Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
| ID | PMID | Title | PublicationDate | abstract |
|---|---|---|---|---|
| 32969552 | Clinical features in 305 patients with juvenile idiopathic arthritis: A single center Turk | 2021 Jun | BACKGROUND: Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatologic disease of childhood. The various subtypes of JIA differ in clinical features and treatments. The aim of this study was to analyze the frequency of JIA subtypes, patient demographic and clinical features, as well as the rates of macrophage activation syndrome, uveitis, and remission in Turkish JIA patients treated at a single center, and to compare the findings to those in the literature. METHODS: The files of all JIA patients treated at our pediatric rheumatology department between January 2017 and January 2019 were retrospectively reviewed. Patient demographic, clinical, and laboratory data were obtained from the patients' files and the hospital database. RESULTS: The study included 305 patients (180 females) with a mean age at onset of 7.83 ± 4.62 years. Among all the JIA subtypes, the most frequent was oligoarthritis (41.6%), followed by enthesitis-related arthritis (29.2%), rheumatoid factor (RF)-negative polyarthritis (13.4%), systemic arthritis (9.5%), RF-positive polyarthritis (2.6%), psoriatic arthritis (2.0%), and undifferentiated arthritis (1.6%). At the time of data collection, 278 patients (91.0%) were in remission, whereas 27 patients (9.0%) had active disease. Macrophage activation syndrome developed in 12 of the 29 (41.0%) systemic arthritis. Uveitis was noted in 32 (10.0%) patients. Biological agents were administered in 142 of the patients. CONCLUSIONS: The available data indicate that JIA as a whole is a heterogeneous disease with significant variability in course and long-term outcome. As such, each patient should be evaluated according to his / her disease subtype. | |
| 34313940 | Predicting presenteeism using measures of health status. | 2022 Feb | OBJECTIVES: To identify whether it is feasible to develop a mapping algorithm to predict presenteeism using multiattribute measures of health status. METHODS: Data were collected using a bespoke online survey in a purposive sample (n = 472) of working individuals with a self-reported diagnosis of Rheumatoid arthritis (RA). Survey respondents were recruited using an online panel company (ResearchNow). This study used data captured using two multiattribute measures of health status (EQ5D-5 level; SF6D) and a measure of presenteeism (WPAI, Work Productivity Activity Index). Statistical correlation between the WPAI and the two measures of health status (EQ5D-5 level; SF6D) was assessed using Spearman's rank correlation. Five regression models were estimated to quantify the relationship between WPAI and predict presenteeism using health status. The models were specified based in index and domain scores and included covariates (age; gender). Estimated and observed presenteeism were compared using tenfold cross-validation and evaluated using Root mean square error (RMSE). RESULTS: A strong and negative correlation was found between WPAI and: EQ5D-5 level and WPAI (r = - 0.64); SF6D (r =- 0.60). Two models, using ordinary least squares regression were identified as the best performing models specifying health status using: SF6D domains with age interacted with gender (RMSE = 1.7858); EQ5D-5 Level domains and age interacted with gender (RMSE = 1.7859). CONCLUSIONS: This study provides indicative evidence that two existing measures of health status (SF6D and EQ5D-5L) have a quantifiable relationship with a measure of presenteeism (WPAI) for an exemplar application of working individuals with RA. A future study should assess the external validity of the proposed mapping algorithms. | |
