Platelet TLR7 is essential for the formation of platelet–neutrophil complexes and low-density neutrophils in lupus nephritis

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a novel autoinflammatory syndrome due to a ubiquitin like modifier activating enzyme 1 (UBA1) somatic mutation, recently discovered in 2020. 1 This mutation affects the major E1 enzyme that initiates ubiquitin conjugation of cellular proteins meant for degradation by proteasomes, where decreased ubiquitination causes accumulation of prominent intracellular vacuoles seen in myeloid and erythroid precursors in the bone marrow. 2 This autoinflammatory disease has a significant hematologic malignancy and thrombotic burden, with an increased incidence of venous thromboembolism (VTE)(36.4%), where deep vein thrombosis (DVT) is more common than pulmonary embolism (PE), with a lower incidence of arterial thrombosis (1.6%). 3 However, limited information is available on the potential mechanisms of thrombosis in patients …

npj Vaccines

Check for updates January 2024 marks the fourth anniver-sary of the identification of SARS-CoV-2 as the causative agent of the COVID-19 epidemic. Since that time, vaccine development has proceeded at an unprecedented and extraordinary pace due to the combined efforts of researchers from academia, industry, government and non-governmental organisations. These efforts, together with regulators, enabled the first vaccines to receive Emergency Use Authorisation (or equivalent) in under 12 months. As of February 2024, 64 vaccines are approved by one or more national regulatory authorities 1. Vaccine platforms include inactivated viruses, mRNA, DNA, recombinant proteins, non-replicating and replicating viral vectors. Immunogens include the spike protein, receptor-binding domain, and spike protein ectodomain. Whilst the estimates of annual global deaths linked to COVID-19 have reduced by as much as …

Nature Communications

Periodontitis, which is induced by repeated bacterial invasion and the ensuing immune reactions that follow, is the leading cause of tooth loss. Periodontal tissue is comprised of four different components, each with potential role in pathogenesis, however, most studies on immune responses focus on gingival tissue. Here, we present a modified ligature-induced periodontitis model in male mice to analyze the pathogenesis, which captures the complexity of periodontal tissue. We find that the inflammatory response in the peri-root tissues and the expression of IL-6 and RANKL by Thy-1.2− fibroblasts/stromal cells are prominent throughout the bone destruction phase, and present already at an early stage. The initiation phase is characterized by high levels of ST2 (encoded by Il1rl1) expression in the peri-root tissue, suggesting that the IL-33/ST2 axis is involved in the pathogenesis. Both Il1rl1- and Il33-deficient mice …

Lupus Science & Medicine

ObjectivePatients with systemic lupus erythematosus (SLE) have increased risk of premature atherosclerosis but the exact mechanisms remains unclear. Flow-mediated dilatation (FMD) is an established non-invasive assessment of vascular endothelial function. Lipoprotein subfractions may be better predictors of FMD than conventional cholesterol measurements. We tested the hypothesis that lipoprotein subfractions are independently associated with FMD.MethodsForty-one consecutive adult patients with SLE without known cardiovascular risk factors or disease were recruited in this cross-sectional study. Endothelial function and early atherosclerosis were assessed by brachial FMD and common carotid artery (CCA) intima-media thickness (IMT). High-density lipoprotein (HDL)/low-density lipoprotein (LDL) subfractions were measured. Machine learning models were also constructed to predict FMD and CCA IMT …

STAR protocols

Cross-linking mass spectrometry (XL-MS) provides low-resolution structural information to model protein structures. Here, we present a protocol to identify cross-links of purified antibody binding to purified human leukocyte antigen (HLA). We describe steps for using a discovery-based XL-MS approach followed by a targeted XL-MS approach. We then detail procedures for using the identified cross-links with other structural data for molecular docking of the antibody to HLA. This protocol has applications for modeling the interacting structure of purified antibody to antigen.For complete details on the use and execution of this protocol, please refer to Ser et al.1

An apparatus for collecting a saliva sample is described herein. In a described embodiment, the apparatus comprises a filter; and a pressure generator operable to generate pressure to cause the saliva sample to be transferred through the filter, the filter being configured to reduce a viscosity of the saliva sample as the saliva sample is transferred through the filter. A method collecting a saliva sample from a user is also described, among other aspects.

