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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| 35160112 | Subclinical Atherosclerosis Measure by Carotid Ultrasound and Inflammatory Activity in Pat | 2022 Jan 27 | OBJECTIVE: To compare the effect of inflammation on subclinical atherosclerosis using carotid ultrasound in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Cross-sectional study including 347 participants (148 RA, 159 SpA, and 40 controls). We measured the carotid intima media thickness (cIMT) and detection of atheromatous plaques using carotid ultrasound. We recorded disease activity (DAS28-CRP/ASDAS-CRP) and traditional cardiovascular risk factors. We performed descriptive, bivariate, and linear multivariate analyses (dependent variable: cIMT) to evaluate the influence of diagnosis on cIMT in all patients. Two additional multivariate analyses were performed by stratifying patients according to their inflammatory activity. RESULTS: cIMT correlated with the mean CRP during the previous 5 years in RA, but not with CRP at the cut-off date. We did not find such differences in patients with SpA. The first multivariate model revealed that increased cIMT was more common in patients with RA than in those with SpA (β coefficient, 0.045; 95% confidence interval (95% CI), 0.0002-0.09; p = 0.048) after adjusting for age, sex, disease course, and differential cardiovascular risk factors (arterial hypertension, smoking, statins, and corticosteroids). The second model revealed no differences in cIMT between the 2 groups of patients classified as remission-low activity (β coefficient, 0.020; 95% CI, -0.03 to 0.080; p = 0.500). However, when only patients with moderate-high disease activity were analysed, the cIMT was 0.112 mm greater in those with RA (95% CI, 0.013-0.212; p = 0.026) than in those with SpA after adjusting for the same variables. CONCLUSIONS: Subclinical atherosclerosis measured by carotid ultrasound in patients with RA and SpA is comparable when the disease is well controlled. However, when patients have moderate-high disease activity, cIMT is greater in patients with RA than in those with SpA after adjusting for age, sex, disease course, and cardiovascular risk factors. Our results point to greater involvement of disease activity in subclinical atherosclerosis in patients with RA than in those with SpA. | |
| 35016780 | Type I Interferons in Autoimmunity. | 2022 Mar | Dysregulated IFN-1 responses play crucial roles in the development of multiple forms of autoimmunity. Many patients with lupus, systemic sclerosis, Sjogren's syndrome, and dermatomyositis demonstrate enhanced IFN-1 signaling. IFN-1 excess is associated with disease severity and autoantibodies and could potentially predict response to newer therapies targeting IFN-1 pathways. In this review, we provide an overview of the signaling pathway and immune functions of IFN-1s in health and disease. We also review the systemic autoimmune diseases classically associated with IFN-1 upregulation and current therapeutic strategies targeting the IFN-1 system. | |
| 33597197 | Tear secretion from the lacrimal gland: variations in normal versus dry eyes. | 2022 Jun | PURPOSE: To investigate the secretory status of the main lacrimal gland in healthy and dry eye disease (DED) via fluorescein-assisted direct assessment of tear secretion from the palpebral lobes. METHODS: Included were 25 healthy subjects (50 lobes) and 75 subjects with DED (cicatrising conjunctivitis (CC, n=27), evaporative dry eyes (EDE, n=25) and Sjogren's syndrome (SS, n=23)). Analysed parameters included number and location of ductular openings, tear flow rate per gland and per ductule, and the time lag for the initiation of secretion. RESULTS: Ductular openings could be observed in all patients with EDE and healthy subjects whereas only 33% (18/54) glands of CC patients and 67% glands (31/46) patients with SS revealed ductules. The median number of ductules per lobe was 4 in normal (range 3-5), 3 in EDE (3-6), 1 in SS (0-3) and 0 in CC group (0-3) (p<0.000001). The median tear flow rate per lobe in CC (0.00 [Formula: see text]) and SS (0.21 [Formula: see text]) was significantly lesser than normal lobes (1.05 [Formula: see text], and EDE (0.99 [Formula: see text] eyes. The tear flow rate differed significantly between SS and CC group (p<0.0001). The maximum time lag occurred in the CC group (median, 20 s), followed by the SS group (median, 1.5 s) whereas the EDE group had similar time lag (<1 s) as of normal glands (p<0.0001). CONCLUSION: Direct assessment of tear secretion from the palpebral lobe demonstrates significant differences between EDE, aqueous deficient dry eye and dry eye in CC. | |
