Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 35440828 | Adaptation of Microarray Assay for Serum Amyloid a Analysis in Human Serum. | 2022 | Serum amyloid A is an inflammatory biomarker whose concentration changes during infectious and inflammatory diseases. SAA's tendency for aggregation and complex formation makes it difficult to determine its concentration in samples, especially when there is an increased level of it. Immunofluorescence SAA determination on a microarray was adapted for SAA quantification in human serum. Both the procedure and the diluent for the calibrator samples were chosen to obtain a dynamic range between 1 and 100 μg/mL. Mixtures of animal (rabbit, goat, mouse) sera with recombinant antigen diluted in certain concentrations were used for the calibrator samples. The method was tested using serum samples from 15 patients with rheumatoid arthritis or ankylosing spondylitis and 9 healthy donors. The results obtained on the microarray demonstrated a good correlation with the results determined by ELISA (Pearson's correlation coefficient is 0.93). The method developed could be a convenient tool for assessing SAA levels in a number of diseases, such as rheumatoid arthritis or infections of various etiologies, characterized by a significant increase in the level of this protein in the blood. The use of a microarray for the analysis allows the determination of the SAA concentration simultaneously with other inflammatory biomarkers. | |
| 35198780 | Effects of dexamethasone and acetylsalicylic acid on inflammation caused by Complete Freun | 2022 Feb | The naked mole rat (NMR) is a fossorial rodent that has been observed to have a unique nociceptive system in comparison to others. In this study, we explored on characterization of chronic inflammation in the NMR using Complete Freund's adjuvant (CFA) and investigated the effects of dexamethasone and acetylsalicylic acid on the resulting inflammation. The NMRs were injected with 0.1 ml of CFA subcutaneously in the right hind paw, and an equivalent volume of normal saline was injected to the control group. Swelling of the injected right hind limb was observed within 24 h of injection, which involved the tibiotarsal joint, palmar surface and the digits of the injected paw. Swelling persisted for 6 weeks of experimentation and peaked between day 14 and 21. The resulting inflammation affected the mobility, stance and joint rigidity of CFA treated NMRs in comparison to the control group. Treatment of the chronic phase of the inflammation from the 11(th) day with dexamethasone and acetylsalicylic acid showed no statistical significance in paw circumference compared to the control group, other than on a few, negligible occasions. The present data showed that CFA was able to induce chronic inflammation in the NMR, and the NMR could thus be established as a model for chronic inflammation. There is, however, need for more sensitive parameters to evaluate the effects of anti-inflammatory drugs. | |
| 35045550 | Comparison of 99mTc-methyl diphosphonate bone scintigraphy and 68Ga-DOTANOC PET/computed t | 2022 Apr 1 | OBJECTIVE: Tc-99m methyl diphosphonate (MDP) bone scintigraphy is used to assess disease activity in rheumatoid arthritis (RA). Somatostatin receptor (SSTR) expression in RA has been reported previously. SSTR-based PET/computed tomography (CT) may be superior to bone scintigraphy to know disease extent and in locating inflammatory joints that can be further targeted with peptide receptor radionuclide therapy thereby opening up new theranostic avenues. Based on these facts, the present study was designed to compare Tc-99m MDP bone scintigraphy and Ga-68 DOTANOC PET/CT in patients with RA. MATERIALS AND METHODS: Patients with a clinical diagnosis of RA were injected with 111-185 MBq of Ga-68 DOTANOC and 740 MBq of Tc-99m MDP intravenously. Images were acquired 30-45 min postinjection for Ga-68 DOTANOC on dedicated PET/CT scanners. Triple-phase bone scans were acquired on a dual-head gamma camera. PET/CT and MDP scan images were visually assessed by two experienced nuclear medicine physicians. RESULTS: Nineteen patients (16 women and 3 men) with a clinical diagnosis of RA were included in the study. Clinically, 196 joints in these 19 patients were diagnosed positive for RA. Of these 196 joints, Tc-99m MDP uptake was seen in 157 joints (80%). On Ga-68 DOTANOC scan, tracer uptake was seen in 151 of 196 joints (77%) with a lesion to background ratio of at least 2 in most of the joints. CONCLUSION: Ga-68 DOTANOC is equally good as an MDP scan for detection of RA with the added advantage of being used as a theranostic modality. However, further evaluation with a larger sample size and joint-to-joint comparison is warranted. | |
