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ID PMID Title PublicationDate abstract
34455948 A Systematic Review and Meta-Analysis of the Safety of Hydroxychloroquine in a Randomized 2022 INTRODUCTION: Hydroxychloroquine (HCQ) has recently become the focus of attention in the current COVID-19 pandemic. With an increase in the off-label use of HCQ, concern for the safety of HCQ has been raised. We, therefore, performed this systematic review to analyze the safety data of HCQ against placebo and active treatment in various disease conditions. METHODS: We searched PubMed, Embase, and Cochrane for Randomized Controlled Trials (RCTs) and Observational Studies (OSs) that evaluated HCQ for the treatment of any disease other than COVID19 in adult patients up to May 2020. We assessed the quality of the included studies using Risk of Bias 2 (for RCTs) and Newcastle-Ottawa Scale (for OSs). Data were analyzed with randomeffect meta-analysis. Sensitivity and subgroup analyses were performed to identify heterogeneity. RESULTS: A total of 6641 studies were screened, and 49 studies (40 RCTs and 9 OSs) with a total sample size of 35044 patients were included. The use of HCQ was associated with higher risks of TDAEs as compared to placebo/no active treatment [RR 1.47, 95%CI 1.03-2.08]. When HCQ was compared with active treatments, the risks of AEs [RR 0.74, 95% CI 0.63-0.86] and TDAEs were less in the HCQ arm [RR 0.57, 95% CI 0.39-0.81]. The outcomes did not differ in the sensitivity analysis. CONCLUSION: The results suggest that the use of HCQ was associated with a lower risk of AEs and TDAEs as compared to active treatment, whereas posing higher risk of TDAEs as compared to placebo.
34731348 Clinical joints manifestations in patients with psoriatic arthritis on musculoskeletal ult 2022 Apr OBJECTIVE: To investigate the clinical joints manifestations under musculoskeletal ultrasound (MSUS) and hematological findings in patients with psoriatic arthritis (PsA), which may provide a basis for improving the early diagnosis of PsA. METHODS: From September 2016 to February 2021, 328 patients with psoriasis visited the dermatological and rheumatic outpatient of the Beijing Friendship Hospital were enrolled in this retrospective study. Patients were enrolled according to a paired-design method. The PsA group included 164 patients diagnosed with PsA, and the control group included 164 patients diagnosed with psoriasis without PsA. Both groups of patients were evaluated by a rheumatoid immunologist, a dermatologist, and a sonographer. Demographic data, course of disease, severity of skin lesions, combined diseases, and previous treatment were all collected. All patients received MSUS and blood examinations. Lower extremity enthsis diseases were evaluated by Glasgow ultrasound enthesitis scoring system (GUESS). RESULTS: In the comparison of baseline clinical characteristics, the PsA group has longer course of psoriasis (P = 0.005), longer course of joints pain (P = 0.035), higher incidence of peripheral joints pain (P = 0.001), higher GUESS score (P < 0.001), and higher incidence of involved nails or toenails (P = 0.036) The most common joints involved were proximal interphalangeal joint (33.5%), knee (27.4%), and metacarpophalangeal joint (25.0%). Differences in clinical manifestations at different lower limb enthesitis on MSUS have also been proved. The positive incidences of rheumatoid factor (RF) (P = 0.002) and anti-cyclic citrullinated peptide (CCP) antibody (P < 0.001) in the PsA group were significantly higher than those in the control group. Binary Logistic regression showed that patients with anti-CCP antibody positive had a higher risk of active PsA compared to patients with negative antibodies in PsA group (OR: 0.626, 95%CI: 0.361-0.792, P < 0.05). CONCLUSION: In conclusion, the most common joints involved were proximal interphalangeal joint, knee, and metacarpophalangeal joint in patients with PsA, and the common types of diseased joints manifestations on MSUS were synovial thickening, fluid accumulation, bone destruction, increased blood flow signals, and attachment site inflammation. GUESS scoring systems can be used to identify PsA in patients with psoriasis. Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA. KEY POINTS: • GUESS scoring systems can be used to identify PsA in patients with psoriasis. • Psoriasis patients with RF and anti-CCP antibody positive were more likely to develop PsA, and anti-CCP antibody positive was a risk factor for active PsA.