| 35329893 | Herb-Drug Interaction in Inflammatory Diseases: Review of Phytomedicine and Herbal Supplem | 2022 Mar 12 | Many people worldwide use plant preparations for medicinal purposes. Even in industrialized regions, such as Europe, where conventional therapies are accessible for the majority of patients, there is a growing interest in and usage of phytomedicine. Plant preparations are not only used as alternative treatment, but also combined with conventional drugs. These combinations deserve careful contemplation, as the complex mixtures of bioactive substances in plants show a potential for interactions. Induction of CYP enzymes and pGP by St John's wort may be the most famous example, but there is much more to consider. In this review, we shed light on what is known about the interactions between botanicals and drugs, in order to make practitioners aware of potential drug-related problems. The main focus of the article is the treatment of inflammatory diseases, accompanied by plant preparations used in Europe. Several of the drugs we discuss here, as basal medication in chronic inflammatory diseases (e.g., methotrexate, janus kinase inhibitors), are also used as oral tumor therapeutics. | |
| 35566422 | The Importance of Foot Function Assessment Using the Foot Function Index-Revised Short For | 2022 Apr 20 | BACKGROUND: Foot problems may have a substantial negative impact on rheumatoid arthritis (RA) patients' mobility. They affect walking and the functional capacity to perform daily tasks. METHODS: This study included 61 patients with RA and foot pain or swelling. The study group comprised 37 patients (aged 54.3 ± 9.5 years) with foot lesions, as demonstrated in an ultrasound, and the control group comprised 24 patients (aged 57.3 ± 11.5 years) without foot lesions. The patients' health statuses were evaluated with the Foot Function Index-Revised Short Form (FFI-RS), the Polish version of the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Disease Activity Score 28 (DAS 28). RESULTS: The FFI-RS showed significant differences between the study and control groups in total results, as well as in the pain and stiffness subscales. Subsequent analyses showed numerous significant correlations. The FFI-RS total results correlated with the HAQ's standing up, walking, and total results. The FFI-RS pain results correlated with the social issues and HAQ's total results. The FFI-RS difficulty results correlated with the disease's duration. In the study group, there were significant correlations of the FFI-RS stiffness, difficulty, and social issues results with the HAQ's standing up, walking, and total results, and also of the FFI-RS activity limitation results with the HAQ's standing up results. In the control group, there were correlations of the FFI-RS stiffness, difficulty, and activity limitation results with the HAQ's walking and total results. Finally, in the study group, we also found correlations of the FFI-RS total, pain, stiffness, difficulty, and social issues results with the Visual Analog Scale (VAS) results, as well as of the FFI-RS total results with the DAS 28 results. CONCLUSIONS: The FFI-RS is an effective tool for assessing RA patients' functional status and can be used to evaluate treatment effects. The FFI-RS detected RA-related changes in the foot joint function in patients without foot lesions, as assessed by ultrasound. | |
| 35294030 | Non-Drug and Surgical Treatment Algorithm and Recommendations for the 2020 Update of the J | 2022 Mar 16 | OBJECTIVES: The aim of this study was to update the Japan College of Rheumatology (JCR) clinical practice guidelines (CPGs) for the management of rheumatoid arthritis (RA) and prepare an algorithm for non-drug and surgical treatments. This article is a digest version of the guidelines. METHODS: The Japanese Ministry of Health, Labour and Welfare's research group, in collaboration with the JCR, used the Grading of Recommendations, Assessment, Development, and Evaluation method to update the 2014 JCR CPG for RA. The consensus was formed by CPG panel members. RESULTS: We raised 19 clinical questions regarding non-drug and surgical treatments for RA and developed recommendations. The treatments included exercise therapy; occupational therapy; joint injection of corticosteroids; and orthopedic surgeries including cervical spine surgery, wrist and foot arthroplasty, ankle arthrodesis, and replacement arthroplasty of the shoulder, elbow, finger, hip, knee, and ankle. Recommendations regarding the risks of surgery and perioperative discontinuation of medications have also been developed. Based on these recommendations, we created an original algorithm for the non-drug and surgical treatment of RA. CONCLUSIONS: These recommendations are expected to serve rheumatologists, health care professionals, and patients with RA as tools for shared decision-making to treat residual limb joint symptoms and functional impairment. | |