The Journal of Clinical Investigation

Nicotinamide adenine dinucleotide (NAD) is essential for embryonic development. To date, biallelic loss-of-function variants in 3 genes encoding nonredundant enzymes of the NAD de novo synthesis pathway — KYNU, HAAO, and NADSYN1 — have been identified in humans with congenital malformations defined as congenital NAD deficiency disorder (CNDD). Here, we identified 13 further individuals with biallelic NADSYN1 variants predicted to be damaging, and phenotypes ranging from multiple severe malformations to the complete absence of malformation. Enzymatic assessment of variant deleteriousness in vitro revealed protein domain–specific perturbation, complemented by protein structure modeling in silico. We reproduced NADSYN1-dependent CNDD in mice and assessed various maternal NAD precursor supplementation strategies to prevent adverse pregnancy outcomes. While for Nadsyn1 …

Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by inflammation in multiple organs. A few treatments for SLE currently exist, including antimalarials, glucocorticoids, immunosuppressants, and two recently approved antibody agents; however, an unmet medical need remains for SLE. In addition, developing new drugs targeting SLE is a challenge since no specific biomarkers exist for the prediction of disease progression or drug response. A new drug candidate, E6742, is a specific antagonist of the toll-like receptors 7/8. To address the challenges for drug development in SLE, the process of developing E6742 utilizes a unique system of the Japan Agency for Medical Research and Development (AMED), the Cyclic Innovation for Clinical Empowerment (CiCLE) program. In the CiCLE program, a Phase 1 study in healthy adults was completed (NCT04683185) and a Phase 1/2 study in …

Introduction Periodontitis as a comorbidity in systemic lupus erythematosus (SLE) is still not well recognized in the dental and rheumatology communities. A meta-analysis and network meta-analysis were thus performed to compare the (i) prevalence of periodontitis in SLE patients compared to those with rheumatoid arthritis (RA) and (ii) odds of developing periodontitis in controls, RA, and SLE. Methods Pooled prevalence of and odds ratio (OR) for periodontitis were compared using meta-analysis and network meta-analysis (NMA). Results Forty-three observational studies involving 7,800 SLE patients, 49,388 RA patients, and 766,323 controls were included in this meta-analysis. The pooled prevalence of periodontitis in SLE patients (67.0%, 95% confidence interval [CI] 57.0-77.0%) was comparable to that of RA (65%, 95% CI 55.0-75.0%) (p>0.05). Compared to controls, patients with SLE (OR=2.64, 95% CI 1.24-5.62, p<0.01) and RA (OR=1.81, 95% CI 1.25-2.64, p<0.01) were more likely to have periodontitis. Indirect comparisons through the NMA demonstrated that the odds of having periodontitis in SLE was 1.49 times higher compared to RA (OR=1.49, 95% CI 1.09-2.05, p<0.05). Discussion Given that RA is the autoimmune disease classically associated with periodontal disease, the higher odds of having periodontitis in SLE are striking. These results highlight the importance of addressing the dental health needs of patients with SLE. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/ identifier CRD42021272876.

The Journal of Infectious Diseases

Background Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). Methods This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. Results aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was …

Community Series-Extremophiles: Microbial Genomics and Taxogenomics, Volume II

Objective: The present systematic review aimed to provide an overview of training load (TL), along with their responses, monitoring during training sessions in highly trained and elite adult women soccer players.Data source: Electronic databases searches (PubMed, Scopus, Web of Science and Ebsco) for relevant studies published in peer-reviewed journals were conducted, and eligibility criteria were based on the PICOS model in accordance with PRISMA guidelines.Study selection: Studies were considered as follows:(a) highly trained and elite adult (> 18 years) women's soccer players;(b) continuous (minimum1-week duration) TL monitoring in the context of the team routine;(c) TL collected from entire training session. Methodological qualitative assessments and risk of bias criteria were used for judging the studies.Data extraction: A total of 1,163 studies were identified, and 16 were included. The selected studies were fully screened to extract the population characteristics; the number of players; a type of study design; region where the study was performed; the main findings.Data synthesis: Accumulated external TL (ETL) during the pre-season was positively correlated to enhanced adaptations in intermittent exercise capacity. Daily ETL was negatively correlated to next-day self-reported fatigue and muscle soreness. Daily internal TL (ITL) was negatively correlated to postsession sleep duration and sleep efficiency. One study showed that higher accumulated player load and total distance were associated with injury.