| 33826929 | Uveitis-related Factors in Patients With Spondyloarthritis: TReasure Real-Life Results. | 2021 Aug | PURPOSE: Spondyloarthritis (SpA) is a group of diseases with overlapping skeletal and extra-articular features. Acute anterior uveitis (AAU) is the most common extra-articular manifestation of SpA. The relation between AAU and SpA is well defined in the current literature. Our study aims to analyze the frequency and factors associated with AAU in different forms of SpA in a large nationwide cohort of Turkish SpA patients. DESIGN: Retrospective cohort study. METHODS: The data were obtained from the TReasure database, which compiles data from records of the web-based Rheumatoid Arthritis (RA) and SpA patients treated with biological disease-modifying anti-rheumatismal drugs from different regions of Turkey. The clinical characteristics of SpA and uveitis are recorded. RESULTS: Data of the 4,297 SpA patients were included in the study. Overall, 475 of 4,297 patients (11.0%) had experienced 1 or more episodes of uveitis. SpA patients with older age (P < .001), a smoking history (P = .004), delayed diagnosis (P = .001), longer disease duration (P < .001), arthritis (P < .001), positive HLA-B27 (P < .001), a family history of SpA (P < .001), and radiographic damage (presence of sacroiliitis, syndesmophytes, bamboo spine, hip involvement) (P < .001 for all) more commonly had uveitis. On the other hand, uveitis was less prevalent in patients with psoriasis and psoriatic arthritis (P < .001 for both). CONCLUSION: Uveitis may be the key feature leading to SpA diagnosis. Patients with radiographic damage and long disease duration have an increased risk for uveitis in both male and female SpA patients. Patients with uveitis should be referred to a rheumatologist for a thorough evaluation of SpA. | |
| 32100944 | Low Incidence of Inflammatory Bowel Disease Adverse Events in Adalimumab Clinical Trials A | 2021 Feb | OBJECTIVE: Adalimumab is approved for treatment of Crohn's disease and ulcerative colitis. Thus, we postulated that exacerbation or new-onset of inflammatory bowel disease (IBD) would be rare events in patients treated with adalimumab for non-IBD indications. The objective was to evaluate the incidence of IBD adverse events (AEs) across adalimumab trials. METHODS: IBD AE rates in 75 adalimumab clinical trials in rheumatoid arthritis, polyarticular juvenile idiopathic arthritis, pediatric enthesitis-related arthritis, uveitis, hidradenitis suppurativa, adult and pediatric psoriasis, psoriatic arthritis, nonpsoriatic arthritis peripheral spondyloarthritis (SpA), axial SpA, including nonradiographic axial SpA, and ankylosing spondylitis, were analyzed. Search terms for IBD AEs (new onset or worsening/flare) included IBD, ulcerative colitis, Crohn's disease, and ulcerative proctitis. RESULTS: This analysis included 24,114 patients, representing 36,508 patient-years of adalimumab exposure. The overall rate of IBD AEs in adalimumab-treated patients was 0.1 (95% confidence interval [95% CI] 0.1-0.2)/100 patient-years (41 events), ranging from no events (psoriatic arthritis, uveitis, and pediatric trials) to 0.8 (95% CI 0.2-2.2)/100 patient-years in peripheral SpA. The rate of IBD in axial SpA was 0.6 (95% CI 0.4-1.0)/100 patient-years. During placebo-controlled trials, the overall IBD rate was 0.1 (95% CI 0.0-0.3)/100 patient-years for adalimumab groups (3 events in 6,781 patients; 2,752 patient-years of exposure) and 0.1 (95% CI 0.0-0.4)/100 patient-years for placebo groups (1 event in 3,493 patients; 1,246 patient-years of exposure). IBD rates in axial SpA were 0.5 (95% CI 0.1-1.4)/100 patient-years for adalimumab and 0.6 (95% CI 0.0-3.1)/100 patient-years for placebo. CONCLUSION: The rates of IBD AEs in adalimumab clinical trials were generally low across the evaluated diseases, including axial SpA; all events occurred in adult patients. | |
| 33542048 | Methodological aspects of design, analysis and reporting of studies with work participatio | 2021 Feb | OBJECTIVE: To summarise the methodological aspects in studies with work participation (WP) as outcome domain in inflammatory arthritis (IA) and other chronic diseases. METHODS: Two systematic literature reviews (SLRs) were conducted in key electronic databases (2014-2019): search 1 focused on longitudinal prospective studies in IA and search 2 on SLRs in other chronic diseases. Two reviewers independently identified eligible studies and extracted data covering pre-defined methodological areas. RESULTS: In total, 58 studies in IA (22 randomised controlled trials, 36 longitudinal observational studies) and 24 SLRs in other chronic diseases were included. WP was the primary outcome in 26/58 (45%) studies. The methodological aspects least accounted for in IA studies were as follows (proportions of studies positively adhering to the topic