| 35467748 | A Case of Rheumatoid Arthritis With Bilateral Shoulder Bursitis Accompanied by Gas Image. | 2022 Apr 25 | We experienced a case of bilateral shoulder bursitis with gas images in a rheumatoid arthritis (RA) patient. A 60-year-old man with RA had been treated with weekly methotrexate (MTX) 10 mg and daily prednisolone (PSL) 10 mg for 7 months. Generalized pain, especially in the bilateral shoulder joints developed and exacerbated daily with increased CRP level. Despite the initiation of biweekly Sarilumab 200 mg, joint symptoms and CRP level continued to worsen. Computed tomography (CT) scan to determine the cause of severe shoulder inflammation revealed low absorption areas with contrast effects at the margins around the bilateral shoulder joints, accompanied by internal gas images. In addition, magnetic resonance imaging (MRI) demonstrated subacromial bursae and coracoid bursae, and bursitis leading to the suspicion of abscess formation depending on the presence of gas image. In spite of antimicrobial therapy, arthralgia did not improve and a CT-guided arthrocentesis of the left shoulder joint resulted in negative findings of infection in culture and pathological examinations. Switching treatment to intensive anti-inflammatory therapy with high-dose steroids and Etanercept finally improved symptom and CRP level associated with the reduction of low absorption areas and disappearance of gas images at bilateral shoulder joints. Our case indicated that bursitis with gas image in RA patients involves unusual pathophysiology and requires intensive anti-rheumatic treatment. | |
| 35023437 | Validation and characterization of venous thromboembolism diagnoses in the Swedish Nationa | 2022 Jan 13 | OBJECTIVE: To assess the validity of venous thromboembolism (VTE) diagnoses registered in the Swedish National Patient Register (NPR) in patients with rheumatoid arthritis (RA). METHOD: We performed a validation study using manual chart reviews to validate ICD-10 codes for VTE from the NPR. We took a random sample of 269 VTE events registered at hospitals in Region Stockholm from 2009 to 2018 in patients with RA. RESULTS: Medical records for all 269 VTE events were available for review. Overall, the positive predictive value (PPV) for a VTE diagnosis was 95%. For incident VTE events, the PPV was 87% and ranged from 80% to 98% across six more or less restricted alternative definitions of incident VTE event. Out of 235 confirmed incident VTE events, the vast majority were diagnosed independently of the RA disease (three cases occurred as a result of clinical work-up for a presumed RA-related sign or symptom, and in 17 cases did the work-up involve a rheumatologist). CONCLUSIONS: This study demonstrates high validity for VTE diagnoses recorded in the NPR for patients with RA, thus confirming that the NPR may be used to identify prevalent VTE as well as incident VTE events in patients with RA. Our results further demonstrate that in patients with RA, diagnoses of VTE are only marginally influenced by work-up related to the rheumatic disease, suggesting a modest impact of surveillance or diagnostic bias. | |
| 34929227 | Neuroinflammatory remodeling of the anterior cingulate cortex as a key driver of mood diso | 2022 Feb | Most gastrointestinal diseases and disorders (GIDD) are associated with depression, anxiety, and cognitive dysfunction. This suggests that shared features of GIDD, particularly chronic pain and inflammation, affect specific neural targets. The critical review of clinical and animal research presented here reveals that anterior cingulate cortex (ACC) is a primary target. It is particularly sensitive to neuroinflammation, and its function accounts for altered mental function emergent in GIDD. We propose that peripherally-triggered neuroinflammation normally signals injury/illness to ACC, which increases threat assessment and pain sensitivity to cope with increased vulnerability. Chronic peripheral inflammation over-drives this process, leading to long-term ACC structural remodeling, and excessive threat signaling. This evokes anxiodepressive phenotypes even without direct evidence of threats because ACC utilizes schemas to infer affective outcomes (e.g. pain) based on complex contextual information. This activates the autonomic nervous system, exacerbates immune dysfunction, and promotes further gut pathology. This theory provides a mechanistic account of bidirectional interactions among gastrointestinal, immunological, and neural systems in GIDD, and is likely applicable to other chronic inflammatory conditions. | |