| 35083506 | Optical imaging compared to clinical examination in 484 rheumatoid arthritis patients: the | 2022 Jan 27 | The Handscan is a novel objective optical imaging device for disease follow-up and management in rheumatoid arthritis patients. We aim to examine the association between the baseline outcomes of the Handscan, disease activity levels and joint swelling. The Handscan measures differences in laser light absorption between joints of fingers and wrists and adjacent reference tissue, indicating the presence or absence of inflammation. The device gives an optical spectral transmission (OST) index per joint. The average of these indices is represented in the total optical score (TOS). Associations between TOS and DAS28 at subject level and OST and swelling at joint level were examined. 484 RA patients were included. Compared to patients with high disease activity (defined by DAS28), TOS was significantly lower in patients with moderate (estimated coefficient B: - 7.09, P < 0.001), low disease activity (B: - 6.99, P < 0.001) and patients in remission (B: - 7.72, P < 0.001) but could not distinguish between the latter three disease states. TOS was significantly lower in females (B: - 3.2, P < 0.001). OST was significantly higher in swollen than non-swollen joints (B: 0.28, P < 0.001). TOS was significantly higher in patients with high disease activity than in those in remission or with low and moderate disease activity. The difference in TOS between males and females should be accounted for in the interpretation of this outcome. The OST at joint level discriminates swollen from non-swollen joints and could be a more promising tool than the overall optical activity reflected in TOS. | |
| 34346525 | Differential expression and regulation of MS4A family members in myeloid cells in physiolo | 2022 Apr | The MS4A gene family encodes 18 tetraspanin-like proteins, most of which with unknown function. MS4A1 (CD20), MS4A2 (FcεRIβ), MS4A3 (HTm4), and MS4A4A play important roles in immunity, whereas expression and function of other members of the family are unknown. The present investigation was designed to obtain an expression fingerprint of MS4A family members, using bioinformatics analysis of public databases, RT-PCR, and protein analysis when possible. MS4A3, MS4A4A, MS4A4E, MS4A6A, MS4A7, and MS4A14 were expressed by myeloid cells. MS4A6A and MS4A14 were expressed in circulating monocytes and decreased during monocyte-to-Mϕ differentiation in parallel with an increase in MS4A4A expression. Analysis of gene expression regulation revealed a strong induction of MS4A4A, MS4A6A, MS4A7, and MS4A4E by glucocorticoid hormones. Consistently with in vitro findings, MS4A4A and MS4A7 were expressed in tissue Mϕs from COVID-19 and rheumatoid arthritis patients. Interestingly, MS4A3, selectively expressed in myeloid precursors, was found to be a marker of immature circulating neutrophils, a cellular population associated to COVID-19 severe disease. The results reported here show that members of the MS4A family are differentially expressed and regulated during myelomonocytic differentiation, and call for assessment of their functional role and value as therapeutic targets. | |
| 34752968 | 7-Hydroxycoumarin mitigates the severity of collagen-induced arthritis in rats by inhibiti | 2022 Jan | BACKGROUND: 7-Hydroxycoumarin (7-HC) as a coumarin compound is widely found in Chinese herbs and exhibits diverse biological activities. Promoting cell apoptosis of fibroblast-like synoviocytes (FLS) is a meaningful strategy for rheumatoid arthritis (RA). Though the protective effect of 7-HC on RA experimental models has been reported, the specific mechanisms, especially the possible relationships of this effect to regulating FLS proliferation and apoptosis, still need clarification. PURPOSE: This study clarified the therapeutic effects of 7-HC on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. METHODS: In vivo, 7-HC (15, 30 or 60 mg/kg) was intraperitoneally given to CIA rats, and its therapeutic effect and anti-inflammatory activity were evaluated. Ki67 immunohistochemistry, TUNEL assay and synovial proteins detection were conducted. In vitro, after