A germline IκBα mutation outside the signal reception domain blocks nuclear translocation of NFκB1 and associates with autoinflammation-like features.

Objectives: IκBα controls the canonical activation of NFκB. IκBα gain-of-function due to NFKBIA variants affecting the N-terminus of IκBα-especially residues 32 and 36-manifests with combined immunodeficiency. The role of NFKBIA variants affecting other IκBα domains has not been described.

Kappa free light chain concentration in serum is reduced after CD20-depletion with ocrelizumab.

Background: Kappa free light chains (KFLC), a byproduct of immunoglobulin (Ig) synthesis by B-lineage cells, can serve as an indicator for inflammatory activity. In multiple sclerosis (MS), especially the intrathecal KFLC production has gained increasing importance as a biomarker for central nervous system (CNS) inflammation and was included into the proposed 2024 revision of the McDonald criteria. In contrast, studies investigating the significance of KFLC in serum and the effects of disease-modifying therapies (DMT) on KFLC serum concentration in MS are rare.

No difference in endothelial microvasculation measured by peripheral arterial tonometry in patients with Sjögren's disease and matched controls.

Sjögren's disease (SjD) is a connective tissue autoimmune disorder characterized by inflammatory infiltration of the exocrine glands, leading to symptoms such as dryness, pain, and fatigue. Additionally, up to 50% of patients may experience extraglandular manifestations. SjD patients face a higher cardiovascular risk, including severe events like myocardial infarction and strokes, partly due to an increased likelihood of subclinical atherosclerosis.

Management of disease-modifying therapies in multiple sclerosis and comorbid rheumatoid arthritis.

Background: Comorbid autoimmune disorders, including rheumatoid arthritis (RA), are common in people with multiple sclerosis (MS). Both conditions share pathogenic similarities, enabling potential overlap in treatments. While numerous disease-modifying therapies (DMT) are approved for MS and new options are under clinical trial, their effectiveness in RA varies.

Macular Microvasculature Is Different in Patients with Primary Sjögren's Disease Compared to Healthy Controls.

: This study investigates the macular microvasculature in a large cohort of primary Sjögren's disease (SjD) patients using optical coherence tomography angiography (OCTA), focusing on how disease duration, activity, and hydroxychloroquine (HCQ) treatment influence retinal microcirculation. A total of 106 eyes (53 SjD patients) and 70 eyes (35 age- and gender-matched healthy controls (HCs)) were examined. The vessel area density (VAD, %) and foveal avascular zone (FAZ, mm2) were measured in three retinal layers: Superficial Vascular Plexus (SVP), Intermediate Capillary Plexus (ICP), and Deep Capillary Plexus (DCP), respectively, in three peri-macular circular sectors (c1, c2, c3) each.

Advancing research on regulatory autoantibodies targeting GPCRs: Insights from the 5th international symposium.

The 5th International Symposium on Regulatory Autoantibodies Targeting GPCR (RAB-GPCRs) advanced the understanding of the significant role played by autoantibodies targeting G-protein-coupled receptors (GPCRs) in various human diseases. Once considered passive markers, RAB-GPCRs are now recognized as active modulators of cellular signaling, immune regulation, and inflammation. The symposium highlighted their involvement in multiple prominent pathologies, including autoimmune diseases, cardio- and cerebrovascular diseases, and neuroimmunologic disorders such as myalgic encephalomyelitis/chronic fatigue syndrome and post-COVID-19 syndrome (ME/CFS/PCS), as well as solid organ and hematopoietic stem cell transplantation (SOT/HSCT).

Anti-VGLUT2 autoantibodies in neurological diseases.

Autoantibodies are important biomarkers for the diagnosis of autoimmune diseases that help to determine treatment strategies and to understand disease pathology. Despite the increasing numbers of neuronal autoantibody discoveries, there are still patients presenting with neurological autoimmune diseases and so far uncharacterized autoantibodies. Between 12/2016 and 06/2024, we collected sera of 314 patients with a distinct uncharacterized IgG pattern in neuronal tissue indirect immunofluorescence assay (IIFA).

Variants in the DDX6-CXCR5 autoimmune disease risk locus influence the regulatory network in immune cells and salivary gland.

Objectives: Sjögren's disease (SjD) and systemic lupus erythematosus (SLE) share genetic risk at the DDX6-CXCR5 locus (11q23.3). Identifying and functionally characterising shared SNPs spanning this locus can provide new insights into common genetic mechanisms of autoimmunity.

CXCR4-Targeted Imaging in Takayasu Arteritis Using 68Ga-Pentixafor PET/CT.

We report a case of a 64-year-old woman with Takayasu arteritis who underwent chemokine receptor CXCR4-targeted whole-body 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT) for further evaluation of disease activity and exclusion of concurrent inflammatory diseases. 68Ga-Pentixafor PET demonstrated CXCR4-positive inflammatory cell infiltrates in the aortic wall, and active disease was further confirmed by 18F-fluorodeoxyglucose (FDG) PET/CT. Moreover, 68Ga-Pentixafor identified a CXCR4-positive pelvic bone lesion, and the patient was subsequently diagnosed with diffuse large B-cell lymphoma.

Reappraisal of IgG subclass deficiencies: a retrospective comparative cohort study.

Objective: The aim of the present study was to investigate the clinical spectrum of IgG subclass deficiencies (IgGSDs) and assess the relative clinical significance of diagnosing each specific IgGSD disorder as compared to the common variable immunodeficiency (CVID).