are shown): aligning the studied population (16/58 (28%)) and sample size calculation (8/58 (14%)) with the work-related study objective; attribution of WP to overall health (28/58 (48%)); accounting for skewness of presenteeism/sick leave (10/52 (19%)); accounting for work-related contextual factors (25/58 (43%)); reporting attrition and its reasons (1/58 (2%)); reporting both aggregated results and proportions of individuals reaching predefined meaningful change or state (11/58 (16%)). SLRs in other chronic diseases confirmed heterogeneity and methodological flaws identified in IA studies without identifying new issues. CONCLUSION: High methodological heterogeneity was observed in studies with WP as outcome domain. Consensus around various methodological aspects specific to WP studies is needed to improve quality of future studies. This review informs the EULAR Points to Consider for conducting and reporting studies with WP as an outcome in IA. | |
| 34710848 | Deficiency of β-arrestin2 alleviates apoptosis through GRP78-ATF6-CHOP signaling pathway | 2021 Dec | The etiology of primary Sjögren's syndrome (pSS) remains unknown, and there is no ideal drug for the specific treatment of pSS. β-arrestin2 is a key protein that mediates desensitization and internalization of G protein-coupled receptors (GPCRs) and it participates in inflammatory and immune responses that have been found to mediate apoptosis in autoimmune disease. In this study, we established an experimental Sjögren's syndrome (ESS) mouse model to elucidate the molecular mechanisms of β-arrestin2 in pSS. First, excessive activation of β-arrestin2 and GRP78-ATF6-CHOP apoptosis signaling were detected in specimens from pSS patients. In vivo, we found that inhibition of GRP78-ATF6-CHOP apoptosis signaling improved ESS symptoms, and the targeted deletion of β-arrestin2 significantly increased saliva flow, alleviated salivary gland indices, and improved tissue integrity in the ESS model by downregulating GRP78-ATF6-CHOP apoptosis signaling. In vitro, we used IFNα to stimulate human salivary gland epithelial cells (HSGECs), and the results showed that IFNα activated GRP78-ATF6-CHOP apoptosis signaling, decreased cell viability, and induced apoptosis, which were negatively regulated by the ERS inhibitor 4-PBA. In addition, β-arrestin2 depletion downregulated GRP78-ATF6-CHOP apoptosis signaling to alleviate cell apoptosis, and the effect depended on the interaction between GRP78 and β-arrestin2. In summary, our results suggest that excessive activation of GRP78-ATF6-CHOP apoptosis signaling is involved in the pathogenesis of pSS and that β-arrestin2 encourages inflammation-induced epithelial apoptosis through GRP78-ATF6-CHOP apoptosis signaling. This research further clarified the underlying role of β-arrestin2 and provided an experimental foundation for β-arrestin2 depletion in the treatment of the human autoimmune disorder pSS. | |
| 33179091 | Mesenchymal stem cells negatively regulate CD4+ T cell activation in patients w | 2021 Jan | Treatment with mesenchymal stem cells (MSCs) has been revealed to suppress CD4+ T cells and autoimmunity in both mouse models and patients with primary Sjögren syndrome (pSS); however, the underlying mechanism remains unclear. MicroRNAs (miRNAs or miRs) mediate CD4+ T cell activation, but the mechanism is not understood, particularly for CD4+ T cells treated with MSCs. Characterization of miRNAs may reveal pSS pathogenesis, guide MSC treatment and provide more personalized management options. The present study aimed to perform an miRNome analysis of quiescent and T cell receptor (TCR)‑activated CD4+ T cells treated with MSCs via miRNA proï¬les and bioinformatics. Following 72 h of co‑culture, MSCs inhibited TCR‑induced CD4+ T cell activation and decreased IFN‑γ levels. The numbers of aberrant miRNAs in pSS naïve (vs. healthy naïve), pSS activation (vs. pSS naïve), MSC treatment and pre‑IFN‑γ MSC treatment (vs. pSS activation) groups were 42, 55, 27 and 32, respectively. Gene enrichment analysis revealed that 259 pathways were associated with CD4+ T cell stimulation, and 240 pathways were associated with MSC treatment. Increased miRNA‑7150 and miRNA‑5096 and decreased miRNA‑125b‑5p and miRNA‑22‑3p levels in activated CD4+ T cells from patients with pSS were reversed by MSC treatment. Notably, the proliferation of CD4+ T cells and CD4+ IFN‑γ+ cells, expression levels of miRNA‑125b‑5p and miRNA‑155 in CD4+ T cells and supernatant IFN‑γ secretion were associated with disease activity. miRNA may play a vital role in MSC treatment for activated CD4+ T cells. The results indicated that the expression levels of miRNA‑125b‑5p and miRNA‑155 in TCR‑activated CD4+ T cells from patients with pSS may provide insight regarding autoimmune diseases and offer a novel target for prospective treatment. Therefore, these results may be crucial in providing MSC treatment for pSS. | |