35288653 IL-34 and protein-tyrosine phosphatase receptor type-zeta-dependent mechanisms limit arthr 2022 Mar 14 Myeloid cell mediated mechanisms regulate synovial joint inflammation. IL-34, a macrophage (Mø) growth and differentiation molecule, is markedly expressed in neutrophil and Mø-rich arthritic synovium. IL-34 engages a newly identified independent receptor, protein-tyrosine phosphatase, receptor-type, zeta (PTPRZ), that we find is expressed by Mø. As IL-34 is prominent in rheumatoid arthritis, we probed for the IL-34 and PTPRZ-dependent myeloid cell mediated mechanisms central to arthritis using genetic deficient mice in K/BxN serum-transfer arthritis. Unanticipatedly, we now report that IL-34 and PTPRZ limited arthritis as intra-synovial pathology and bone erosion were more severe in IL-34 and PTPRZ KO mice during induced arthritis. We found that IL-34 and PTPRZ: (i) were elevated, bind, and induce downstream signaling within the synovium in arthritic mice and (ii) were upregulated in the serum and track with disease activity in rheumatoid arthritis patients. Mechanistically, IL-34 and PTPRZ skewed Mø toward a reparative phenotype, and enhanced Mø clearance of apoptotic neutrophils, thereby decreasing neutrophil recruitment and intra-synovial neutrophil extracellular traps. With fewer neutrophils and neutrophil extracellular traps in the synovium, destructive inflammation was restricted, and joint pathology and bone erosion diminished. These novel findings suggest that IL-34 and PTPRZ-dependent mechanisms in the inflamed synovium limit, rather than promote, inflammatory arthritis.
34987201 Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach. 2022 Mar The four Janus kinase (JAK) proteins and seven signal transducer and activator of transcription (STAT) transcription factors mediate intracellular signal transduction downstream of cytokine receptors, which are implicated in the pathology of autoimmune, allergic and inflammatory diseases. Development of targeted small-molecule therapies such as JAK inhibitors, which have varied selective inhibitory profiles, has enabled a paradigm shift in the treatment of diverse disorders. JAK inhibitors suppress intracellular signalling mediated by multiple cytokines involved in the pathological processes of rheumatoid arthritis and many other immune and inflammatory diseases, and therefore have the capacity to target multiple aspects of those diseases. In addition to rheumatoid arthritis, JAK inhibition has potential for treatment of autoimmune diseases including systemic lupus erythematosus, spondyloarthritis, inflammatory bowel disease and alopecia areata, in which stimulation of innate immunity activates adaptive immunity, leading to generation of autoreactive T cells and activation and differentiation of B cells. JAK inhibitors are also effective in the treatment of allergic disorders, such as atopic dermatitis, and can even be used for the COVID-19-related cytokine storm. Mechanism-based treatments targeting JAK-STAT pathways have the potential to provide positive outcomes by minimizing the use of glucocorticoids and/or non-specific immunosuppressants in the treatment of systemic immune-mediated inflammatory diseases.
35620185 COVID-19-induced psoriatic arthritis: a case report. 2022 Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which may lead to uncontrolled immune activation and cytokine response in some. The pattern of pro-inflammatory cytokines is similar to that which has been observed to be involved in rheumatic diseases and target treatments. Viral arthritis is common with a wide variety in spectrum ranging from arthralgia to spurious and chronic arthritis. However, recent studies have demonstrated a correlation with endemic coronaviruses and increased risk of developing rheumatoid arthritis (RA). Cases are being identified that describe a post-COVID reactive; however, to date, no report has been published describing the onset of psoriasis and concomitant development of psoriatic arthritis after COVID-19 infection. We report an interesting case of psoriatic arthritis in a post-COVID-19 infection patient with review of the current literature.