| 35646960 | The Efficacy and Safety of Pirfenidone Combined With Immunosuppressant Therapy in Connecti | 2022 | OBJECTIVE: Interstitial lung disease (ILD) is a common manifestation of connective tissue disease (CTD) that manifests as several subtypes with significant differences in prognosis. It is necessary to evaluate the efficacy and safety of pirfenidone (PFD) combined with immunosuppressant (IS) in the treatment of CTD-ILD. METHODS: A total of 111 patients with CTD-ILD were enrolled, including those with systemic sclerosis (SSc), inflammatory myopathy (IIM), rheumatoid arthritis (RA), and other CTDs (such as systemic lupus erythematosus, primary Sjogren's syndrome, and undifferentiated CTD). After evaluation of the high-resolution computed tomography (HRCT), pulmonary function (PF), and basic disease activity, patients either were or were not prescribed PFD and were followed up regularly for 24 weeks. RESULTS: After 24 weeks of treatment, predicted forced vital capacity (FVC%) in the SSc-PFD group had improved by 6.60%, whereas this value was 0.55% in patients with SSc-no-PFD. The elevation in FVC% was also significant in IIM-PFD over the IIM-no-PFD controls (7.50 vs. 1.00%). The predicted diffusing capacity for carbon monoxide (DLCo%) of RA-PFD was enhanced by 7.40%, whereas that of RA-no-PFD decreased by 5.50%. When performing a subtype analysis of HRCT images, the change in FVC% among patients with SSc with a tendency toward usual interstitial pneumonia (UIP) was higher in those given PFD (SSc-PFD-UIP) than the no-PFD group (8.05 vs. -3.20%). However, in IIM patients with a non-UIP tendency, PFD displayed better therapeutic effects than the control (10.50 vs. 1.00%). DLCo% improved significantly in patients with the PFD-treated RA-non-UIP subtype compared with the patients with no-PFD (10.40 vs. -4.45%). Dichotomizing the patients around a baseline FVC% or DLCo% value of 70%, the PFD arm had a more improved FVC% than the no-PFD arm within the high-baseline-FVC% subgroups of patients with SSc and IIM (6.60 vs. 0.10%, 6.30 vs. 1.10%). In patients with RA-PFD, DLCo% showed a significant increase in the subgroup with low baseline DLCo% compared to that in patients with RA-no-PFD (7.40 vs. -6.60%). CONCLUSION: The response of PF to PFD varied between CTD-ILD subsets. Patients with SSc and IIM showed obvious improvements in FVC%, especially patients with SSc-UIP and IIM-non-UIP. In RA, the subsets of patients with non-UIP and a lower baseline DLCo% most benefited from PFD. | |
| 35606567 | From risk to chronicity: evolution of autoreactive B cell and antibody responses in rheuma | 2022 May 23 | The presence of disease-specific autoantibody responses and the efficacy of B cell-targeting therapies in rheumatoid arthritis (RA) indicate a pivotal role for B cells in disease pathogenesis. Important advances have shaped our understanding of the involvement of autoantibodies and autoreactive B cells in the disease process. In RA, autoantibodies target antigens with a variety of post-translational modifications such as carbamylation, acetylation and citrullination. B cell responses against citrullinated antigens generate anti-citrullinated protein antibodies (ACPAs), which are themselves modified in the variable domains by abundant N-linked glycans. Insights into the induction of autoreactive B cells against antigens with post-translational modifications and the development of autoantibody features such as isotype usage, epitope recognition, avidity and glycosylation reveal their relationship to particular RA risk factors and clinical phenotypes. Glycosylation of the ACPA variable domain, for example, seems to predict RA onset in ACPA(+) healthy individuals, possibly because it affects B cell receptor signalling. Moreover, ACPA-expressing B cells show dynamic phenotypic changes and develop a continuously proliferative and activated phenotype that can persist in patients who are in drug-induced clinical remission. Together, these findings can be integrated into a conceptual framework of immunological autoreactivity in RA, delineating how it develops and persists and why disease activity recurs when therapy is tapered or stopped. | |