| 33707430 | Salivary dysbiosis in Sjögren's syndrome and a commensal-mediated immunomodulatory effect | 2021 Mar 11 | Salivary gland epithelial cells (SGECs) have been implicated in the pathogenesis of Sjögren's syndrome due to aberrant antigen-presentation function. This study examined the hypothesis that oral dysbiosis modulates the antigen-presentation function of SGECs, which regulates CD4 T cell proliferation in primary Sjögren's syndrome (pSS). Saliva samples from 8 pSS patients and 16 healthy subjects were analyzed for bacterial 16S ribosomal DNA. As a result, 39 differentially abundant taxa were identified. Among them, the phylum Proteobacteria comprised 21 taxa, and this phylum was mostly enriched in the healthy controls. The proteobacterium Haemophilus parainfluenzae was enriched in the healthy controls, with the greatest effect size at the species level. Treatment of A253 cells in vitro with H. parainfluenzae upregulated PD-L1 expression, and H. parainfluenzae-pretreated A253 cells suppressed CD4 T cell proliferation. The suppression was partially reversed by PD-L1 blockade. Among low-grade xerostomia patients, salivary abundance of H. parainfluenzae decreased in pSS patients compared to that in non-pSS sicca patients. Our findings suggest that H. parainfluenzae may be an immunomodulatory commensal bacterium in pSS. | |
| 32940706 | Ultrasound-guided core needle biopsy compared with open biopsy: a new diagnostic approach | 2021 Mar 2 | OBJECTIVE: Persistent (≥2 months) major salivary gland enlargement in primary SS (pSS) patients is a well-known sign of possible involvement by B cell lymphoma. The study aimed to evaluate the diagnostic accuracy and safety of US-guided core needle biopsy (CNB) of major salivary glands compared with open surgical biopsy. METHODS: Prospective pSS patients (cases) with clinically persistent salivary gland enlargement underwent US-guided CNB and were compared with retrospective pSS patients (controls) submitted to open surgical biopsy. The features analysed were pre-biopsy clinical and laboratory findings, adequacy of the material for histology and diagnostic-rendered and biopsy-related complications (reported by the patient with a questionnaire and clinically verified). RESULTS: Thirteen cases underwent US-guided CNB: in nine, biopsy was performed on the parotid gland and in four it was performed on the submandibular gland. Sufficient material was obtained for pathological diagnosis in all samples. The final diagnoses were 5 (38.5%) B cell lymphoma, 1 (7.7%) lymphoepithelial sialadenitis, 4 (30.7%) other sialadenitis (granulomatous consistent with sarcoidosis, IgG4-related disease, chronic sclerosing, diffuse chronic) and 3/13 (23.1%) miscellaneous lesions. Thirteen controls underwent open surgical biopsy of the parotid. In one, inadequate material was obtained, while in 12 (92.3%) the pathologic diagnoses were 4 (33.3%) B cell lymphoma, 2 (16.7%) lymphoepithelial sialadenitis, 4 (33.3%) uncertain lymphoproliferative lesions and 2 (16.7%) miscellaneous lesions. Six cases (46.1%) reported six transient complications and 12/13 (92.3%) controls had 2 persistent and 14 transient complications. CONCLUSION: US-guided CNB represents a novel, clinically relevant and safe approach for the management of pSS patients with parotid or submandibular persistent enlargement. | |