treating with 7-HC (20, 40 or 80 μM) in TNF-α-stimulated RA FLS (MH7A cell line), cell proliferation and apoptosis were examined. The involvement of Wnt/β-catenin pathway was checked in vivo and in vitro. RESULTS: 7-HC attenuated the severity of rat CIA, evidenced by the reduction of paw swelling, arthritis index, joint damage, collagen type II antibody serum level, and IL-1β, IL-6, TNF-α production in serum and synovium. Particularly, 7-HC in vivo had anti-proliferative and pro-apoptotic effects on CIA rat synovial cells, indicated by reduced synovial Ki67 expression, raised synovial apoptosis index, decreased Bcl-2 protein level and increased level of Bax and cleaved caspase 3 protein. Further, 7-HC in vitro suppressed proliferation and promoted apoptosis of TNF-α-stimulated MH7A cells by regulating the mitochondrial pathway. Mechanistically, 7-HC treatment inhibited Wnt/β-catenin pathway, suggested by the reduction of pathway-related proteins (e.g. Wnt1, LRP6, p-GSK-3β (Ser9), β-catenin, cyclin D1 and c-Myc), the recovery of GSK-3β activity and the inhibition of β-catenin nuclear translocation. As expected, combined use of lithium chloride, an activator of Wnt/β-catenin signaling, reversed the anti-proliferative and pro-apoptotic effects of 7-HC in vitro. CONCLUSION: 7-HC relieved the severity of rat CIA by inhibiting cell proliferation and inducing apoptosis of rheumatoid FLS via inhibition of Wnt/β-catenin pathway. | |
| 35079379 | TGF-β-activated kinase-1 inhibitor LL-Z1640-2 reduces joint inflammation and bone destruc | 2022 | OBJECTIVES: Aberrant NLRP3 inflammasome activation has been demonstrated in rheumatoid arthritis (RA), which may contribute to debilitating inflammation and bone destruction. Here, we explored the efficacy of the potent TGF-β-activated kinase-1 (TAK1) inhibitor LL-Z1640-2 (LLZ) on joint inflammation and bone destruction in collagen-induced arthritis (CIA). METHODS: LL-Z1640-2 was administered every other day in CIA mice. Clinical and histological evaluation was performed. Priming and activation of NLRP3 inflammasome and osteoclastogenic activity were assessed. RESULTS: NLRP3 inflammasome formation was observed in synovial macrophages and osteoclasts (OCs) in CIA mice. TACE and RANKL were also overexpressed in synovial macrophages and fibroblasts, respectively, in the CIA joints. Treatment with LLZ mitigated all the above changes. As a result, LLZ markedly suppressed synovial hypertrophy and pannus formation to alleviate pain and inflammation in CIA mice. LLZ could block the priming and activation of NLRP3 inflammasome in RAW264.7 macrophage cell line, primary bone marrow macrophages and OCs upon treatment with LPS followed by ATP, thereby suppressing their IL-1β production. LLZ also suppressed LPS-induced production of TACE and TNF-α in bone marrow macrophages and abolished IL-1β-induced production of MMP-3, IL-6 and RANKL in synovial fibroblasts. In addition, LLZ directly inhibits RANKL-mediated OC formation and activation. CONCLUSION: TAK1 inhibition with LLZ may become a novel treatment strategy to effectively alleviate inflammasome-mediated inflammation and RANKL-induced osteoclastic bone destruction in joints alongside its potent suppression of TNF-α and IL-6 production and proteinase-mediated pathological processes in RA. | |
| 34843735 | Blocking IAg(7) class II major histocompatibility complex by drug-like small molecules all | 2022 Jan 1 | BACKGROUND: Sjögren's syndrome (SjS) is an autoimmune disease with a strong genetic association. To date, no vaccine or therapeutic agent exists to cure SjS, and patients must rely on lifelong therapies to treat symptoms. Human leukocyte antigens (HLA) are primary susceptibility loci that form the genetic basis for many autoimmune diseases, including SjS. In this study, we sought to determine whether blocking MHC class II IAg(7) antigen presentation in the NOD mouse would alleviate SjS by preventing the recognition of autoantigens by pathogenic T cells. METHODS: Mapping of the antigenic epitopes of Ro60 autoantigen to IAg(7) of the NOD mice was performed using structural modeling and in-vitro stimulation. Tetraazatricyclo-dodecane (TATD) and 8-Azaguanine (8-Aza) were previously identified as potential binders to IA(g7) of the NOD mice using in silico drug screening. Mice were treated with 20mgs/kg via IP every day five days/week for 23 weeks. Disease profiling was conducted. FINDINGS: Specific peptides of Ro60 autoantigen were identified to bind to IAg(7) and stimulated splenocytes of the NOD mice. Treating NOD mice with TATD or 8-Azaguanine alleviated SjS symptoms by improving salivary and lacrimal gland secretory function, decreasing the levels of autoantibodies, and reducing the severity of lymphocytic infiltration in the salivary and lacrimal glands. INTERPRETATION: This study presents a novel therapeutic approach for SjS by identifying small molecules capable of inhibiting T cell response via antigen-specific presentation. FUNDING: CQN is supported financially in part by PHS grants AI130561, DE026450, and DE028544 from the National Institutes of Health. | |