| 35258557 | A systematic review of live vaccine outcomes in infants exposed to biologic disease modify | 2022 Mar 8 | OBJECTIVES: Transplacental passage of certain biologic- and targeted synthetic DMARDs leads to detectable levels in the neonate, which may impact on the safety of live vaccines. Guidelines advise delaying live vaccine administration in biologic exposed infants until they are 7 months old. METHODS: A systematic review of Embase, Medline and Cochrane identified live vaccine outcomes in infants exposed to biologic or targeted synthetic DMARDs in-utero. RESULTS: Studies included 276 in-utero exposures to adalimumab, certolizumab, etanercept, infliximab, golimumab, tocilizumab and ustekinumab. Live vaccine exposures <12 months of age included BCG (n = 215), rotavirus (n = 46) and MMR (n = 12). We identified no reactions following MMR, 7 mild reactions to rotavirus vaccination, and 8 reactions to BCG including one death. All infants with an adverse reaction to BCG had been exposed to infliximab in-utero, and 6 had received BCG in the first month of life. A freedom of information request to the Medicines and Healthcare products Regulatory Agency revealed 4 fatal disseminated BCG infections in infants exposed to TNF inhibitors in-utero, including infliximab, adalimumab and one unspecified TNF inhibitor. CONCLUSION: Most evidence for clinically harmful effect was for early administration of the BCG vaccine to infants exposed in-utero to TNF inhibitors with high transplacental transfer rates. | |
| 34998430 | Research progress of the application of mesenchymal stem cells in chronic inflammatory sys | 2022 Jan 8 | Chronic inflammatory systemic diseases are the result of the body's immune imbalance, with a long course and recurring episodes. Immunosuppressants are the main treatment, but not all patients respond well to it. Being capable of both self-renewal and differentiation into multiple tissue cells and low immunogenicity, mesenchymal stem cell is a promising treatment for chronic inflammatory systemic diseases. In this article, we describe the research progress and clinical application of mesenchymal stem cells in chronic inflammatory systemic diseases and look for influencing factors and biomarkers that can predict the outcome of patient with mesenchymal stem cell transplantation. | |
| 33866600 | A review of signaling and transcriptional control in T follicular helper cell differentiat | 2022 Jan | T follicular helper (Tfh) cells are a critical component of adaptive immunity and assist in optimal Ab-mediated defense. Multiple effector functions of Tfh support germinal center B cell survival, Ab class switching, and plasma cell maturation. In the past 2 decades, the phenotype and functional characteristics of GC Tfh have been clarified allowing for robust studies of the Th subset including activation signals and environmental cues controlling Tfh differentiation and migration during an immune response. A unique, 2-step differentiation process of Tfh has been proposed but the mechanisms underlying transition between unstable Tfh precursors and functional mature Tfh remain elusive. Likewise, newly identified transcriptional regulators of Tfh development have not yet been incorporated into our understanding of how these cells might function in disease. Here, we review the signals and downstream transcription factors that shape Tfh differentiation including what is known about the epigenetic processes that maintain Tfh identity. It is proposed that further evaluation of the stepwise differentiation pattern of Tfh will yield greater insights into how these cells become dysregulated in autoimmunity. | |
| 35340672 | Sinobronchial Syndrome Patients with Suspected Non-Tuberculous Mycobacterium Infection Exa | 2022 | BACKGROUND: Exophiala dermatitidis is an environmental black fungus that rarely causes respiratory infections, yet its pathophysiological features and treatment regimens have not been established. CASE SERIES: Two cases of exacerbations of chronic bronchitis and sinusitis due to E. dermatitidis infection in Japan are presented. Both patients were women, and non-tuberculous Mycobacterium (NTM) infection was suspected based on chest radiological findings, but E. dermatitidis was detected from bronchial lavage fluid and nasal mucus, respectively. Both cases were successfully treated by antifungal agents such as liposomal amphotericin B, voriconazole, and itraconazole, but clarithromycin, rifampicin, ethambutol, and sitafloxacin for NTM were not effective. CONCLUSION: E. dermatitidis can become a respiratory pathogen, especially in patients with chronic sinobronchial syndrome. | |