Methods: The clinical spectrum and immunological findings from 96 patients, diagnosed with diverse IgGSDs, were retrospectively evaluated. Specific IgGSDs were compared with each other and a cohort of 270 patients with CVID.

A novel hemizygous nonsense variant in DOCK11 causes systemic inflammation and immunodeficiency.

Hemizygous germline loss-of-function variants in DOCK11, the gene encoding the dedicator of cytokinesis 11 (DOCK11) have been recently identified to cause variable immunodeficiency and immune dysregulation. Features of immune dysregulation have been reported in all so far identified male patients with damaging variants in DOCK11, commonly manifesting with autoimmune cytopenias, inflammatory bowel disease, benign lymphoproliferation and systemic inflammation. In this study, we identified a novel variant in DOCK11 (c.

T cells of patients with systemic sclerosis or Sjögren's disease display an aberrant metabolic state and memory phenotype in blood and lungs.

Objectives: Systemic sclerosis (SSc) and Sjögren's disease (SjD) are characterized by systemic inflammation. Although for both entities lymphocyte involvement is reported, the contribution of T-cell responses to lung manifestation of SSc and SjD remains elusive. Therefore, we aimed for systematically investigating T-cell responses in blood and lungs of patients with SSc or with SjD.

Janus kinase inhibitors show a longer drug survival than biologics in a real-world cohort of patients with rheumatoid arthritis - a retrospective analysis from the RHADAR database.

Numerous biologic and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs) have been approved for treating rheumatoid arthritis (RA), including Janus kinase inhibitors (JAKi), rituximab, abatacept, interleukin-6 inhibitors (IL-6i) and tumor necrosis factor inhibitors (TNFi). Real-world data regarding treatment persistence and drug survival in the time period following the approval of JAKI are limited. To investigate the persistence and drug survival of different (b/tsDMARDs) in patients with RA based on real-world data from German outpatients.

Anti-CD74 autoantibodies in axial spondyloarthritis as biomarkers for activity and severity of disease but not for tumour necrosis factor inhibitor retention: data from the Swiss Clinical Quality Management in rheumatic diseases cohort.

Objectives: Anti-CD74 antibodies (Abs) have been proposed as a diagnostic biomarker in axial spondyloarthritis (axSpA). The aims of this study were to evaluate the association of these Abs with disease activity parameters in axSpA and to assess their predictive value for tumour necrosis factor inhibitor (TNFi) treatment effectiveness.

Methods: Patients diagnosed with axSpA in the Swiss Clinical Quality Management registry with available biosamples and a measurement of IgA anti-CD74 Abs were included in this cohort study.

Identification of novel autoantibodies in Sjögren's disease.

Introduction: The diagnosis of Sjögren's disease (SjD) in patients without autoantibodies against Ro/SSA is a major challenge. We aimed to identify novel autoantibodies in SjD that may facilitate the diagnostic procedure for Ro/SSA negative SjD.

Methods: IgG and IgA autoantibody reactivity of 94 potential candidate autoantigens for SjD, selected from a discovery screen of 1,629 human antigens coupled to Luminex beads and prior knowledge about potential biological relevance, were examined in serum of SjD patients (n=347) using Luminex and ELISA technology.

A comparative cross-sectional study of psychological distress, fatigue, and physical activity in patients with rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's disease.

Introduction: Anxiety and depression are common in patients with rheumatic diseases, but their impact across conditions like rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's disease (SjD) is still not well understood. This study aims to compare depression, anxiety, and fatigue, and their effects on disease activity and physical activity in these conditions.

Methods: From January 2019 to March 2021, patients with RA, primary SjD and SLE were assessed consecutively in a monocentric cross-sectional study at the rheumatology outpatient clinic of the Hannover Medical School.

Disease-modifying strategies: Targeting protein kinases in multiple sclerosis and other autoimmune disorders.

A wide variety of immunomodulatory therapies are already available for the treatment of multiple sclerosis (MS). Through fundamental insights from basic research with a gain of knowledge in the pathological processes underlying MS, the exploration of additional medical compounds within clinical trials has been ignited. Emerging novel medications with innovative mechanisms of action are being introduced.

Impact of time to diagnosis in patients with primary Sjögren's syndrome: a cross-sectional study.

Objectives: Primary Sjögren's syndrome is a chronic autoimmune disease with an inflammation of exocrine glands. It can be difficult to diagnose due to frequently unspecific symptoms, such as fatigue and myalgia. The aim of this study was to investigate the journey of patients prior to the diagnosis of primary Sjögren's syndrome and how this affects the patient-reported outcomes.

Optical coherence tomography angiography to assess for retinal vascular changes in Neuro-Sjögren.

Background: Sjögren's syndrome is an autoimmune disease characterized by sicca symptoms and various extraglandular manifestations including vasculitis. Neurological involvement occurs frequently (Neuro-Sjögren) and often mimics immune neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP).

Objectives: We aim to assess relevant differences in vessel density (VD) in Optical Coherence Tomography Angiography (OCTA) in those diseases to use it as an easily available diagnostic tool.

Does Concomitant Use of Methotrexate with JAK Inhibition Confer Benefit for Cardiovascular Outcomes? A Commentary.

This commentary explores the potential cardiovascular (CV) benefits of combining methotrexate (MTX) and Janus kinase inhibitors (JAKis) in the treatment of rheumatoid arthritis (RA). While European guidelines recommend MTX as first-line treatment, concerns about the CV risks associated with JAKis have emerged. This article reviews the existing literature to assess the role of concomitant MTX in reducing CV risk when used with JAKis.