| 35602512 | RNA-seq and Network Analysis Reveal Unique Chemokine Activity Signatures in the Synovial T | 2022 | PURPOSE: This study aimed to provide a comprehensive understanding of the genome-wide expression patterns in the synovial tissue samples of patients with rheumatoid arthritis (RA) to investigate the potential mechanisms regulating RA occurrence and development. METHODS: Transcription profiles of the synovial tissue samples from nine patients with RA and 15 patients with osteoarthritis (OA) (control) from the East Asian population were generated using RNA sequencing (RNA-seq). Gene set enrichment analysis (GSEA) was used to analyze all the detected genes and the differentially expressed genes (DEGs) were identified using DESeq. To further analyze the DEGs, the Gene Ontology (GO) functional enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. The protein-protein interaction (PPI) network of the DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) and the hub genes were identified by topology clustering with the Molecular Complex Detection (MCODE)-Cytoscape. The most important hub genes were validated using quantitative real-time PCR (qRT-PCR). RESULTS: Of the 17,736 genes detected, 851 genes were identified as the DEGs (474 upregulated and 377 downregulated genes) using the false discovery rate (FDR) approach. GSEA revealed that the significantly enriched gene sets that positively correlated with RA were CD40 signaling overactivation, Th1 cytotoxic module, overactivation of the immune response, adaptive immune response, effective vs. memory CD8+ T cells (upregulated), and naïve vs. effective CD8+ T cells (downregulated). Biological process enrichment analysis showed that the DEGs were significantly enriched for signal transduction (P = 3.01 × 10(-6)), immune response (P = 1.65 × 10(-24)), and inflammatory response (P = 5.76 × 10(-10)). Molecule function enrichment analysis revealed that the DEGs were enriched in calcium ion binding (P = 1.26 × 10(-5)), receptor binding (P = 1.26 × 10(-5)), and cytokine activity (P = 2.01 × 10(-3)). Cellular component enrichment analysis revealed that the DEGs were significantly enriched in the plasma membrane (P = 1.91 × 10(-31)), an integral component of the membrane (P = 7.39 × 10(-13)), and extracellular region (P = 7.63 × 10(-11)). The KEGG pathway analysis showed that the DEGs were enriched in the cytokine-cytokine receptor interaction (P = 3.05 × 10(-17)), chemokine signaling (P = 3.50 × 10(-7)), T-cell receptor signaling (P = 5.17 × 10(-4)), and RA (P = 5.17 × 10(-4)) pathways. We confirmed that RA was correlated with the upregulation of the PPI network hub genes, such as CXCL13, CXCL6, CCR5, CXCR5, CCR2, CXCL3, and CXCL10, and the downregulation of the PPI network hub gene such as SSTR1. CONCLUSION: This study identified and validated the DEGs in the synovial tissue samples of patients with RA, which highlighted the activity of a subset of chemokine genes, thereby providing novel insights into the molecular mechanisms of RA pathogenesis and identifying potential diagnostic and therapeutic targets for RA. | |
| 34644522 | Reduced individual treatment delivery has no effect on outcomes in a multidisciplinary pai | 2022 Feb | Objective There is little information on how multidisciplinary pain management programs (MPMPs), the gold-standard treatment for people with chronic non-cancer pain, should be structured or delivered. This study compared outcomes from a 3-week in-patient MPMP between those who attended a group-based program that included 8 h of individual therapy each week and those who attended when the amount of individual therapy had been halved. Methods Participants were patients attending an MPMP with a large component of individual sessions (n  = 112; Standard) and patients attending the same MPMP after it switched to predominantly group-based sessions (n  = 117; Revised). The Hospital Anxiety and Depression Scale (HADS) and Queen Elizabeth (QE) Health Scale were administered to participants at baseline and discharge. Regression analysis was used to compare outcomes between the two delivery