| 35486218 | Cannabis for Rheumatic Disease Pain: a Review of Current Literature. | 2022 May | PURPOSE OF REVIEW: Changing attitudes about marijuana have led to an increase in use of medicinal marijuana, especially for painful chronic conditions. Patients ask rheumatologists for guidance on this topic. This review provides up-to-date information on the safety and efficacy of medicinal cannabis for rheumatic disease pain. RECENT FINDINGS: The number of publications related to rheumatic disease and cannabis has increased, but recent literature skews heavily toward reviews vs primary research. Data supporting a role for cannabinoids in rheumatic disease continue to grow. Observational and survey studies show increased use of medicinal cannabis, both by people with rheumatic disease and the general population, and suggest that patients find these treatments beneficial. Prospective studies, however, including randomized controlled clinical trials, are rare and sorely needed. As medicinal cannabis use for rheumatic diseases rises, despite lack of evidence, we review the sparse data available and provide tips for conversations about medicinal cannabis for rheumatologists. | |
| 35256384 | Persistently normal blood tests in patients taking methotrexate for RA or azathioprine for | 2022 Jan 24 | BACKGROUND: Disease-modifying anti-rheumatic drugs (DMARDs), including methotrexate and azathioprine, are commonly used to treat rheumatoid arthritis (RA) and inflammatory bowel disease (IBD). Blood-test safety monitoring is mainly undertaken in primary care. Normal blood results are common. AIM: To determine the frequency and associations of persistently normal blood tests in patients with RA prescribed methotrexate, and patients with IBD prescribed azathioprine. DESIGN AND SETTING: Two-year retrospective study of a cohort taken from an electronic pseudonymised primary care/laboratory database covering >1.4 million patients across Hampshire, UK. METHOD: Patients with RA and IBD, and associated methotrexate and azathioprine prescriptions, respectively, were identified. Tests and test thresholds recommended by the National Institute for Health and Care Excellence were applied. Persistent normality was defined as no abnormalities of any tests nor alanine aminotransferase (ALT), white blood count (WBC), neutrophils, and estimated glomerular filtration rate (eGFR) individually. Logistic regression was used to identify associations with test normality. RESULTS: Of 702 265 adults, 7102 had RA and 8597 had IBD. In total, 3001 (42.3%) patients with RA were prescribed methotrexate and 1162 (13.5%) patients with IBD were prescribed azathioprine; persistently normal tests occurred in 1585 (52.8%) and 657 (56.5%) of the populations, respectively. In patients with RA on methotrexate, 585 (19.5%) had eGFR, 219 (7.3%) ALT, 217 (7.2%) WBC, and 202 (6.7%) neutrophil abnormalities. In patients with IBD on azathioprine, 138 (11.9%) had WBC, 88 (7.6%) eGFR, 72 (6.2%) ALT, and 65 (5.6%) neutrophil abnormalities. Those least likely to have persistent test normality were older and/or had comorbidities. CONCLUSION: Persistent test normality is common when monitoring these DMARDs, with few hepatic or haematological abnormalities. More stratified monitoring approaches should be explored. | |
| 35434040 | Trends and frontiers of research on pharmacoeconomics from 2012-2021: a scientometric anal | 2022 Mar | BACKGROUND: Research on pharmacoeconomics (PE) promotes the rational allocation of medical resources, which has received attention in the last decade. We conducted a scientometric analysis of PE to determine the current status and frontiers, and promote cooperation and development. METHODS: The Web of Science Core Collection-Science Citation Index Expanded was adopted to retrieve publications associated with PE from 2012-2021. After screening publications, CiteSpace 3.8.R3 was used to conduct a scientometric analysis. We analyzed terms, including publications and citations, countries/regions, institutions, journals, authors, keywords, and references. RESULTS: In total, 4,715 documents published from 2012-2021 were included in this study, of which 3,829 were articles and 886 were reviews. The documents were cited 54,596 times, at an average of 11.58 times per document. 