Inhibition of Complex I of the Respiratory Chain, but Not Complex III, Attenuates Degranulation and Cytokine Secretion in Human Skin Mast Cells.

The mechanisms of mast cell (MC) degranulation and MC-driven skin symptoms are well-described. In contrast, data about the role of mitochondrial respiration for immune functions of human skin MCs are lacking. Oxygen consumption rate (OCR) in primary human skin MCs during IgE-mediated activation in the absence of glucose was examined using a metabolic flux analyzer.

Towards the identification of novel autoantibodies in Sjögren's syndrome.

Primary Sjögren's syndrome may be difficult to diagnose when antibodies against Ro/SSA are lacking, and can be grouped in at least four clusters indicating different pathophysiological pathways. Novel biomarkers, in particular autoantibodies, would be helpful in diagnosing Sjögren's syndrome and in further identification and characterisation of the clusters.In this review, we describe new technologies that may be utilised in the rapid identification of novel autoantibodies, and an example of how well characterised patients, here from the HarmonicSS cohort, are a prerequisite in the discovery of clinically meaningful biomarkers.

Challenges in non-radiographic axial spondyloarthritis.

Non-radiographic axial spondyloarthritis (nr-axSpA) is part of the spectrum or continuum of axSpA and is characterized by the absence of definite structural damage in the sacroiliac joints. The introduction of the concept of axSpA with two - non-radiographic and radiographic - stages stimulated activities related to the improvement of early diagnosis and treatment of this disease, but also opened a number of controversial topics in the field. In this article, we are discussing several challenges related to the concept of nr-axSpA, the diagnosis, and the treatment in the historical context and in the light of the recent data.

Obstetric outcomes in women with rheumatic disease and COVID-19 in the context of vaccination status.

Objective: To describe obstetric outcomes based on COVID-19 vaccination status, in women with rheumatic and musculoskeletal diseases (RMDs) who developed COVID-19 during pregnancy.

Methods: Data regarding pregnant women entered into the COVID-19 Global Rheumatology Alliance registry from 24 March 2020-25 February 2022 were analysed. Obstetric outcomes were stratified by number of COVID-19 vaccine doses received prior to COVID-19 infection in pregnancy.

Antigen-specific immune reactions by expanded CD8 T cell clones from HLA-B*27-positive patients with spondyloarthritis.

Spondyloarthritis (SpA) is a chronic inflammatory disease that is tightly linked to HLA-B*27 but the pathophysiological basis of this link is still unknown. It is discussed whether either the instability of HLA-B*27 molecules triggers predominantly innate immune reactions or yet unknown antigenic peptides presented by HLA-B*27 induce adaptive autoimmune reactions by CD8 T cells. To analyze the pathogenesis of SpA, we here investigated the T cell receptor (TCR) usage and whole transcriptomes of CD8 single cells from synovial fluid of HLA-B*27-positive SpA patients and HLA-B*27-negative controls.

Recapture and retreatment rates with ixekizumab after withdrawal of therapy in patients with axial spondyloarthritis: results at week 104 from a randomised placebo-controlled withdrawal study.

Objectives: To evaluate the recapture of response with open-label (OL) ixekizumab (IXE) retreatment at week 104 in patients with axial spondyloarthritis who flared after withdrawal of IXE therapy.

Methods: COAST-Y (NCT03129100) is a phase III extension study that included a double-blind, placebo-controlled, randomised withdrawal-retreatment period (RWRP). Patients who achieved remission (Ankylosing Spondylitis Disease Activity Score (ASDAS) <1.

Development and External Validation of a Model Predicting New-Onset Chronic Uveitis at Different Disease Durations in Juvenile Idiopathic Arthritis.

Objective: To develop and externally validate a prediction model for new-onset chronic uveitis in children with juvenile idiopathic arthritis (JIA) for clinical application.

Methods: Data from the international Pharmachild registry were used to develop a multivariable Cox proportional hazards model. Predictors were selected by backward selection, and missing values were handled by multiple imputation.

Local immune cell contributions to fracture healing in aged individuals - A novel role for interleukin 22.

With increasing age, the risk of bone fractures increases while regenerative capacity decreases. This variation in healing potential appears to be linked to adaptive immunity, but the underlying mechanism is still unknown. This study sheds light on immunoaging/inflammaging, which impacts regenerative processes in aging individuals.

Repolarization indicates electrical instability in ventricular arrhythmia originating from papillary muscle.

Aims: Cardiac arrhythmia originating from the papillary muscle (PM) can trigger ventricular fibrillation (VF) and cause sudden cardiac death even in the absence of structural heart disease. Most premature ventricular contractions, however, are benign and hitherto difficult to distinguish from a potentially fatal arrhythmia. Altered repolarization characteristics are associated with electrical instability, but electrophysiological changes which precede degeneration into VF are still not fully understood.

Deep Learning Detects Changes Indicative of Axial Spondyloarthritis at MRI of Sacroiliac Joints.

Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection.

Age-related increase of mitochondrial content in human memory CD4+ T cells contributes to ROS-mediated increased expression of proinflammatory cytokines.

Cellular metabolism modulates effector functions in human CD4 T (Th) cells by providing energy and building blocks. Conversely, cellular metabolic responses are modulated by various influences, e.g.

Keep an Eye on the Back: Spondyloarthritis in Patients With Acute Anterior Uveitis.