Nutrients

The cellular and molecular mechanisms of atherosclerosis are still unclear. Type 2 innate lymphocytes (ILC2) exhibit anti-inflammatory properties and protect against atherosclerosis. This study aimed to elucidate the pathogenesis of atherosclerosis development using atherosclerosis model mice (ApoE KO mice) and mice deficient in IL-33 receptor ST2 (ApoEST2 DKO mice). Sixteen-week-old male ApoE KO and ApoEST2 DKO mice were subjected to an 8-week regimen of a high-fat, high-sucrose diet. Atherosclerotic foci were assessed histologically at the aortic valve ring. Chronic inflammation was assessed using flow cytometry and real-time polymerase chain reaction. In addition, saturated fatty acids (palmitic acid) and IL-33 were administered to human aortic endothelial cells (HAECs) to assess fatty acid metabolism. ApoEST2 DKO mice with attenuated ILC2 had significantly worse atherosclerosis than ApoE KO mice. The levels of saturated fatty acids, including palmitic acid, were significantly elevated in the arteries and serum of ApoEST2 DKO mice. Furthermore, on treating HAECs with saturated fatty acids with or without IL-33, the Oil Red O staining area significantly decreased in the IL-33-treated group compared to that in the non-treated group. IL-33 potentially prevented the accumulation of saturated fatty acids within atherosclerotic foci.

medRxiv

Objectives To evaluate the safety, tolerability, pharmacokinetics (PK), biomarker response, and efficacy of E6742 in a phase 1/2 study in patients with systemic lupus erythematosus (SLE). Methods Two sequential cohorts of SLE patients were enrolled and randomized to 12 weeks of twice-daily treatment with E6742 (100 or 200 mg; n = 8 or 9) or placebo (n = 9). Results The proportion of patients with any treatment-emergent adverse events (TEAEs) was 58.8% in the E6742 group (37.5% for 100 mg; 77.8% for 200 mg) and 66.7% in the placebo group. No Common Terminology Criteria for Adverse Events ≥ Grade 3 TEAEs occurred. PK parameter levels were similar between SLE patients and healthy adults in previous phase 1 studies. The interferon gene signature (IGS) and levels of proinflammatory cytokines (interleukin-1β, interleukin-6, tumor necrosis factor-α) after ex-vivo challenge with a Toll-like receptor 7/8 agonist were immediately decreased by E6742 treatment. Dose-dependent improvements in the British Isles Lupus Assessment Group-based Composite Lupus Assessment response were observed at Week 12 in the E6742 (37.5% for 100 mg; 57.1% for 200 mg) and placebo (33.3%) groups. E6742 also had therapeutic effects on other symptoms, including skin inflammation, arthritis, and levels of anti-double-stranded DNA antibodies and complements. Conclusions E6742 had a favorable safety profile and was well tolerated, with marked IGS responses and sufficient efficacy signals in patients with SLE. These results provide the first clinical evidence to support E6742 in the treatment of SLE, and support larger, longer-term clinical trials.

npj Vaccines

The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses. The mRNA-LNP vaccines have desirable physicochemical characteristics, such as small size (~78 nm), low polydispersity index (<0.13), and high encapsulation efficiency (>90 …

International Immunology

Transforming growth factor-β-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including Toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to lysine 63-linked polyubiquitin chain through TAK1-binding proteins (TAB) 2 and TAB3. However, the physiological importance of TAB2 and TAB3 in macrophages is still controversial. A previous study has shown that mouse bone marrow-derived macrophages (BMDMs) isolated from mice double deficient for TAB2 and TAB3 produced tumor necrosis factor (TNF)-α and interleukin (IL)-6 to the similar levels as control wild-type BMDMs in response to TLR ligands such as lipopolysaccharide (LPS) or Pam3CSK4, indicating that TAB2 and …