121 countries/regions and 410Â institutions were involved. The top 3 countries/regions by the number of publications were the United States of America (n=1,790), England (n=601), and China (n=403), while the institution with the most publications was Pfizer. Pharmacoeconomics was the main journal of PE, with 310 publications in all, and the top 3 cited journals were New England Journal of Medicine (citation times =1,620), Value in Health (citation times =1,306), and Lancet (citation times =1,255). Bin Wu was the most productive author (n=16), while World Health Organization was the most influential author (citation times =387). 524 keywords altogether were found, and the top 3 keywords by frequency were therapy (frequency =318), impact (frequency =305), and cost-effectiveness (frequency =296). The keyword "modifying antirheumatic drug" associated with rheumatoid arthritis (RA) has continued bursting from 2016-2021. Guide to the methods of technology appraisal 2013 by the National Institute for Health and Care Excellence, was the most frequently cited publication on PE (citation times =65). Cluster 0 labeled as "cost-effectiveness analysis" (CEA) was the largest and latest cluster, and its citing articles focused on the CEA of first-line treatment for non-small cell lung cancer (NSCLC). CONCLUSIONS: The economic analysis of disease-modifying antirheumatic drugs related to RA was a popular topic in the last 6 years, and CEA of NSCLC first-line treatment was at the frontier of PE. | |
| 34983770 | Association between hormone replacement therapy and carpal tunnel syndrome: a nationwide p | 2022 Jan 4 | OBJECTIVE: Carpal tunnel syndrome (CTS) is the most common compressive focal mononeuropathy, and the increased incidence in postmenopausal and pregnant women suggests its association with oestrogen. The objective of this study is to evaluate the relationship between hormone replacement therapy (HRT) and the occurrence of CTS. DESIGN: Population-based case-control study. SETTING: Nationwide health insurance programme operated by the government with a near 100% coverage rate. PARTICIPANTS: We identified women ≥45 years old in the Health Insurance Research Database of Taiwan, which contains data on a representative sample of one million enrollees. After exclusion of those who were diagnosed with CTS before the prescription of HRT, a total of 118 309 participants were included and followed up for 15 years starting from 1 January 1996. Both HRT and occurrence of CTS were identified using the insurance claims. MAIN OUTCOME MEASURES: We identified incident patients of CTS and evaluated the association between HRT and CTS by calculating the OR. RESULTS: Of the 4535 participants who developed CTS during the study period, 2334 (51.5%) were HRT recipients. In participants without CTS, the proportion of HRT recipients was 28.1%, yielding an OR of 2.72 with a 95% CI of 2.56 to 2.88. After adjustment for age, diabetes, rheumatoid arthritis, hypothyroidism, gout and obesity, the OR of CTS associated with HRT was 2.04 (95% CI 1.91 to 2.17). While HRT, diabetes, rheumatoid arthritis and gout had similar effects on CTS across all age groups, hypothyroidism and obesity had different effects on different groups. CONCLUSION: This study observed a positive association between HRT and CTS, independent of age, diabetes, rheumatoid arthritis, hypothyroidism, gout and obesity. While the ORs of CTS associated with HRT were similar across age groups, those associated with hypothyroidism and obesity were not, indicating effect modifications by age. | |
| 35023445 | Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogen | 2022 Jan 13 | OBJECTIVE: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA. METHOD: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor. RESULTS: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1β and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05). CONCLUSIONS: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA. | |
| 35143117 | Obesity and Response to Advanced Therapies in Rheumatoid Arthritis. | 2022 Feb 10 | PURPOSE: We performed a study of Tumor-Necrosis Factor inhibitors (TNFi) compared to non-TNFi biologic therapies in rheumatoid arthritis and tested whether body mass index (BMI) modified the effect of each therapy. METHODS: We utilized data from CorEvitas. We studied three clinical outcomes based on the Clinical Disease Activity Index (CDAI) at 6 months from therapy initiation: 1) achievement of low disease activity (LDA), 2) a change as large as the minimal clinically important difference (MCID), and 3) the absolute change. We categorized BMI and utilized restricted cubic splines to consider non-linear associations. We used linear and logistic regression to evaluate associations with response, adjusting for confounders. To