Objectives: This study was undertaken to analyze the prevalence of spondyloarthritis (SpA) in patients with acute anterior uveitis (AAU), to identify parameters associated with the presence of SpA, and to evaluate the performance of referral algorithms for identifying patients with a high probability of having SpA.

Methods: Prospectively recruited consecutive patients with noninfectious AAU underwent structured rheumatologic assessment including magnetic resonance imaging of the sacroiliac joints, allowing a definitive diagnosis/exclusion of concomitant SpA. Fisher's exact test and Mann-Whitney U test were used to compare AAU patients with SpA and AAU patients without SpA.

Efficacy, Immunogenicity and Safety of Vaccination in Pediatric Patients With Autoimmune Inflammatory Rheumatic Diseases (pedAIIRD): A Systematic Literature Review for the 2021 Update of the EULAR/PRES Recommendations.

Background: In 2011, the first European League Against Rheumatism (EULAR) vaccination recommendations for pediatric patients with autoimmune inflammatory rheumatic diseases (pedAIIRD) were published. The past decade numerous new studies were performed to assess the safety, efficacy and immunogenicity of vaccinations in pedAIIRD. A systematic literature review (SLR) was therefore performed to serve as the basis for the updated 2021 EULAR/PRES recommendations.

EULAR/PRES recommendations for vaccination of paediatric patients with autoimmune inflammatory rheumatic diseases: update 2021.

Objectives: Recent insights supporting the safety of live-attenuated vaccines and novel studies on the immunogenicity of vaccinations in the era of biological disease-modifying antirheumatic drugs in paediatric patients with autoimmune/inflammatory rheumatic diseases (pedAIIRD) necessitated updating the EULAR recommendations.

Methods: Recommendations were developed using the EULAR standard operating procedures. Two international expert committees were formed to update the vaccination recommendations for both paediatric and adult patients with AIIRD.

Mechanical forces couple bone matrix mineralization with inhibition of angiogenesis to limit adolescent bone growth.

Bone growth requires a specialised, highly angiogenic blood vessel subtype, so-called type H vessels, which pave the way for osteoblasts surrounding these vessels. At the end of adolescence, type H vessels differentiate into quiescent type L endothelium lacking the capacity to promote bone growth. Until now, the signals that switch off type H vessel identity and thus limit adolescent bone growth have remained ill defined.

MRI lesions of the spine in patients with axial spondyloarthritis: an update of lesion definitions and validation by the ASAS MRI working group.

Objectives: Spinal MRI is used to visualise lesions associated with axial spondyloarthritis (axSpA). The ASAS MRI working group (WG) updated and validated the definitions for inflammatory and structural spinal lesions in the context of axSpA.

Methods: After review of the existing literature on all possible types of spinal MRI pathologies in axSpA, the group (12 rheumatologists and two radiologists) consented on the required revisions of lesion definitions compared with the existing nomenclature of 2012.

The impact of psoriasis on the clinical characteristics, disease burden and treatment patterns of peripheral spondyloarthritis.

Objectives: To evaluate the clinical characteristics, disease burden, and treatment patterns of peripheral spondyloarthritis (pSpA) patients with and without psoriasis using data from the ASAS-perSpA study.

Methods: We included 433 patients who had a diagnosis of pSpA according to the rheumatologist's diagnosis from the ASAS-PerSpA study. The presence of a personal history of psoriasis was defined as the presence of signs of psoriasis at physical examination or the presence of psoriatic nail dystrophy, including onycholysis, pitting and hyperkeratosis, or a history of psoriasis diagnosed by a physician.

Follow-Up Comparison of Fluorescence Optical Imaging With Musculoskeletal Ultrasound for Early Detection of Psoriatic Arthritis.

Objectives: Early diagnosis of psoriatic arthritis (PsA) is crucial for a patient outcome but hampered by heterogenous manifestation and a lack of specific biomarkers. We recently showed that fluorescence optical imaging (FOI) can differentiate between patients with confirmed and suspected PsA. This study aims to follow-up (FU) patients with confirmed and suspected PsA focusing on patients with a change from suspected to confirmed PsA by the use of FOI in comparison with musculoskeletal ultrasound (MSUS).

Temporary antimetabolite treatment hold boosts SARS-CoV-2 vaccination-specific humoral and cellular immunity in kidney transplant recipients.

Transplant recipients exhibit an impaired protective immunity after SARS-CoV-2 vaccination, potentially caused by mycophenolate (MPA) immunosuppression. Recent data from patients with autoimmune disorders suggest that temporary MPA hold might greatly improve booster vaccination outcomes. We applied a fourth dose of SARS-CoV-2 vaccine to 29 kidney transplant recipients during a temporary (5 weeks) MPA/azathioprine hold, who had not mounted a humoral immune response to previous vaccinations.

Oral anticoagulants (NOAC and VKA) in chronic thromboembolic pulmonary hypertension.

EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study in patients with pulmonary hypertension treated with riociguat. Patients were followed for 1-4 years, and the primary outcomes were adverse events (AEs) and serious AEs (SAEs), including embolic/thrombotic and hemorrhagic events. Here we report data on patients with chronic thromboembolic pulmonary hypertension (CTEPH) receiving a vitamin K antagonist (VKA; n = 683) or a non-vitamin K antagonist oral anticoagulant (NOAC; n = 198) at baseline.