Rheumatology

Objective To study whether multimodal brain MRI comprising permeability and perfusion measures coupled with machine learning can predict neurocognitive function in young patients with SLE without neuropsychiatric manifestations. Methods SLE patients and healthy controls (HCs) (≤40 years of age) underwent multimodal structural brain MRI that comprised voxel-based morphometry (VBM), magnetization transfer ratio (MTR) and dynamic contrast-enhanced (DCE) MRI in this cross-sectional study. Neurocognitive function assessed by Automated Neuropsychological Assessment Metrics was reported as the total throughput score (TTS). Olfactory function was assessed. A machine learning–based model (i.e. glmnet) was constructed to predict TTS. Results Thirty SLE patients and 10 HCs were studied. Both groups had comparable VBM, MTR, olfactory …

Rheumatology

Objectives To determine characteristics associated with patient-reported treatment success in psoriatic arthritis (PsA). Methods Rheumatologist-diagnosed PsA patients fulfilling the CASPAR classification were recruited from a single center. PsA outcome measures included: 66/68 swollen/tender joint counts, Leeds/SPARCC dactylitis/enthesitis indices, psoriasis body surface area (BSA), and patient-reported outcomes (PROs) including PROMIS. The primary outcome was a patient-reported item: “Today, considering the level of control of your psoriatic arthritis and psoriasis, do you consider your treatment has been successful?” Descriptive and multivariate logistic regression analyses identified clinical predictors of patient-reported treatment success. Patient-reported reasons for lack of treatment success were explored. Results A total of 178 participants had a …

Rheumatology

Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression …

Rheumatology

Objectives Biologic DMARDs (bDMARDs) are widely used in patients with RA, but response to bDMARDs is heterogeneous. The objective of this work was to identify pretreatment proteomic biomarkers associated with RA clinical outcome measures in patients starting bDMARDs. Methods Sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) was used to generate spectral maps of sera from patients with RA before and after 3 months of treatment with the bDMARD etanercept. Protein levels were regressed against RA clinical outcome measures, i.e. 28-joint DAS (DAS28) and its subcomponents and DAS28 <2.6 (i.e. remission). The proteins with the strongest evidence for association were analysed in an independent, replication dataset. Finally, subnetwork analysis was carried out using the Disease Module Detection algorithm …

Rheumatology

Objectives IgA vasculitis (IgAV) in adults has been relatively under-investigated. Since outcomes are worse in other forms of vasculitis with increasing age, we investigated the outcomes of IgAV comparing younger adults (18–34), middle-aged adults (35–64) and elderly patients (≥64 years) focusing on kidney outcomes. Methods We identified patients with renal biopsy-confirmed IgAV nephritis and collected data regarding clinical features and progression to end stage kidney disease (ESKD). The relationship between patient factors and ESKD was analysed by regression. Results We identified 202 cases, 34% aged 18–34, 43% aged 35–64 and 23% elderly (>64 years). Median follow-up was 44 months. Elderly patients were more likely to present with ESKD (23.9%) compared with middle-aged (13.7%) and younger adults (2.9%) (χ2 11.6, P = 0.002 …

Rheumatology

DEAR EDITOR, PMR is a symmetrical, glucocorticoid-sensitive, inflammatory disorder of extracapsular structures [1]. PMR affects chronically mechanically stressed fibrocartilage-containing structures such as sternoclavicular joints, pubic symphysis, entheses and interspinous ligaments. IL-1 generated by activation of the NLRP3 inflammasome, from autoinflammatory stimuli such as calcium pyrophosphate crystals that are commonly found in fibrocartilage, might then be amplified locally by IL-6 and spread contralaterally [2]. Compared with glucocorticoids, the disadvantages of IL-6 inhibition as a therapeutic strategy for PMR include slow onset of benefit and long half-life for washout in the case of adverse effects. An alternative strategy for PMR relapse prevention might be to inhibit IL-1.The potential efficacy of pharmacologically targeting a protein can be investigated by leveraging naturally occurring genetic …

Rheumatology

Objective Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive. Methods Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare. Results Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 …

Rheumatology

Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression …

Rheumatology

Objectives To examine the relationship between adherence to dietary guidelines and the risk of developing RA. Methods Participants in the Malmö Diet and Cancer Study (MDCS) cohort diagnosed with RA were identified through register linkage and validated in a structured review. Four controls per case were selected, matched for sex, year of birth, and year of inclusion in the MDCS. Diet was assessed at baseline (1991–1996) using a validated diet history method. A Diet Quality Index (DQI) based on adherence to the Swedish dietary guidelines including intakes of fibre, vegetables and fruits, fish and shellfish, saturated fat, polyunsaturated fat, and sucrose, was used. The associations between the DQI and its components and the risk of RA were assessed using conditional logistic regression analysis, adjusting for total energy intake, smoking, leisure time physical activity and …