32644671 Cartilage Graft. 2022 Jan Joint pain is a complex problem facing medical practitioners that has its origin in a host of conditions, injuries, and diseases. Between 2013 and 2015 alone, an estimated 54.4 million United States (US) adults (22.7%) annually were told by a doctor that they had some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia.  Physicians, researchers, and other medical providers have, for centuries, sought to understand the etiology and causes of joint pain in an effort to develop effective treatments to alleviate discomfort. Joint pain and/or arthritis is one of the most prevalent and expensive conditions known to humankind. In 2013, the American national medical costs attributable to arthritis were $140 billion. Additionally, with the aging population of most countries, the cost of treating arthritis is expected to double if not triple in the next several decades. As such, the need to find effective treatments, both medical and surgical, for the loss of articular cartilage is both important and financially imperative. The human knee is perhaps the most common joint to suffer the effects of articular cartilage loss. In a population of patients greater than 45-years-old, the age-standardized prevalence of radiographic osteoarthritis (OA) of the knee was reported to be between 19.2% (Framingham Study) to 27.8% (Johnston County Osteoarthritis Project). Additionally, in the Third National Health and Nutrition Examination Survey (NHANES III), nearly 37% of participants age 60 years or older had radiographic evidence of knee osteoarthritis. Thus, much attention has been turned to finding an effective method whereby the damaged or deficient articular hyaline cartilage can be restored to the knee. One method of surgically restoring a viable articular surface to the knee joint whose hyaline cartilage surface has been injured is through osteochondral allograft transplantation. Osteochondral allograft transplantation is an effective treatment when the source of knee pain is a large chondral defect or in the cases of post-traumatic arthritis. Ultimately, osteochondral allograft transplantation involves transferring allograft articular cartilage and subchondral bone that is appropriately size-matched to fill chondral defects with matured hyaline cartilage. Were one to describe this technique in a commonly understood metaphor, it would simulate the repair of a pot or chuckhole in the street by size match insertion of transplanted asphalt along with its attached subsurface roadbed into the defect.
35482925 Chronic inflammatory arthritis drives systemic changes in circadian energy metabolism. 2022 May 3 Chronic inflammation underpins many human diseases. Morbidity and mortality associated with chronic inflammation are often mediated through metabolic dysfunction. Inflammatory and metabolic processes vary through circadian time, suggesting an important temporal crosstalk between these systems. Using an established mouse model of rheumatoid arthritis, we show that chronic inflammatory arthritis results in rhythmic joint inflammation and drives major changes in muscle and liver energy metabolism and rhythmic gene expression. Transcriptional and phosphoproteomic analyses revealed alterations in lipid metabolism and mitochondrial function associated with increased EGFR-JAK-STAT3 signaling. Metabolomic analyses confirmed rhythmic metabolic rewiring with impaired β-oxidation and lipid handling and revealed a pronounced shunt toward sphingolipid and ceramide accumulation. The arthritis-related production of ceramides was most pronounced during the day, which is the time of peak inflammation and increased reliance on fatty acid oxidation. Thus, our data demonstrate that localized joint inflammation drives a time-of-day–dependent build-up of bioactive lipid species driven by rhythmic inflammation and altered EGFR-STAT signaling.
29261896 Brodalumab. 2022 Jan Brodalumab is a monoclonal antibody approved by the United States Food and Drug Administration (FDA) to treat moderate to severe plaque psoriasis in adult patients who have failed treatment with topical and other systemic therapy. In addition to plaque psoriasis, brodalumab has been explored as a potential treatment for other auto-inflammatory diseases, including psoriatic and rheumatoid arthritis. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of brodalumab, pertinent for interprofessional team members for the treatment of patients with indicated inflammatory pathologies.
34287863 Retraction. 2022 Mar Retraction: "Downregulated microRNA-135a ameliorates rheumatoid arthritis by inactivation of the phosphatidylinositol 3-kinase/AKT signaling pathway via phosphatidylinositol 3-kinase regulatory subunit 2," by Yuan Qu, Yu-Ping Zhang, Jing Wu, Li-Gang Jie, Jia-Xin Deng, Dong-Bao Zhao, Qing-Hong Yu, J Cell Physiol. 2019; 17663-17676: The above article, published online on 25 March 2019 in Wiley Online Library (https://onlinelibrary.wiley.com/doi/full/10.1002/jcp.28390), has been retracted by agreement between the journal's Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies between results presented and experimental methods described were found. Thus, the editors consider the conclusions of this article to be invalid.
