 17 differentiation in a dendritic cell (DC)-dependent manner. WKYMVm-induced beneficial effects against CIA and WKYMVm-attenuated T(H) 1 and T(H) 17 differentiation were reversed by cyclosporin H but not by WRW4, indicating a crucial role of FPR1. We also found that WKYMVm augmented IL-10 production from lipopolysaccharide-stimulated DCs and WKYMVm failed to suppress T(H) 1 and T(H) 17 differentiation in the presence of anti-IL-10 antibody. The therapeutic administration of WKYMVm also elicited beneficial outcome against CIA. Collectively, we demonstrate that WKYMVm stimulation of FPR1 in DCs suppresses the generation of T(H) 1 and T(H) 17 cells via IL-10 production, providing novel insight into the function of FPR1 in regulating CIA pathogenesis. | |
| 33827581 | Helicobacter canis bacteraemia in a rheumatoid arthritis patient treated with tofacitinib: | 2021 Apr 8 | BACKGROUND: Non-Helicobacter pylori species (NHPS) are newly emerging bacteria that naturally inhabit birds and mammals apart from humans and rarely cause diseases in humans. In recent years, a rise in the number of cases associated with NHPS infections in humans has been observed. Among them, infections with Helicobacter (H.) canis are sporadic and challenging to recognise clinically. To date, ten cases of H. canis infections in mainly immunocompromised humans have been reported in the literature. Transmission pathway is most likely zoonotic via the faecal-oral route during close contacts with dogs and cats or may result from a contaminated sheep milk intake. No clear guidelines for successful antibiotic regimen are known. Important additional risk factor for infection might be biologic agents and Janus kinase inhibitors (JAKi) used in the treatment of rheumatoid arthritis (RA) and other conditions. Herein we present the first case of H. canis bacteraemia in a RA patient treated with novel JAKi tofacitinib. CASE PRESENTATION: A 65-year-old female patient with RA and rituximab-induced hypogammaglobulinemia treated with tofacitinib, methotrexate, and methylprednisolone came to a planned visit in our outpatient rheumatology clinic. She presented with a history of back pain that significantly worsened 2 days before visit. She had numbness and tingling sensation in both legs and muscle weakness. Neurological examination was within a normal range. The patient was afebrile, had no chills, and was haemodynamically stable. She was in close contact with her pet dogs. Laboratory examination showed increased markers of inflammation. She was found to have H. canis bacteraemia with underlying multilevel degenerative lumbar spinal stenosis. Identification of H. canis was performed by MALDI-TOF MS and 16Â S rRNA gene sequence analysis of isolate from subcultured positive aerobic blood culture bottles. Antimicrobial susceptibility testing showed low minimum inhibitory concentrations to amoxicillin-clavulanate, cefotaxime, ceftriaxone, meropenem, and gentamicin. She was treated with combined antibiotic regimen (ceftriaxone, doxycycline) for 14 days, which resulted in total remission of the infection. CONCLUSIONS: Clinicians should recognise H. canis infection risk in patients with recent pet exposure and predisposing factors such as immunodeficiency disorders or diseases that demand immunosuppressive drug therapy. A minimum of two weeks of antibiotic therapy is suggested. | |
| 33688303 | Dysregulation of Innate Lymphoid Cells in Patients with Active Rheumatoid Arthritis and Mi | 2021 | Innate lymphoid cells (ILCs) have roles in many diseases and immune pathways. To determine the roles of these cells in patients with rheumatoid arthritis (RA) and mice with collagen-induced arthritis (CIA), we measured ILC subsets using flow cytometry and multiplex immunofluorescence staining. Patients with stable RA had greater proportions of ILC2s and decreased proportions of ILC1s and ILC3s (all p < 0.05). The 28-joint disease activity (DAS28) score had positive correlations with the proportion of ILC1s and negative correlations with ILC2s (both p < 0.05). ILC2s of patients with RA expressed more IL-4 than healthy controls (p < 0.05). The proportions of ILC1s and ILC2s were greater in mice with CIA (both p < 0.05), especially the ILC2s in mice without arthritis after immunization and had correlations with multiple inflammatory and anti-inflammatory cytokines. Multiplex immunofluorescence staining described the distribution of ILCs in spleen tissues. Our results indicate that dysregulation of ILCs occurs during the pathogenesis of RA and CIA. | |