Rheumatology

Objective Interstitial lung disease (ILD) is the leading cause of mortality in SSc. Novel biomarkers are crucial to improve outcomes in SSc-ILD. We aimed to compare the performance of potential serum biomarkers of SSc-ILD that reflect different pathogenic processes: KL-6 and SP-D (epithelial injury), CCL18 (type 2 immune response), YKL-40 (endothelial injury and matrix remodelling) and MMP-7 (ECM remodelling). Methods Baseline and follow-up serum samples from 225 SSc patients were analysed by ELISA. Progressive ILD was defined according to the 2022-ATS/ERS/JRS/ALAT guidelines. Linear mixed models and random forest models were used for statistical analyses. Results Serum levels of KL-6 [MD 35.67 (95% CI 22.44–48.89, P < 0.01)], SP-D [81.13 (28.46–133.79, P < 0.01)], CCL18 [17.07 (6.36–27.77, P < 0.01)], YKL-40 [22.81 (7.19 …

Rheumatology

Objective To investigate pathogenic mechanisms underlying JDM, we defined the effect of type I IFN, IFN-α and IFN-β, on pediatric skeletal muscle function and expression of myositis-related proteins using an in vitro engineered human skeletal muscle model (myobundle). Methods Primary myoblasts were isolated from three healthy pediatric donors and used to create myobundles that mimic functioning skeletal muscle in structural architecture and physiologic function. Myobundles were exposed to 0, 5, 10 or 20 ng/ml IFN-α or IFN-β for 7 days and then functionally tested under electrical stimulation and analyzed immunohistochemically for structural and myositis-related proteins. Additionally, IFN-β-exposed myobundles were treated with Janus kinase inhibitors (JAKis) tofacitinib and baricitinib. These myobundles were also analyzed for contractile force and …

Rheumatology

Objectives Disease flares in the post–coronavirus disease 2019 (COVID-19) vaccination period represent a prominent concern, though risk factors are poorly understood. We studied these flares among patients with idiopathic inflammatory myopathies (IIMs) and other autoimmune rheumatic diseases (AIRDs). Methods The COVAD-1 and -2 global surveys were circulated in early 2021 and 2022, respectively, and we captured demographics, comorbidities, AIRDs details, COVID-19 infection history and vaccination details. Flares of IIMs were defined as (a) patient self-reported, (b) immunosuppression (IS) denoted, (c) clinical sign directed and (d) with >7.9-point minimal clinically significant improvement difference worsening of Patient-Reported Outcomes Measurement Information System (PROMIS) PROMISPF10a score. Risk factors of flares were analysed using regression …

Rheumatology

Objectives To (i) identify threshold values of presenteeism measurement instruments that reflect unacceptable work state in employed r-axSpA patients; (ii) determine whether those thresholds accurately predict future adverse work outcomes (AWO) (sick leave or short/long-term disability); (iii) evaluate the performance of traditional health-outcomes for r-axSpA; and (iv) explore whether thresholds are stable across contextual factors. Methods Data from the multinational AS-PROSE study was used. Thresholds to determine whether patients consider themselves in an ‘unacceptable work state’ were calculated at baseline for four instruments assessing presenteeism and two health outcomes specific for r-axSpA. Different approaches derived from the receiver operating characteristic methodology were used. Validity of the optimal thresholds was tested across contextual factors and …

Rheumatology

Objectives The aim of this study is to investigate the effect of anti-interleukin (IL)-1/-6 biologics on systemic juvenile idiopathic arthritis (sJIA)-associated macrophage activation syndrome (MAS). Methods Demographic, clinical and laboratory data of patients followed up with a diagnosis of sJIA-associated MAS assessed from sixteen paediatric rheumatology centres across the country. The clinical and laboratory features of MAS developing while on biological drugs were compared with those without this treatment. Results One hundred and sixty-two patients were included in the study. Forty-five of the MAS events were detected under the effect of anti-IL-1/-6 biologics, while the patients experiencing the remaining 155 events have not received biological treatment in the last three months. Platelet count [128 (72–232) vs 199 (130–371) 109/l], ferritin level on …