| 34288018 | The immunosuppressive activity of artemisinin-type drugs towards inflammatory and autoimmu | 2021 Nov | The sesquiterpene lactone artemisinin from Artemisia annua L. is well established for malaria therapy, but its bioactivity spectrum is much broader. In this review, we give a comprehensive and timely overview of the literature regarding the immunosuppressive activity of artemisinin-type compounds toward inflammatory and autoimmune diseases. Numerous receptor-coupled signaling pathways are inhibited by artemisinins, including the receptors for interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α), β3-integrin, or RANKL, toll-like receptors and growth factor receptors. Among the receptor-coupled signal transducers are extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), AKT serine/threonine kinase (AKT), mitogen-activated protein kinase (MAPK)/extracellular signal regulated kinase (ERK) kinase (MEK), phospholipase C γ1 (PLCγ), and others. All these receptors and signal transduction molecules are known to contribute to the inhibition of the transcription factor nuclear factor κ B (NF-κB). Artemisinins may inhibit NF-κB by silencing these upstream pathways and/or by direct binding to NF-κB. Numerous NF-κB-regulated downstream genes are downregulated by artemisinin and its derivatives, for example, cytokines, chemokines, and immune receptors, which regulate immune cell differentiation, apoptosis genes, proliferation-regulating genes, signal transducers, and genes involved in antioxidant stress response. In addition to the prominent role of NF-κB, other transcription factors are also inhibited by artemisinins (mammalian target of rapamycin [mTOR], activating protein 1 [AP1]/FBJ murine osteosarcoma viral oncogene homologue [FOS]/JUN oncogenic transcription factor [JUN]), hypoxia-induced factor 1α (HIF-1α), nuclear factor of activated T cells c1 (NF-ATC1), Signal transducers and activators of transcription (STAT), NF E2-related factor-2 (NRF-2), retinoic-acid-receptor-related orphan nuclear receptor γ (ROR-γt), and forkhead box P-3 (FOXP-3). Many in vivo experiments in disease-relevant animal models demonstrate therapeutic efficacy of artemisinin-type drugs against rheumatic diseases (rheumatoid arthritis, osteoarthritis, lupus erythematosus, arthrosis, and gout), lung diseases (asthma, acute lung injury, and pulmonary fibrosis), neurological diseases (autoimmune encephalitis, Alzheimer's disease, and myasthenia gravis), skin diseases (dermatitis, rosacea, and psoriasis), inflammatory bowel disease, and other inflammatory and autoimmune diseases. Randomized clinical trials should be conducted in the future to translate the plethora of preclinical results into clinical practice. | |
| 33485983 | A hybrid platform featuring nanomagnetic ligand fishing for discovering COX-2 selective in | 2021 May 10 | ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea laniceps Hand.-Mazz. (Compositae) is a representative "snow lotus" herb well known in Chinese folk medicine to treat inflammation-related diseases such as arthritis. S. laniceps (SL) shows anti-inflammatory and analgesic potencies and contains various constituents potentially with cyclooxygenase-2 (COX-2) selective inhibition. The herb is a valuable source of natural alternatives to synthetic COX-2 selective nonsteroidal anti-inflammatory drugs, a common medication for rheumatoid arthritis (RA) and osteoarthritis (OA) reported with serious cardiovascular side effects. AIM OF THE STUDY: Based on an innovative drug screening platform, this study aimed to discover safe, effective COX-2 selective inhibitors from SL. MATERIALS AND METHODS: An enzyme-anchored nanomagnetic fishing assay was developed to separate COX-2 ligands from SL. Cell and animal models of cardiomyocytes, lipopolysaccharide-stimulated macrophages, rat adjuvant-induced arthritis, and anterior cruciate ligament transection-induced OA rats, were adopted to screen the single/combined ligands regarding toxicity and bioactivity levels. Molecular docking was employed to unravel binding mechanisms of the ligands towards COX-1 and COX-2. RESULTS: Four COX-2 selective compounds were separated from SL using optimized COX-2-functionalized magnetic nanoparticles. All the four ligands were proved with evidently lower cardiotoxicity both in vitro and in vivo than celecoxib, a known COX-2 selective inhibitor. Two ligands, scopoletin and syringin, exhibited potent anti-arthritic activities in rat models of RA and OA by alleviating clinical statuses, immune responses, and joint pathological features; their optimum combination ratio was discovered with stronger remedial effects on rat OA than single administrations. The COX-1/2 binding modes of the two phytochemicals contributed to explain their cardiac safety and therapeutic performances. CONCLUSIONS: The screened chemicals are promising to be developed as COX-2 selective inhibitors as part of treating RA and OA. The hybrid strategy for discovering therapeutic agents from SL is shown here to be efficient; it should be equally valuable for finding other active chemicals in other natural sources. | |