formats. Results There were no significant differences in any outcome measures between the two delivery formats overall. The QE Health Scale (P  < 0.001) and HADS depression (P  < 0.05) scores were significantly better for patients with rheumatoid arthritis or osteoarthritis who had undertaken the Revised program compared with the Standard program. Conclusions This study provides support that changing the amount of individual therapy within in-patient MPMPs does not change patient outcomes. However, there is evidence that those with rheumatoid arthritis and osteoarthritis respond better to a more group-based approach, suggesting that different populations may be suited to different delivery formats. What is known about the topic? Studies have shown mixed results as to whether group- or individual-based rehabilitation programs are more effective. Previous systematic reviews on physiotherapy- or psychological-based interventions have concluded that individual and group approaches are generally equivalent in terms of patient outcomes. MPMPs are trending towards more group-based delivery of content; however, it is unknown whether the equivalence of efficacy between group and individual formats extends to a chronic pain population receiving multidisciplinary care. What does this paper add? This research specifically adds to the knowledge that almost exclusive group delivery of therapy is just as effective as a program with more individual components in a population of patients participating in an MPMP. There is some evidence that those with rheumatoid arthritis and osteoarthritis in the almost exclusive group delivery program had better outcomes than those in the program with more individual components, indicating that specific conditions may benefit more from a group approach. What are the implications for practitioners? Practitioners can be confident that group delivery is just as effective as individual delivery of program components in an MPMP. Thus, decisions regarding the delivery format can be based on factors such as practical considerations, cost or patient and clinician preference. | |
| 34940957 | Baseline Anti-Citrullinated Protein Antibody Status and Response to Abatacept or Non-TNFi | 2022 Apr | INTRODUCTION: Patients with rheumatoid arthritis (RA) may respond to treatments differently based on their underlying serology and biomarker status, but real-world data comparing treatment responses to abatacept versus other non-TNFi biologic or targeted-synthetic DMARDs by anti-citrullinated protein antibody (ACPA) status remain limited. We assessed the association between ACPA status and response to treatment in patients with RA. METHODS: Adults from CorEvitas' RA Registry were identified who initiated abatacept, rituximab, tocilizumab, or tofacitinib, and had ACPA measured at/prior to treatment initiation and at the 6-month follow-up visit. Three cohorts were included: abatacept/rituximab (2006-2019), abatacept/tocilizumab (2010-2019), and abatacept/tofacitinib (2012-2019). Patient characteristics at initiation were compared by ACPA status (positive [+], anti-cyclic citrullinated peptide-2 [anti-CCP2] ≥ 20 U/ml; negative [-], anti-CCP2 < 20 U/ml). Outcomes over 6 months: changes in Clinical Disease Activity Index (CDAI), modified Health Assessment Questionnaire (mHAQ), patient global assessment (PGA) scores, and proportion of patients achieving a clinical response. Adjusted mean differences and odds ratios were estimated using mixed-effects linear regression models. RESULTS: Overall, 982 abatacept, 246 rituximab, 404 tocilizumab, and 429 tofacitinib initiators were identified. ACPA+ (vs. ACPA-) patients had longer disease duration and more erosive disease. During most time periods adjusted mean changes in CDAI, mHAQ, and PGA scores and the proportion of patients achieving a clinical response were significantly higher for ACPA+ versus ACPA- patients initiating abatacept. Adjusted mean change in PGA score and patient fatigue were significantly higher for ACPA+ versus ACPA- patients initiating rituximab. No significant differences were seen by ACPA status for patients initiating tocilizumab or tofacitinib. CONCLUSIONS: Patients who initiated abatacept or rituximab and were ACPA+ had a greater clinical response at 6-month follow-up post index compared to patients who were ACPA- treated with the same biologic. | |
