Lessons from organoid engineering for rheumatic disease.

Organoids are three-dimensional (3D) culture models developed from stem cells that aim to mimic both organ structure and functions. This technique is developing in the field of translational research, emerging as a key model through its multiple applications. Numerous models have been developed from various organs, allowing disease modelling, drug screening and hopes in regenerative medicine.

French recommendations for assessing and managing the risk of cancer before the initiation of targeted therapies for chronic rheumatic inflammatory diseases.

Objective: Chronic inflammatory rheumatic diseases (CIRDs) are associated with a higher risk of cancer due to persistent inflammation, immune dysregulation, and immunomodulatory therapies. The growing use of targeted therapies necessitates systematic cancer risk assessment prior to treatment initiation.

Objective: To develop practical recommendations for cancer risk assessment and management before initiating targeted therapies in patients with CIRDs, while balancing therapeutic benefits with oncologic safety.

Primary Sjögren's Disease: a review of unmet need, outcome measures, therapeutic advances and health economic impacts. Lessons from the NEw Clinical Endpoints in primary Sjögren's Syndrome: an Interventional Trial based on stratifYing patients (NECESSITY) Innovative Health Initiative (IHI).

Primary Sjögren's disease (pSjD) is an autoimmune rheumatic disease involving exocrine glands and associated with high symptom burden (dryness, fatigue, pain), systemic features and salivary gland dysfunction. B-cell hyperactivity is common, with an increased risk of mucosa-associated lymphoid tissue lymphoma. This review describes the unmet need, scientific validity of outcome measures, optimisation of clinical trial design, therapeutic advances and how clinical improvement relates to health-related quality of life, additional quality-adjusted life years and economic benefit in pSjD.

JAK inhibitor withdrawal causes a transient pro-inflammatory cascade: A potential mechanism for major adverse cardiac events.

Objective: Our objective was to define the effect of JAK inhibitor (JAKinib) withdrawal on JAK/STAT biochemical response in the context of systemic rheumatic diseases.

Methods: We tested Type I (bind kinase active conformation) and Type II (bind kinase inactive conformation) JAKinibs in vitro using mesenchymal stromal cells (MSCs) and human umbilical vein endothelial cells (HUVECs). We translated our findings in vivo studying NK cells from rheumatoid arthritis (RA) patients treated with Type I JAKinibs or methotrexate.

Cluster analysis identifies three clinical patterns of patients with systemic autoimmune diseases and anti-Ku antibodies.

Objective: To determine distinct patterns of patients with autoimmune diseases harbouring anti-Ku antibodies and their respective prognosis.

Methods: Anti-Ku-positive patients were retrieved through four immunology departments. Clusters were derived from unsupervised multiple correspondence analysis, not including the disease's diagnosis, followed by hierarchical clustering.

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.

Development of salivary gland organoids derived from patient biopsies: a functional model of Sjögren's disease.

Objectives: Salivary gland epithelial cells (SGECs) play a key role in Sjögren's disease (SjD) as an active contributor to the pathogenesis. Current models lack clear epithelial readouts. Our aim was to establish a more advanced model by developing salivary gland organoids (SGOs) from labial salivary gland biopsies (LSGBs) of SjD patients and sicca controls.

CAR T-cell therapy in autoimmune diseases: where are we and where are we going?

Chimeric antigen receptor (CAR)-based therapies developed for the treatment of haematological malignancies have recently been repurposed to treat refractory systemic autoimmune diseases. In this Review we critically discuss the current data available on the use of CAR-based therapy in systemic autoimmune diseases, the current challenges, and the potential next steps toward their implementation into clinical practice. Beyond the targeting of B cells via CD19, we discuss the advantages and potential pitfalls of targeting plasma cells (B-cell Maturation Antigen or CD138) and other non-immune targets, such as fibroblast activated protein, and of aiming to restore immune homeostasis using CAR T regulatory cells.

Isolated anti-SS-B (La) antibodies: rare occurrence and lack of diagnostic value.

Objective: Anti-SS-B antibodies are often associated with anti-SS-A in Sjögren's disease. Compared to anti-SS-A antibody positivity, the significance of the immunological profile anti-SS-B positive/anti-SS-A negative remains controversial. We aimed to evaluate the prevalence and diagnostic significance of isolated anti-SS-B antibodies.

Impact of Sjögren's disease on quality of sexual life using the Qualisex score.

Objective: This study aimed to assess the impact of Sjögren disease (SjD) on the quality of sexual life and its determinants using the Qualisex questionnaire.

Methods: The Qualisex questionnaire was administered to participants within the ASSESS cohort, a French national multicentric prospective cohort of individuals with SjD. Patients' characteristics and psychometric evaluations were also collected.

Distinct Pathophysiologic Pathways Support Stratification of Sjögren's Disease Based on Symptoms, Clinical, and Routine Biological Data.

Objective: Recently, three distinct phenotypes of patients with Sjögren disease (SjD) have been described based on cluster analysis: B cell active with low symptoms (BALS), high systemic activity (HSA), and low systemic activity with high symptoms (LSAHS). We aimed to assess whether these clusters were associated with distinct biomarkers and the prognostic value of interferon (IFN) signature.