35432965 Does propolis have any effect on rheumatoid arthritis? A review study. 2022 Apr Rheumatoid arthritis (RA) is a chronic autoimmune disease in which inflammation and oxidative stress play a key role in its pathophysiology. Complementary therapies along with medications may be effective in the control of RA. Propolis is a natural substance extracted from beehives, which have confirmed anti-inflammatory and antioxidant effects. The present study aimed to review the possible effects of propolis on inflammation, oxidative stress, and lipid profile in patients with RA. English articles in online databases such as PubMed‑Medline, AMED, Google Scholar, EMBASE, Scopus, and Web of Science databases were searched. Pieces of evidence show that supplementation with propolis may have therapeutic effects on RA patients. Due to increased inflammation and oxidative stress in the affected joints of RA patients, propolis could inhibit the inflammatory cascades by inhibiting the nuclear factor kappa B pathway and reducing reactive oxygen species, malondialdehyde, and interleukin-17 by increasing some antioxidants. Therefore, inflammation and pain reduce, helping improve and control RA in patients. Further investigations are required with larger sample sizes and different doses of propolis to demonstrate the definite effects of propolis on various aspects of RA.
34782759 A novel cytokine consisting of the p40 and EBI3 subunits suppresses experimental autoimmun 2022 Jan OBJECTIVE: The interleukin (IL)-12 cytokine family is closely related to the development of T helper cells, which are responsible for autoimmune disease enhancement or suppression. IL-12 family members are generally heterodimers and share three α-subunits (p35, p19, and p28) and two β-subunits (p40 and EBI3). However, a β-sheet p40 homodimer has been shown to exist and antagonize IL-12 and IL-23 signaling (1). Therefore, we assumed the existence of a p40-EBI3 heterodimer in nature and sought to investigate its role in immune regulation. METHODS: The presence of the p40-EBI3 heterodimer was confirmed by ELISA, immunoprecipitation, and western blotting. A p40-EBI3 vector and p40-EBI3-Fc protein were synthesized to confirm the immunological role of this protein in mice with collagen-induced arthritis (CIA). The anti-inflammatory effects of p40-EBI3 were analyzed with regard to clinical, histological, and immune cell-regulating features in mice with CIA. RESULTS: Clinical arthritis scores and the expression levels of proinflammatory cytokines (e.g., IL-17, IL-1β, IL-6, and TNF-α) were significantly attenuated in p40-EBI3-overexpressing and p40-EBI3-Fc-treated mice with CIA compared to vehicle-treated mice with CIA. Structural joint damage and vessel formation-related gene expression were also reduced by p40-EBI3 heterodimer treatment. In vitro, the p40-EBI3-Fc protein significantly suppressed the differentiation of Th17 cells and reciprocally induced CD4(+)CD25(+)Foxp3(+) (regulatory T) cells. p40-EBI3 also inhibited osteoclast formation in a concentration-dependent manner. CONCLUSION: In this study, p40-EBI3 ameliorated proinflammatory conditions both in vivo and in vitro. We propose that p40-EBI3 is a novel anti-inflammatory cytokine involved in suppressing the immune response through the expansion of Treg cells and suppression of Th17 cells and osteoclastogenesis.
35364780 Implications of Evolving Disease Classification for Drug Approval in Juvenile Idiopathic A 2022 May The classification of inflammatory arthritis incorporates a sharp divide between diseases of childhood onset, grouped together as juvenile idiopathic arthritis, and diseases such as rheumatoid arthritis that begin by definition in adulthood. An important consequence of this divide is that regulatory authorities and many rheumatologists regard pediatric and adult arthritides as truly different, with the implication that drugs should be evaluated separately for each category. However, it is now clear that most forms of arthritis transcend the pediatric/adult boundary and that agents generally exhibit comparable success irrespective of age of onset, offering new opportunities in drug development and regulation focused on pharmacology and safety rather than efficacy. This paradigm shift will enable advances in arthritis treatment, originating either with adults or children, to translate more rapidly across the age spectrum.