| 35385180 | Spectrum of diseases associated with pyoderma gangrenosum and correlation with effectivene | 2022 May | Pyoderma gangrenosum (PG) has been linked to various underlying systemic diseases; many associations are based on case reports or small case series, including hidradenitis suppurativa. Literature examining systemic therapies according to underlying comorbid condition is limited. The study objective was to investigate comorbid diseases of PG and correlate disease associations with effectiveness of therapeutic interventions. Using Johns Hopkins Medical Institutions medical records, 220 patients had an ICD-9 code of 686.01 for PG between 1 January 2006 and 30 June 2015, of whom 130 patients met rigorous inclusion/exclusion criteria for PG (non-peristomal). The 130 PG patients in our study were 69% female, 58% Caucasian, and 35% African American. Documented comorbid conditions included inflammatory bowel disease (IBD; 35%), rheumatoid arthritis (RA; 12%), hidradenitis suppurativa (HS; 14%), and monoclonal gammopathy (12%). PG patients with HS versus without HS were more likely to be African-American (83% vs. 28%; P < 0.001) and had an earlier mean age of PG onset (38 vs. 48 years; P = 0.02). Strikingly, 53% of female African-American patients with PG onset prior to age 40 had comorbid HS. Comorbid inflammatory bowel disease was observed in 38% of PG patients with RA, 28% of PG patients with HS, and 27% of PG patients with monoclonal gammopathy. Of the 32 patients who received infliximab for active PG, complete ulcer healing was observed in 83% (5/6) of patients with comorbid HS versus 31% (8/26) of patients without HS (Fisher exact P = 0.03). Screening patients for associated systemic disease for multiple related illnesses is essential. Effectiveness of systemic therapy may depend upon the underlying systemic disease; hidradenitis suppurativa may be a specific example. | |
| 35177555 | CT-like images in MRI improve specificity of erosion detection in patients with hand arthr | 2022 Feb | OBJECTIVE: To compare the diagnostic accuracy of susceptibility-weighted imaging (SWI), standard T1-weighted (T1w) images and high-resolution 3D-gradient echo sequences (volumetric interpolated breath-hold examination (VIBE)) for detection of erosions in patients with peripheral arthritis using CT as standard of reference. MATERIALS AND METHODS: A total of 36 patients were included in the study. All patients underwent CT and MRI, including SWI, VIBE and T1w sequences of the clinically more affected hand. Two trained readers scored all imaging datasets separately for erosions in a blinded fashion. Specificity, sensitivity and diagnostic accuracy of MRI sequences were calculated on a per-patient level. RESULTS: CT was positive for erosion in 16 patients and 77 bones (Rheumatoid Arthritis MRI Score >0), T1w in 28 patients, VIBE in 25 patients and SWI in 17 patients. All MRI sequences performed with comparably high sensitivities (T1w 100%, VIBE 94% and SWI 94%). SWI had the highest specificity of 90%, followed by VIBE (50%) and T1w (40%). Both T1w and VIBE produced significantly higher sum scores than CT (341 and 331 vs 148, p<0.0001), while the sum score for SWI did not differ from CT (119 vs 148; p=0.411). CONCLUSION: Specificity for erosion detection remains a challenge for MRI when conventional and high-resolution sequences are used but can be improved by direct bone depiction with SWI. Both T1w and VIBE tend to overestimate erosions, when CT is used as the standard of reference. | |
| 35336746 | NF-κB Signaling and Inflammation-Drug Repurposing to Treat Inflammatory Disorders? | 2022 Feb 26 | NF-κB is a central mediator of inflammation, response to DNA damage and oxidative stress. As a result of its central role in so many important cellular processes, NF-κB dysregulation has been implicated in the pathology of important human diseases. NF-κB activation causes inappropriate inflammatory responses in diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS). Thus, modulation of NF-κB signaling is being widely investigated as an approach to treat chronic inflammatory diseases, autoimmunity and cancer. The emergence of COVID-19 in late 2019, the subsequent pandemic and the huge clinical burden of patients with life-threatening SARS-CoV-2 pneumonia led to a massive scramble to repurpose existing medicines to treat lung inflammation in a wide range of healthcare systems. These efforts continue and have proven to be controversial. Drug repurposing strategies are a promising alternative to de novo drug development, as they minimize drug development timelines and reduce the risk of failure due to unexpected side effects. Different experimental approaches have been applied to identify existing medicines which inhibit NF-κB that could be repurposed as anti-inflammatory drugs. | |