Rheumatology

Objectives The objective of this study was to explore the prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIMs) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after two vaccine doses. We compared BI characteristics and severity among patients with IIMs, patients with other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HCs). Multivariable Cox regression models were used to assess the risk factors for BI, severe BI ,and hospitalizations among patients with IIMs. Results Among the 9449 included …

Rheumatology

Objectives The ASSIST study investigated prescribing in routine psoriatic arthritis (PsA) care and whether the patient reported outcome: PsA Impact of Disease questionnaire (PsAID-12), impacted treatment. This study also assessed a range of patient and clinician factors and their relationship to PsAID-12 scoring and treatment modification. Methods Patients with PsA were selected across the UK and Europe between July 2021-March 2022. Patients completed the PsAID questionnaire, with the results shared with their physician. Patient characteristics, disease activity, current treatment methods, treatment strategies, medication changes and patient satisfaction scores were recorded. Results 503 patients recruited. 36.2% had changes made to treatment, 88.8% of this had treatment escalation. Overall, the mean PsAID-12 score was higher for patients with treatment escalation; the PsAID-12 score was associated with odds of treatment escalation (OR: 1.58; p< 0.0001). However, most clinicians reported PsAID-12 did not impact their decision to escalate treatment, instead supporting treatment reduction decisions. Physician’s assessment of disease activity had the most statistically significant effect on likelihood of treatment escalation, (OR = 2.68, per 1-point score increase). Escalation was more likely in patients not treated with biologic therapies. Additional factors associated with treatment escalation included: patient characteristics, physician characteristics, disease activity and disease impact. Conclusion This study highlights multiple factors impacting treatment decision making for individuals with PsA. PsAID-12 scoring correlates with multiple …

Rheumatology

Objective Attribution of neuropsychiatric symptoms in systemic lupus erythematosus (SLE) relies heavily on clinician assessment. Limited clinic time, variable knowledge, and symptom under-reporting contributes to discordance between clinician assessments and patient symptoms. We obtained attributional data directly from patients and clinicians in order to estimate and compare potential levels of direct attribution to SLE of multiple neuropsychiatric symptoms using different patient-derived measures. Methods Quantitative and qualitative data analysed included: prevalence and frequency of neuropsychiatric symptoms, response to corticosteroids, and concurrence of neuropsychiatric symptoms with non-neuropsychiatric SLE disease activity. SLE patients were also compared with controls and inflammatory arthritis (IA) patients to explore attributability of neuropsychiatric …

Rheumatology

Objectives To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. Methods YP aged 14–24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (one or more inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. Results Forty-seven YP …

Rheumatology

Objectives We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). Methods In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. Results We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone …

Rheumatology

Background Tuberculosis (TB) is a highly prevalent disease associated with significant morbidity and mortality globally, and is reported to be associated with the onset of autoimmunity. This study investigated the association between TB and the incidence of systemic vasculitides (SV). Methods Data were obtained from the South Korean National Claims database to identify patients with TB and controls (who had undergone appendectomy). The overall occurrence of SV and disease subtypes during the observation period was compared between the two groups. Adjusted Cox proportional hazards regression and Kaplan–Meier analysis were performed to identify the relationship between TB and SV and to compare SV incidence. Results We identified 418 677 patients with TB and 160 289 controls. The overall SV incidence rate was 192/1,000 000 person …

Rheumatology

Objectives In bio-naïve patients with PsA initiating a TNF inhibitor (TNFi), we aimed to identify baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission (primary objective) and DAPSA28 moderate response at 6 months, as well as drug retention at 12 months across 13 European registries. Methods Baseline demographic and clinical characteristics were retrieved and the three outcomes investigated per registry and in pooled data, using logistic regression analyses on multiply imputed data. In the pooled cohort, selected predictors that were either consistently positive or negative across all three outcomes were defined as common predictors. Results In the pooled cohort (n = 13 369), 6-month proportions of remission, moderate response and 12-month drug retention were 25%, 34% and 63% in patients with available data (n …