35351939 Blood KL-6 predicts prognosis in primary Sjögren's syndrome-associated interstitial lung 2022 Mar 29 Interstitial lung disease associated with primary Sjögren's syndrome (SJS-ILD) has a variable clinical course. We aimed to investigate the role of blood biomarkers in predicting prognosis for SJS-ILD. Clinical data of 46 SJS-ILD patients were retrospectively reviewed. Plasma biomarker levels, including Krebs von den Lungen-6 (KL-6), CC chemokine ligand 18 (CCL18), chitinase-3-like-1 (YKL-40), interleukin-4 receptor alpha (IL-4Ra), and matrix metalloproteinase-7 (MMP-7) were measured using the multiplex Luminex assays (R&D Systems, Minneapolis, USA). The median follow-up period was 69.0 months. The mean age of the patients was 59.4 years; 17.4% were men. The KL-6 level was significantly higher in non-survivors (n = 12; 119.6 vs. 59.5 pg/mL, P = 0.037) than survivors (n = 34), while the levels of the other biomarkers did not differ. Receiver operating characteristic analysis indicated that KL-6 shows the best performance for predicting survival (area under the curve = 0.705, P = 0.037; best cut-off value = 53.5 pg/mL). Multivariable Cox analysis that was adjusted by age and diffusing capacity for carbon monoxide suggested a high KL-6 level (> 53.5 pg/mL) as an independent prognostic factor for survival (hazard ratio = 5.939, 95% confidence interval 1.312-26.881, P = 0.021). Our results suggest that blood KL-6 might be a useful in predicting the prognosis for patients with SJS-ILD.
35113815 Lysosomal exocytosis of HSP70 stimulates monocytic BMP6 expression in Sjögren's syndrome. 2022 Mar 15 BMP6 is a central cytokine in the induction of Sjögren's syndrome-associated (SS-associated) secretory hypofunction. However, the upstream initiation leading to the production of this cytokine in SS is unknown. In this study, RNA ISH on salivary gland sections taken from patients with SS indicated monocytic lineage cells as a cellular source of BMP6. RNA-Seq data on human salivary glands suggested that TLR4 signaling was an upstream regulator of BMP6, which was confirmed by in vitro cell assays and single-cell transcriptomics of human PBMCs. Further investigation showed that HSP70 was an endogenous natural TLR4 ligand that stimulated BMP6 expression in SS. Release of HSP70 from epithelial cells could be triggered by overexpression of lysosome-associated membrane protein 3 (LAMP3), a protein also associated with SS in several transcriptome studies. In vitro studies supported the idea that HSP70 was released as a result of lysosomal exocytosis initiated by LAMP3 expression, and reverse transcription PCR on RNA from minor salivary glands of patients with SS confirmed a positive correlation between BMP6 and LAMP3 expression. BMP6 expression could be experimentally induced in mice by overexpression of LAMP3, which developed an SS-like phenotype. The newly identified LAMP3/HSP70/BMP6 axis provided an etiological model for SS gland dysfunction and autoimmunity.
35131750 Safety, patient acceptance and diagnostic accuracy of ultrasound core needle biopsy of par 2022 Feb BACKGROUND: Enlargement of the major salivary glands (SGs) is a major risk factor for B-cell lymphoma among patients with primary Sjögren's syndrome (pSS). Ultrasound-guided core needle biopsy (US-guided CNB) could be a novel technique to manage SG enlargement among patients with pSS. OBJECTIVE: Accordingly, this study's main aim was to evaluate the safety, patient tolerance and diagnostic accuracy of US-guided CNB procedure for patients with pSS with major SG enlargement. METHODS: Patients with clinical diagnosis of pSS and a clinical indication for SG biopsy consecutively underwent US-guided CNB between September 2019 and June 2021. These patients were evaluated clinically 1, 2 and 12 weeks after US-guided CNB. Patients were asked to complete a questionnaire about postprocedural complications as well as periprocedural pain, using the Visual Analogue Scale. Complications were categorised as transient (<12 weeks) or persistent (≥12 weeks). RESULTS: US-guided CNB was performed on 30 major salivary glands (22 parotid glands and 8 submandibular glands). The procedure was well tolerated. Transient complications-such as haematoma, swelling-were observed among 43% of patients, and mean periprocedural pain was low. However, no persistent complications were reported during the study's follow-up period. CONCLUSION: US-guided CNB represents a novel approach for the management of patients with pSS with SG enlargement. The procedure showed remarkable patient safety and tolerance, allowing adequate glandular sampling and a definite diagnosis for almost all participating patients without long-term complications.