| 34558663 | Immunomodulatory functions of TRPM7 and its implications in autoimmune diseases. | 2022 Jan | An autoimmune disease is an inappropriate response to one's tissues due to a break in immune tolerance and exposure to self-antigens. It often leads to structural and functional damage to organs and systemic disorders. To date, there are no effective interventions to prevent the progression of autoimmune diseases. Hence, there is an urgent need for new treatment targets. TRPM7 is an enzyme-coupled, transient receptor ion channel of the subfamily M that plays a vital role in pathologic and physiologic conditions. While TRPM7 is constitutively activated under certain conditions, it can regulate cell migration, polarization, proliferation and cytokine secretion. However, a growing body of evidence highlights the critical role of TRPM7 in autoimmune diseases, including rheumatoid arthritis, multiple sclerosis and diabetes. Herein, we present (a) a review of the channel kinase properties of TRPM7 and its pharmacological properties, (b) discuss the role of TRPM7 in immune cells (neutrophils, macrophages, lymphocytes and mast cells) and its upstream immunoreactive substances, and (c) highlight TRPM7 as a potential therapeutic target for autoimmune diseases. | |
| 34379187 | Possible roles of anti-type II collagen antibody and innate immunity in the development an | 2022 Feb | The pathogenesis of both diabetic retinopathy (DR) and rheumatoid arthritis (RA) has recently been considered to involve autoimmunity. Serum and synovial fluid levels of anti-type II collagen antibodies increase early after the onset of RA, thus inducing immune responses and subsequent hydrarthrosis and angiogenesis, which resemble diabetic macular edema and proliferative DR (PDR), respectively. We previously reported that DR is also associated with increased serum levels of anti-type II collagen antibodies. Retinal hypoxia in DR may induce pericytes to express type II collagen, resulting in autoantibody production against type II collagen. As the result of blood-retinal barrier disruption, anti-type II collagen antibodies in the serum come into contact with type II collagen around the retinal vessels. A continued loss of pericytes and type II collagen around the retinal vessels may result in a shift of the immune reaction site from the retina to the vitreous. It has been reported that anti-inflammatory M2 macrophages increased in the vitreous of PDR patients, accompanied by the activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, a key regulator of innate immunity. M2 macrophages promote angiogenesis and fibrosis, which might be exacerbated and prolonged by dysregulated innate immunity. | |
| 35611061 | Specialized Pro-Resolving Mediators Do Not Inhibit the Synthesis of Inflammatory Mediators | 2022 May | BACKGROUND: Tumor necrosis factor (TNF)-α, a proinflammatory cytokine, is involved in the pathogenesis of rheumatoid arthritis (RA). The omega-3 unsaturated fatty acid-derived metabolites resolvin (Rv) D1, RvE1, and maresin-1 (MaR1) have been reported as anti-inflammatory lipid mediators and are known as specialized pro-resolving mediators (SPMs). In this study, we aimed to investigate the anti-inflammatory effects of SPMs on TNF-α-induced responses in synovial fibroblasts. METHODS: We investigated the effects of SPMs on gene expression and/or production of cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), interleukin (IL)-6, and matrix metalloproteinase (MMP)-3, which are involved in TNF-α-induced synovitis in RA or OA synovial fibroblasts, by quantitative real-time PCR. We also investigated the effects of SPMs on the mitogen-activated protein kinase (MAPK) signaling pathway by western blotting. Anti-inflammatory effects of SPMs were evaluated by applying SPMs to cultured synovial fibroblasts, followed by TNF-α stimulation. RESULTS: The induction of COX-2, mPGES-1, IL-6, and MMP-3 by TNF-α in synovial fibroblasts was not suppressed by omega 3-derived SPMs regardless of their origin such as RA or OA. SPMs had no effect on lipid mediator receptor gene expression induce by TNF-α and did not inhibit the TNF-α-activated MAPK signaling pathway. The production of COX-2 and IL-6 protein was significantly decreased by p38 inhibitor. CONCLUSION: Despite reports on the anti-inflammatory effect of omega 3-derived SPMs, its anti-inflammatory effect on TNF-α-induced responses was not observed in synovial fibroblasts. The reason may be that SPMs have no suppressive effect on p38 activation, which plays an important role in the production of inflammatory cytokines in synovial fibroblasts. |