determine if comparative effectiveness of therapy varied by BMI, we tested for interactions between BMI and class of therapy. RESULTS: The sample included 2891 TNFi and 3010 non-TNFi initiators. Among all initiators, those with severe obesity experienced lower odds of achieving LDA or MCID and less improvement in CDAI, although associations were attenuated with adjustment. Low BMI was associated with reduced response rates in adjusted models including lower odds of LDA [OR (95% CI): 0.32 (0.15,0.71) p=0.005]. Analyses stratified by TNFi and non-TNFi therapies demonstrated no differences in clinical response rates for TNFi v. non-TNFi across BMI categories (all p for interaction >0.05). Estimates for non-TNFi biologics fit within the 95% CI for TNFi. CONCLUSIONS: This study observed lower response rates among obese and underweight patients and no evidence of a superior effect of non-TNFi therapy over TNFi therapy in particular BMI categories. | |
| 35407368 | Controversial Aspects of Diagnostics and Therapy of Arthritis of the Temporomandibular Joi | 2022 Mar 22 | INTRODUCTION: Due to potentially severe sequelae (impaired growth, condylar resorption, and ankylosis) early diagnosis of chronic rheumatic arthritis of the temporomandibular joint (TMJ) and timely onset of therapy are essential. AIM: Owing to very limited evidence the aim of the study was to identify and discuss controversial topics in the guideline development to promote further focused research. METHODS: Through a systematic literature search, 394 out of 3771 publications were included in a German interdisciplinary guideline draft. Two workgroups (1: oral and maxillofacial surgery, 2: interdisciplinary) voted on 77 recommendations/statements, in 2 independent anonymized and blinded consensus phases (Delphi process). RESULTS: The voting results were relatively homogenous, except for a greater proportion of abstentions amongst the interdisciplinary group (p < 0.001). Eighty-four percent of recommendations/statements were approved in the first round, 89% with strong consensus. Fourteen recommendations/statements (18.2%) required a prolonged consensus phase and further discussion. DISCUSSION: Contrast-enhanced MRI was confirmed as the method of choice for the diagnosis of TMJ arthritis. Intraarticular corticosteroid injection is to be limited to therapy-refractory cases and single injection only. In adults, alloplastic joint replacement is preferable to autologous replacement. In children/adolescents, autologous reconstruction may be performed lacking viable alternatives. Alloplastic options are currently still considered experimental. | |
| 35459695 | Isolation of HLA-DR-naturally presented peptides identifies T-cell epitopes for rheumatoid | 2022 Apr 22 | OBJECTIVE: Rheumatoid arthritis (RA) immunopathogenesis revolves around the presentation of poorly characterised self-peptides by human leucocyte antigen (HLA)-class II molecules on the surface of antigen-presenting cells to autoreactive CD4 +T cells. Here, we analysed the HLA-DR-associated peptidome of synovial tissue (ST) and of dendritic cells (DCs) pulsed with synovial fluid (SF) or ST, to identify potential T-cell epitopes for RA. METHODS: HLA-DR/peptide complexes were isolated from RA ST samples (n=3) and monocyte-derived DCs, generated from healthy donors carrying RA-associated shared epitope positive HLA-DR molecules and pulsed with RA SF (n=7) or ST (n=2). Peptide sequencing was performed by high-resolution mass spectrometry. The immunostimulatory capacity of selected peptides was evaluated on peripheral blood mononuclear cells from patients with RA (n=29) and healthy subjects (n=12) by flow cytometry. RESULTS: We identified between 103 and 888 HLA-DR-naturally presented peptides per sample. We selected 37 native and six citrullinated (cit)-peptides for stimulation assays. Six of these peptides increased the expression of CD40L on CD4 +T cells patients with RA, and specifically triggered IFN-γ expression on RA CD4 +T cells compared with healthy subjects. Finally, the frequency of IFN-γ-producing CD4 +T cells specific for a myeloperoxidase-derived peptide showed a positive correlation with disease activity. CONCLUSIONS: We significantly expanded the peptide repertoire presented by HLA-DR molecules in a physiologically relevant context, identifying six new epitopes recognised by CD4 +T cells from patients with RA. This information is important for a better understanding of the disease immunopathology, as well as for designing tolerising antigen-specific immunotherapies. |