| 33812608 | Strontium ranelate-laden near-infrared photothermal-inspired methylcellulose hydrogel for | 2021 Apr | Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment. | |
| 33686279 | TNF in the era of immune checkpoint inhibitors: friend or foe? | 2021 Apr | Immune checkpoint inhibitors (ICIs) are effective in the treatment of patients with advanced cancer and have emerged as a pillar of standard cancer care. However, their use is complicated by adverse effects known as immune-related adverse events (irAEs), including ICI-induced inflammatory arthritis. ICI-induced inflammatory arthritis is distinguished from other irAEs by its persistence and requirement for long-term treatment. TNF inhibitors are commonly used to treat inflammatory diseases such as rheumatoid arthritis, spondyloarthropathies and inflammatory bowel disease, and have also been adopted as second-line agents to treat irAEs refractory to glucocorticoid treatment. Experiencing an irAE is associated with a better antitumour response after ICI treatment. However, whether TNF inhibition can be safely used to treat irAEs without promoting cancer progression, either by compromising ICI therapy efficacy or via another route, remains an open question. In this Review, we discuss clinical and preclinical studies that address the relationship between TNF, TNF inhibition and cancer. The bulk of the evidence suggests that at least short courses of TNF inhibitors are safe for the treatment of irAEs in patients with cancer undergoing ICI therapy. Data from preclinical studies hint that TNF inhibition might augment the antitumour effect of ICI therapy while simultaneously ameliorating irAEs. | |
| 34471964 | Radiographic changes in the distal ulna in non-rheumatoid patients with extensor digitorum | 2022 Feb | INTRODUCTION: Osteoarthritis of the distal radioulnar joint (DRUJ) is relatively common in elderly people. Extensor digitorum communis (EDC) ruptures occasionally and occurs with or without prior signs in these people. The purpose of this study was to clarify the radiographic changes in the distal ulna associated with EDC rupture. MATERIALS AND METHODS: We analyzed plain radiographs of 71 patients with non-rheumatoid arthritis and 40 controls. Radiographic changes in the distal ulna were categorized into normal, osteoarthritic-change (OA-change), and taper. We measured the ulnar variance (UV) and ulnar bowing angle in the posteroanterior radiographs and the dorsal bowing angle (DBA) and dorsal protrusion (DP) in the lateral radiographs. The shape of the sigmoid notch (SN) was categorized into flat, radial inclination, and dimple. The primary outcome was a comparison of radiographic parameters between the patient and the control groups. The secondary outcome was an analysis of the type of SN to investigate factors affecting ulnar deformation. RESULTS: The ratio of the radiographic change in the ulna, UV, DBA, and DP was significantly larger in the patient group than in the control group. Patients with the radial inclination type of SN showed a greater UV than those with the dimple type. CONCLUSIONS: Deformation of the distal ulna, a large UV, dorsal penetration, and dorsal bowing was related to EDC rupture. Regarding the large UV, the lunate shaved the upper half of the distal ulna, whereas the DRUJ shaved the lower half. These processes formed a tapered ulna head. A large UV and an inclination of the DRUJ played a role in ulnar head deformation. | |