| 34238428 | [Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report o | 2021 Jun 30 | A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL. | |
| 34244838 | Degenerations in Global Morphometry of Cancellous Bone in Rheumatoid Arthritis, Osteoarthr | 2022 Jan | We have recently revealed significant differences in microarchitectural properties (i.e. global and local morphometries) and mechanical properties between rheumatoid arthritis (RA), osteoarthritis (OA) and osteoporosis (OP) in cancellous bones. This study compared these properties with those of ageing controls by matching bone volume fraction (BV/TV), the most important determinant for bones' mechanical properties, to investigate whether these bones have similar properties and degenerative potentials. RA, OA and OP femoral heads were harvested from patients undergoing total hip replacement surgery. The selected patients were matched by similar cancellous bone BV/TV, with seven patients in each group. Four samples were prepared from each femoral head and scanned with micro-CT to quantify microarchitectural properties and compression tested to determine mechanical properties. In terms of global morphometry, no significant differences were observed between these diseased bones. In terms of local morphometry, the number of plates in the RA group was significantly greater than that of the OP and control groups. Plate volume density in the RA group was significantly greater than in the control group. Interestingly, the ultimate stresses in the three diseased groups were 77% to 195% lower than in the control group (p < 0.001). Degenerations of global morphometry of cancellous bones in these diseased femoral heads are similar but more severe than in ageing controls matched by BV/TV, as evidenced by pronounced reduction in bone strength. This phenomenon suggests that some local morphometric parameters, along with other factors, such as abnormal collagen, mineralisation, erosion and microdamage, may contribute to further compromising mechanical properties. | |
| 33504421 | [Reduction of follicular regulatory T cells is associated with occurrence and development | 2021 Feb | Objective To investigate the potential mechanism of follicular regulatory T (Tfr) cells in the pathogenesis of rheumatoid arthritis (RA). Methods The percentage of CD4(+)CXCR5(+)FOXP3(+)ICOS(+) Tfr cells in the peripheral blood of 20 patients with RA and 20 healthy subjects were detected by flow cytometry, and the correlation between the proportion of Tfr cells and the clinical laboratory index of RA was analyzed. The serum levels of interleukin-10 (IL-10), IL-12, IL-2, transforming growth factor-β (TGF-β) and C-X-C motif chemokine ligand 13 (CXCL13) were measured by ELISA. The mRNA expression of Bcl6 and B lymphocyte induced mature protein 1 (Blimp-1) in peripheral blood mononuclear cells (PBMCs) was detected by real-time quantitative PCR. Immunohistochemistry was used to detect the expression of Bcl6 and CXCL13 in synovium of RA patients. Results The percentage of Tfr cells in the RA patients significantly decreased compared with the healthy controls, which was negatively related to the C reactive protein (CRP), rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), disease activity score in 28 joints (DAS28). The serum levels of IL-12 and CXCL13 in the patients with RA went up obviously, while the levels of IL-2, IL-10 and TGF-β went down remarkably. The Bcl6 mRNA level in PBMCs of the RA patients was significantly raised, while the expression of Blimp-1 mRNA was significantly reduced. Bcl6 and CXCL13 were highly expressed in the synovium of the RA patients. Conclusion The decrease of the proportion of Tfr cells in the peripheral blood may be related to the occurrence and development of RA. | |