Methods: The Assessment of Systemic Signs and Evolution in Sjögren's Syndrome cohort is a 20-year prospective cohort of patients with SjD.

mA RNA methylation controls salivary gland epithelial cell function and has a protective role in Sjögren's disease.

Objectives: The RNA epitranscriptomic modification known as -methyladenosine (mA) represents a novel mechanism of gene regulation that is poorly understood in human autoimmune diseases. Our research explores the role of this RNA mA modification in salivary gland epithelial cells (SGEC) and its impact on the pathogenesis of Sjögren's disease (SjD).

Methods: SGECs from SjD patients and controls were analysed for mA writers METTL3 and METTL14 expression using RNA-seq, quantitative PCR and immunohistochemistry.

Clinical, biological, prognostic characteristics of patients with immune-mediated thrombotic thrombocytopenic purpura and Sjögren's disease.

Objectives: The association between immune-mediated thrombotic thrombocytopenic purpura (iTTP) and Sjögren disease (SjD) has been poorly investigated. This study presents the first retrospective cohort of iTTP-SjD aiming to identify risk factors for iTTP occurrence in SjD patients and examine their clinical course.

Methods: Patients with iTTP-SjD were identified within the French TTP Registry based on American College of Rheumatology/European League Against Rheumatism 2016 criteria.

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

Fine mapping and bioinformatic analysis of the genetic risk association in Sjögren's Disease (SjD) and Systemic Lupus Erythematosus (SLE) identified five common SNPs with functional evidence in immune cell types: rs4938573, rs57494551, rs4938572, rs4936443, rs7117261. Functional interrogation of nuclear protein binding affinity, enhancer/promoter regulatory activity, and chromatin-chromatin interactions in immune, salivary gland epithelial, and kidney epithelial cells revealed cell type-specific allelic effects for all five SNPs that expanded regulation beyond effects on and expression. Mapping the local chromatin regulatory network revealed several additional genes of interest, including .

Immune Checkpoint Inhibitor-induced Sicca Syndrome.

The development of sicca in patients treated with immune checkpoint inhibitors (ICIs) is undoubtedly an underestimated complication, but one whose functional consequences and impact on quality of life are significant for patients. This update aims to review the frequency of this complication and different clinical pictures. The authors also propose a diagnostic and therapeutic approach to guide clinicians in daily practice.

Identification of distinct subgroups of Sjögren's disease by cluster analysis based on clinical and biological manifestations: data from the cross-sectional Paris-Saclay and the prospective ASSESS cohorts.

Background: Sjögren's disease is a heterogenous autoimmune disease with a wide range of symptoms-including dryness, fatigue, and pain-in addition to systemic manifestations and an increased risk of lymphoma. We aimed to identify distinct subgroups of the disease, using cluster analysis based on subjective symptoms and clinical and biological manifestations, and to compare the prognoses of patients in these subgroups.

Methods: This study included patients with Sjögren's disease from two independent cohorts in France: the cross-sectional Paris-Saclay cohort and the prospective Assessment of Systemic Signs and Evolution of Sjögren's Syndrome (ASSESS) cohort.

Inclusion-body myositis associated with Sjögren's disease: clinical characteristics and comparison with other Sjögren-associated myositis.

Objectives: To describe the characteristics of patients with Sjögren's disease (SjD) and inclusion-body myositis (IBM), and how they compare to SjD patients with other inflammatory myopathies (IM).

Methods: Patients were retrospectively recruited from 13 French centres and included if they met the ACR/EULAR criteria for SjD and for IM. They were categorized as SjD-IBM if sub-criteria for IBM were met, or as SjD-other IM if not.

Characterisation of airway disease associated with Sjögren disease.

Objective: Although airway disease associated with Sjögren's disease (Sjo-AD) is common, it is poorly studied compared with interstitial lung disease (ILD). In this study, we aimed to assess factors associated with Sjo-AD, the characteristics and prognosis of this manifestation.

Methods: We performed a retrospective multicentric study involving nine centres.

Pregnancy outcomes in women with primary Sjögren's syndrome: an analysis of data from the multicentre, prospective, GR2 study.

Background: Adverse pregnancy outcomes in women with primary Sjögren's syndrome have only been evaluated retrospectively using heterogeneous methods and with contradictory results. We aimed to describe adverse pregnancy, delivery, and birth outcome risks in pregnant women with primary Sjögren's syndrome compared with those of a matched general population in France, and to identify factors predictive of disease flares or adverse pregnancy outcomes.

Methods: We conducted a multicentre, prospective, cohort study in France using the GR2 (Groupe de Recherche sur la Grossesse et les Maladies Rares) registry.

[F]FDG-PET/CT in Polymyalgia Rheumatica: An Update and Future Aspects.

Polymyalgia rheumatica (PMR) is an inflammatory disorder usually diagnosed in patients older than 50 years of age. It is characterized by sudden onset pain and prolonged morning stiffness in the scapular and/or pelvic girdle, sometimes debilitating and accompanied by constitutional symptoms such as weight loss. In approximately 20% of the cases, it is linked to giant cell arteritis (GCAV) representing a disease continuum.