34861168 Safety and efficacy of subcutaneous ianalumab (VAY736) in patients with primary Sjögren's 2022 Jan 8 BACKGROUND: Sjögren's syndrome is an autoimmune disease characterised by dry eyes and mouth, systemic features, and reduced quality of life. There are no disease-modifying treatments. A new biologic, ianalumab (VAY736), with two modes of suppressing B cells, has previously shown preliminary efficacy. This dose-finding trial aimed to assess the safety and efficacy of different subcutaneous doses of ianalumab in patients with moderate to severe primary Sjögren's syndrome. METHODS: VAY736A2201 was a randomised, parallel, double-blind, placebo-controlled, phase 2b dose-finding study done in 56 centres in 19 countries. Patients aged 18-75 years with primary Sjögren's syndrome with moderate to severe disease activity (European Alliance of Associations for Rheumatology [EULAR] Sjögren's Syndrome Disease Activity Index [ESSDAI] score ≥6) and symptom severity (EULAR Sjögren's Syndrome Patient Reported Index score ≥5) were eligible. Participants were randomly assigned (1:1:1:1) to receive subcutaneous placebo or ianalumab (5 mg, 50 mg, or 300 mg) every 4 weeks for 24 weeks using a secure, online randomisation system. Randomisation was stratified by the ESSDAI score at baseline (≥10 or <10). Study personnel and patients were masked to treatment assignment. The primary outcome was the change in ESSDAI score from baseline to 24 weeks in all randomly assigned patients. Dose-related change in disease activity (ESSDAI) from baseline at week 24 was assessed by multiple comparison procedure with modelling analysis. Safety was measured in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT02962895. FINDINGS: Between June 27, 2017, and Dec 06, 2018, 293 patients were screened, 190 of whom were randomly assigned (placebo n=49, ianalumab 5 mg n=47, ianalumab 50 mg n=47, ianalumab 300 mg n=47). Statistically significant dose-responses were seen for overall disease activity (ESSDAI score) in four of the five dose-response models tested (p<0·025 in four models, p=0·060 in one model). The ESSDAI score decreased from baseline in all ianalumab groups, with the maximal ESSDAI score change from baseline observed in the ianalumab 300 mg group: placebo-adjusted least-squares mean change from baseline -1·92 points (95% CI -4·15 to 0·32; p=0·092). There were four serious adverse events in three patients considered treatment-related (pneumonia [n=1] and gastroenteritis [n=1] in the placebo group; appendicitis plus tubo-ovarian abscess in the same patient in the ianalumab 50 mg group). INTERPRETATION: The study met its primary objective, showing a dose-related decrease in disease activity as measured by ESSDAI at week 24. Overall, ianalumab was well tolerated and safe, with no increase in infections. To our knowledge, this is the first large, randomised, controlled trial in primary Sjögren's syndrome that met its primary endpoint, and its results mean there is potential for more studies of this mechanism in the future. FUNDING: Novartis.
35572537 Interaction Between Non-Coding RNAs and Interferons: With an Especial Focus on Type I Inte 2022 Interferons (IFNs) are a group of cellular proteins with critical roles in the regulation of immune responses in the course of microbial infections. Moreover, expressions of IFNs are dysregulated in autoimmune disorders. IFNs are also a part of immune responses in malignant conditions. The expression of these proteins and activities of related signaling can be influenced by a number of non-coding RNAs. IFN regulatory factors (IRFs) are the most investigated molecules in the field of effects of non-coding RNAs on IFN signaling. These interactions have been best assessed in the context of cancer, revealing the importance of immune function in the pathoetiology of cancer. In addition, IFN-related non-coding RNAs may contribute to the pathogenesis of neuropsychiatric conditions, systemic sclerosis, Newcastle disease, Sjögren's syndrome, traumatic brain injury, lupus nephritis, systemic lupus erythematosus, diabetes mellitus, and myocardial ischemia/reperfusion injury. In the current review, we describe the role of microRNAs and long non-coding RNAs in the regulation of IFN signaling.