| 33200729 | Autoantibody profile in eosinophilic granulomatosis and polyangiitis: predominance of anti | 2021 Mar | OBJECTIVES: To evaluate the autoantibody profile in eosinophilic granulomatosis and polyangiitis (EGPA) patients. METHODS: 33 EGPA patients were tested for anti-neutrophil cytoplasmic antibodies (ANCA), antinuclear antibodies (ANA), rheumatoid factor (RF), anti-alpha-enolase antibodies, and anti-eosinophil peroxidase (EPO) antibodies. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), hypereosinophilic syndrome (HES), rheumatoid arthritis (RA), primary biliary cirrhosis (PBC) patients and healthy subjects were tested as a control group. RESULTS: Anti-alpha-enolase antibodies were positive in 82% of EGPA patients at high titers. Although a high sensitivity was shown for an anti-alpha-enolase antibody titer above 1/100 (82%), the specificity for EGPA remained low (44%) (AUC=0.653, p=0.008). Anti-alpha-enolase antibodies predominated in males with EGPA (p=0.048) and were associated with skin involvement (p=0.040). Most of the EGPA patients positive for anti-alpha enolase antibodies (20 out of 27) had a negative indirect immunofluorescence test (IFT) for ANCA. ANCA were positive in 8 EGPA patients (24%) with a perinuclear pattern in all but one patient. The ANCA-target antigen was myeloperoxidase (MPO) and/or alpha-enolase. A usually fine-speckled ANA pattern was observed in 42% of the EGPA patients. RF was positive in 1 (6%) of the 18 EGPA patients tested. There was no association between the presence and levels of autoantibodies and EGPA disease activity. None of the patients and controls was positive for anti-EPO antibodies. CONCLUSIONS: Alpha-enolase may be a target of autoimmunity in EGPA patients and shows usually negative ANCA IFT results. | |
| 34667759 | Autoimmune Diseases, End Organ Dysfunction and Adverse Drug Reaction Following Drug Reacti | 2021 Sep | CONTEXT: Autoimmune diseases, organ dysfunction and new drug allergies are mentioned as long-term complications after DRESS. There is scarcity of data on this from the country. AIMS: To determine the frequency of autoimmune diseases, organ dysfunction, and new drug allergies after the resolution of DRESS. SETTINGS AND DESIGN: This retrospective cohort study was carried out among patients who received treatment for DRESS in a tertiary referral center. MATERIALS AND METHODS: In this retrospective cohort study, DRESS patients who received inpatient care in the dermatology department of our tertiary referral center from August 2014 to February 2017 were included. We excluded patients aged 12 years or below and those who had not completed minimum two years after the resolution of DRESS as on December 2019. We collected information on new onset autoimmune disease, end organ damage and new drug allergies detected after the resolution of DRESS through a telephonic interview. Those who consented were evaluated in our department. RESULTS: We could contact 40/50 (80%) identified individuals and all of them consented for telephonic interview. 17 patients gave consent for revaluation in our department. There were 22 females and 18 males. 17 had definite and 23 had probable DRESS. The frequency of detection of a new disease and a new drug allergy after DRESS was 10% (4/40) and 7.5% (3/40), respectively. We noted three (7.5%) autoimmune diseases (rheumatoid arthritis 1, alopecia areata 1, chronic autoimmune urticaria 1) and one end organ damage (chronic kidney disease) among the study participants. LIMITATIONS: Small sample size and retrospective study design were the limitations. CONCLUSIONS: Prospective studies with large sample size are needed to delineate the link between DRESS and autoimmunity, end organ damage, and new drug allergies. | |
| 34507492 | IMMUNE-MEDIATED INTRAOCULAR INFLAMMATION. A REVIEW. | 2021 Spring | Immune mediated inflammatory diseases are categorized into autoimmune and autoinflammatory. Autoimmune etiology is represented by autoreactive lymphocytes or autoantibodies, e.g. primary Sjögrens syndrome or rheumatoid arthritis. Ocular specific diseases with presumed autoimmune origin are sympathetic ophthalmia or birdshot chorioretinopathy. Autoinflammatory diseases are caused by mutations in regulatory genes for specific immunity. Hereditary periodic fevers represent monogenic autoinflammatory diseases; eye specific is Blau syndrome also named sarcoidosis with early onset. This article reviews the actual knowledge about immune mediated uveitides, their immunological mechanisms and the possible trigger role of infection in autoimmune inflammation. Immune privilege provides a protection of the eye against any strong immune reaction to foreign antigen, based on physical, immune, humoral and molecular mechanisms. Antigens hidden within the eye