| 33853479 | Proportion of T follicular helper cells in peripheral blood of rheumatoid arthritis patien | 2021 Jun | Introduction:Alterations in the levels and activity of Tfh may lead to impaired immune tolerance and autoimmune diseases. The aim of this study was to investigate the proportion and types of Tfh cells in the peripheral blood (PB) of RA patients.Areas covered:Comprehensive databases were searched for studies evaluating the proportion of Tfh cells in the PB of patients with RA compared to healthy control (HCs).The proportion of Tfh cells in RA patients was significantly higher than in HCs (SMD 0.699, [0.513, 0.884], p <Â 0.0001). Furthermore, Tfh cells proportion in untreated-RA and early-RA patients was markedly greater than HCs, when comparisons done without considering the definition markers, and also when Tfh cells were defined by the specified definition markers. While the proportion of Tfh cells by all definitions was higher in active-RA compared to HCs, analysis of two definitions, CD4(+)CXCR5(+) and CD4(+)CXCR5(+)ICOS(+), didn't show significant differences. Furthermore, higher proportion of Tfh cells defined by all definitions and a specified definition (CD4(+)CXCR5(+)PD-1(high)) was observed when S(+)RA compared to S(-)RA patients.Expert opinion:The results demonstrate that circulating Tfh are highly elevated in RA patients highlights its potential use as a biomarker and a target for RA therapy. | |
| 34648598 | Effects on health-related quality of life in the randomized, controlled crossover trial AD | 2021 | BACKGROUND: Patients with Rheumatoid Arthritis (RA) often report impaired health-related quality of life (HrQoL) such as difficulties in daily life, pain, fatigue and an affected social life. Even when lowering disease activity, pharmacological treatment does not always resolve these factors. OBJECTIVE: To investigate if a proposed anti-inflammatory diet improves HrQoL in patients with RA. DESIGN: In this controlled crossover trial, 50 patients were randomized to start with either an intervention diet (anti-inflammatory) or a control diet (usual Swedish intake) for ten weeks followed by a wash out period before switching to the other diet. Participants received food equivalent to ~1100 kcal/day, five days/week, and instructions to consume similarly for the remaining meals. HrQoL was evaluated using Health Assessment Questionnaire (HAQ), 36-item Short Form Survey (SF-36), Visual Analogue Scales (VAS) for pain, fatigue and morning stiffness, and a time scale for morning stiffness. RESULTS: Forty-seven participants completed ≥1 diet period and were included in the main analyses. No significant difference between intervention and control diet at end of diet periods was observed for any outcome. However, significant improvements were obtained for SF-36 Physical Functioning (mean:5.79, SE: 2.12, 95% CI: 1.58, 10.01) during the intervention diet period. When excluding participants with anti-rheumatic medication changes, the differences between diet periods increased for most outcomes, favoring the intervention diet period, and the difference for SF-36 Physical Functioning became significant (n = 25, mean:7.90, 95% CI:0.56, 15.24, p = 0.036). CONCLUSIONS: In main analyses, the proposed anti-inflammatory diet did not significantly improve HrQoL for patients with RA compared to control diet. In sub-analyses, significant improvements in physical functioning were detected. Larger studies with consistent medication use and in populations more affected by the disease may be needed to obtain conclusive evidence. | |
| 34504137 | Correlations between autoantibodies and the ATR-FTIR spectra of sera from rheumatoid arthr | 2021 Sep 9 | Rheumatoid arthritis (RA) is one of the most common autoimmune diseases worldwide. Due to high heterogeneity in disease manifestation, accurate and fast diagnosis of RA is difficult. This study analyzed the potential relationship between the infrared (IR) spectra obtained by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and the presence of autoantibodies and antibodies against urease in sera. Additionally, the wave number of the IR spectrum that enabled the best differentiation between patients and healthy blood donors was investigated. Using a mathematical model involving principal component analysis and discriminant analysis, it was shown that the presence of anti-citrullinated protein antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, and anti-nuclear antibodies correlated significantly with the wave numbers in the IR spectra of the tested sera. The most interesting findings derived from determination of the best predictors for distinguishing RA. Characteristic features included an increased reaction with urease mimicking peptides and a correspondence with particular nucleic acid bands. Taken together, the results demonstrated the potential application of ATR-FTIR in the study of RA and identified potential novel markers of the disease. |