34802135 Identification of Human T Follicular Cells in Ectopic Lymphoid Structures. 2022 T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are the two T cell subsets able to interact with B cells driving germinal center (GC) reactions. These T-B interactions are important for protective immune responses within secondary lymphoid tissue. However, the pathological emergence of ectopic lymphoid structures (ELS) that characterize several autoimmune diseases also involves Tfh and Tfr cells. ELS, often with ectopic GCs, can be identified through biopsies. Sjögren's syndrome (SS) is an example of an autoimmune disease where minor salivary gland (MSG) biopsies are often performed for diagnosis and where ELS can be found. Here, we describe a protocol to identify and isolate T follicular cells from MSGs by flow cytometry and immunohistochemistry.
35381122 Rheumatology Continuing Professional Development for Primary Care Clinicians: A Systematic 2022 Apr 5 OBJECTIVE: To determine the quality of published rheumatology-focused continuing professional development (CPD) for primary care clinicians (PCCs) for improving the care of patients with rheumatic diseases. METHODS: The authors conducted a systematic review of CPD focused on rheumatology topics for PCCs. A librarian systematically searched PubMed, Embase, Web of Science, ERIC, CINAHL, and PsycINFO. Studies were limited to those conducted in North America after 1993. An extraction form that included the Medical Education Research Study Quality Instrument and the Kirkpatrick levels of learning outcomes was created through an iterative process and applied to the included articles. RESULTS: 725 articles were retrieved, of which nine were included. Results showed that CPD was directed more at non-inflammatory arthritis than inflammatory arthritis. Autoimmune diseases were underrepresented; four studies discussed rheumatoid arthritis, and one study examined rheumatologic topics broadly. Newer research tended to include multi-modal approaches that combined didactic and active learning strategies, showing an evolution towards more active learning. Though online learning is increasingly popular, interventions were predominantly face-to-face with only a single example of e-learning. Studies were predominantly of moderate quality. CONCLUSION: Published studies of rheumatology-focused CPD are moving towards more interactive teaching modalities and are typically conducted in-person though virtual options for rheumatology-focused CPD should be explored to improve access to CPD. Autoimmune disease is an uncommon topic in CPD and represents an area for future expansion. Efficacy was difficult to assess given that most of the studies assessed for learner satisfaction, knowledge acquisition, or behavior change, whereas only one focused on patient outcomes.
35452855 Sjögren syndrome overlapping with ANCA-associated vasculitis: Four additional cases and s 2022 Jun OBJECTIVES: Sjögren's syndrome (SS) and ANCA-associated vasculitis (AAV) have distinct clinical presentation and evolution, with paucity of reports on overlap syndrome. We aimed to better characterize this entity. METHODS: We report four additional cases from the Montpellier university hospital. We also performed a systematic literature review, according to PRISMA guidelines, in Medline, Embase, Web of science, Cochrane Library, and grey literature. Demographic, clinical, and paraclinical data on SS and AAV were analysed. RESULTS: A total of 3133 articles was identified in databases, with 2695 articles screened for eligibility. After exclusion, we had 30 articles on 40 patients to analyse, in addition to 4 patients from our local recruitment (44 patients overall). Patients were female in 81.8%, with median age at AAV onset of 63.5 years. All patients but one presented with SS before, or concomitantly to the diagnosis of AAV, with a median delay of 12 months between both diagnoses. AAV predominantly had renal involvement (35/44 patients, 79.5%), anti-MPO antibodies being the most frequent (35 patients), even in patients presenting with granulomatosis with polyangiitis. We observed significantly more Raynaud phenomenon and associated auto-immune diseases in the group of non-granulomatous AAV (10 patients versus 1, p = 0.015 and 8 patients versus 0, p = 0.013, respectively). CONCLUSIONS: This is the largest descriptive study on the association between SS and AAV, providing information on this challenging diagnosis and interplay between these two diseases. Particular attention should be paid in the first months after diagnosis, given the specific complications and outcomes of each disease.