are revealed in case of damage of hematoretinal barrier caused by infection or mechanical insult. These ocular antigens have not been set as tolerable during the development and immune reaction is initiated subsequently. Current studies demonstrate that uveogenic trigger might be generated by own microbiome, particularly when dysregulated, so called dysbiosis. There is a known association between idiopathic inflammatory bowel disease with ankylosing spondylitis and anterior uveitis in humans. Intensive research is focused on microbiome and immune mediated inflammatory disease to influence therapeutically the intestinal microbiome. The animal models are used to study the immunopathological mechanisms of uveitis and the new therapeutic strategies, because of relatively low incidence of immune mediated uveitis in humans. | |
| 34402649 | Host-Microbe Metagenomics: a Lens To Refocus Our Perspective on Infectious and Inflammator | 2021 Aug 31 | A dynamic relationship involving pathogen, host immune response, and microbiome characterizes the biological framework of many infectious and inflammatory diseases. Combined host/microbe metagenomics (mNGS) enables simultaneous assessment of all three features, enabling the study and diagnosis of diverse infectious and inflammatory processes ranging from pneumonia to sepsis to inflammatory diseases such as rheumatoid arthritis. Host/microbe mNGS holds promise for new mechanistic insights, diagnostic approaches, and precision medicine interventions. | |
| 34381949 | COVID19 pneumonia with cavitation and cystic lung changes: multi-detector computed tomogra | 2021 | The COVID19 pandemic since its beginning in March 2020, continues to wreak havoc causing great morbidity and mortality with each passing day. Ample literature is now available describing the imaging features of COVID19 infection; however, there is still a paucity of knowledge on the various causes of pulmonary cavitation and cystic lesions which can be associated with the virus albeit uncommonly. Cavitation in a COVID19 positive patient could be a consequence of the infection itself or a manifestation of sinister etiologies like coinfection with bacterial, fungal or mycobacterial pathogens, or incidental malignancy/metastasis. It could also be a result of multiple cavitating pulmonary nodules as a manifestation of septic emboli and infarct, Granulomatosis with polyangiitis or rheumatoid arthritis creating a diagnostic dilemma. Similarly, the causes of cystic air spaces on chest CT in COVID19 patient can be varied, either primarily due to the infection itself or secondary to coexistent cystic bronchiectasis, emphysema, interstitial lung disease or mechanical ventilation-associated barotrauma as well as complicated pulmonary cysts. Through this pictorial review, we aim to highlight these uncommon imaging manifestations of COVID19 and educate the reader regarding the various causes, MDCT features and differentials to be considered while approaching a cavity/cystic lesion amidst this pandemic. | |
| 34340528 | The role of TGF-β2 in cartilage development and diseases. | 2021 Aug | Transforming growth factor-beta2 (TGF-β2) is recognized as a versatile cytokine that plays a vital role in regulation of joint development, homeostasis, and diseases, but its role as a biological mechanism is understood far less than that of its counterpart, TGF-β1. Cartilage as a load-resisting structure in vertebrates however displays a fragile performance when any tissue disturbance occurs, due to its lack of blood vessels, nerves, and lymphatics. Recent reports have indicated that TGF-β2 is involved in the physiological processes of chondrocytes such as proliferation, differentiation, migration, and apoptosis, and the pathological progress of cartilage such as osteoarthritis (OA) and rheumatoid arthritis (RA). TGF-β2 also shows its potent capacity in the repair of cartilage defects by recruiting autologous mesenchymal stem cells and promoting secretion of other growth factor clusters. In addition, some pioneering studies have already considered it as a potential target in the treatment of OA and RA. This article aims to summarize the current progress of TGF-β2 in cartilage development and diseases, which might provide new cues for remodelling of cartilage defect and intervention of cartilage diseases. |