German Rheumatism Research Centre

Zusammenfassung Regelmäßige Bewegung und Sport sind zentrale Elemente kindlicher Entwicklung – physisch, psychosozial und emotional. Auch Kinder und Jugendliche mit rheumatischen Erkrankungen verfügen über einen natürlichen Bewegungsdrang, dessen Einschränkung mit negativen Folgen für Lebensqualität und Krankheitsverlauf einhergehen kann. Bewegung ist heute ein unverzichtbarer Bestandteil der multidisziplinären Versorgung bei Kinderrheuma. Studien belegen zunehmend positive Effekte körperlich-sportlicher Aktivität auf Schmerzverarbeitung, Muskelkraft, kardiometabolische Risikofaktoren und psychosoziales Wohlbefinden. Dennoch zeigen viele Betroffene ein inaktives Bewegungsprofil mit umfangreichen Sitzzeiten und Schlafschwierigkeiten. Neue Forschungsperspektiven wie das 24-Stunden-Zeitnutzungsparadigma erweitern den Blick auf alltägliche Bewegungsmuster und machen auch niedrigschwellige Aktivitäten therapeutisch nutzbar.

Children and adolescents with juvenile idiopathic arthritis (JIA) are at increased risk for long-term physical and psychosocial complications, making physical activity (PA) and sedentary behaviour (SB) key modifiable lifestyle factors. Although increasingly acknowledged as relevant, data on the daily distribution of these behaviours in JIA remain scarce. This study aimed to (1) describe the time-use composition of SB and PA intensities in young people with JIA, (2) identify correlates of greater relative time spent in SB, and (3) compare movement behaviour patterns to matched population controls using a compositional data analysis (CoDA) approach. Patients aged 10–20 years with JIA and individually matched population controls wore hip-worn accelerometers (ActiGraph wGT3X-BT) for eight consecutive days. Movement behaviours were categorized into SB, light-intensity PA, and moderate-to-vigorous PA (MVPA) using validated, age-specific cut-points. CoDA with log-ratio transformations was used to model associations and compare groups. Diifferences in movement composition were assessed using adjusted multivariate analysis of variance (MANOVA). Data from 126 matched pairs (mean age: 15.0 ± 2.1 years; 67% female) were analysed. Patients spent, on average, 86% of waking time in SB, 8% in light-intensity PA, and 6% in MVPA. Overall, 76% did not meet the WHO recommendation of an average of ≥ 60 min of MVPA per day. Among those who did, 87% still spent ≥ 75% of their wear time sedentary. A greater proportion of SB relative to PA was associated with female gender (B = 0.13; p = 0.042), higher age (B = 0.06; p < 0.001), and higher BMI (B = 0.01; p = 0.049). Compared to controls, patients spent more time in SB, less in light-intensity PA, and slightly more in vigorous PA (all p < 0.001). Group differences remained significant after adjustment and were consistent across weekdays and weekends. Young people with well-controlled JIA show a distinctly unbalanced movement behaviour composition compared to controls, marked by a predominance of sedentary behaviour—even among those meeting PA guidelines. This highlights the limitations of threshold-based definitions and underscores the importance of assessing full daily movement patterns. Promoting light-intensity PA may offer a feasible strategy to reduce sedentary time, particularly in girls, older adolescents, and individuals with higher BMI. The study was registered in the German Clinical Trials Register (DRKS00022258).

Abstract Sjögren’s syndrome (SS) is a chronic autoimmune disease in which inflammatory cells infiltrate the exocrine glands, reducing glandular secretory function and ultimately resulting in keratoconjunctivitis sicca (dry eyes) and xerostomia (oral dryness). Cardiovascular risk factors are more prevalent in patients with SS than in healthy controls; patients with SS and metabolic syndrome also have higher leptin and inflammatory cytokine levels. In this study, we investigated the effects of HGR4113, a structural analog of glabridin that promotes mitochondrial function and is in clinical trials for obesity treatment, on the development of Sjögren’s syndrome in non-obese diabetic NOD/ShiLtJ (NOD) mice. HGR4113 inhibited IL-17 production by regulating STAT3 activity and the metabolic profile of splenic CD4 + T cells; it also increased the frequency of IL-10-producing regulatory B cells and decreased immunoglobulin production. Oral administration of HGR4113 (100 mg/kg) improved salivary flow rate, reduced lymphocyte infiltration, and lowered inflammatory cytokine levels in the salivary glands of NOD mice. HGR4113 also decreased the frequencies of splenic IL-17-producing T and B cells, germinal center B cells, and plasma cells ex vivo in NOD mice. Additionally, organoid formation from salivary gland stem cells of HGR4113-treated NOD mice increased, as did the levels of E-cadherin-14, aquaporin-5, α-SMA, and cytokeratin-14. Finally, treatment with HGR4113 promoted salivary gland organoid formation in vitro . HGR4113 improves salivary gland hypofunction by inhibiting lymphocyte infiltration and inflammation in the salivary glands and restoring damaged salivary tissue in SS-like NOD mice.

Zusammenfassung Die Prognose der juvenilen idiopathischen Arthritis (JIA) hat sich durch die Anwendung neuer Therapiestrategien und moderner Antirheumatika erheblich verbessert. Viele Patienten erreichen heute eine langanhaltende Remission, was die Frage nach einem möglichen Absetzen der Therapie aufwirft. In der klinischen Praxis variiert das Vorgehen beim Absetzen von krankheitsmodifizierenden Antirheumatika erheblich. Dabei spielen Faktoren wie die spezifische Form der JIA, das initiale Therapieansprechen, das Vorhandensein von Krankheitsschäden sowie die Präferenzen von Patienten und Familien eine Rolle. Dieser Übersichtsbeitrag stellt die aktuelle Evidenz zur Therapiedeeskalation bei der JIA vor. Es werden relevante Studien und Prädiktoren für ein erfolgreiches Absetzen der Therapie diskutiert. Zudem werden Strategien zur Erreichung einer medikamentenfreien Remission erörtert, einschließlich der potenziellen Rolle von Biomarkern und bildgebenden Verfahren. Basierend auf den vorhandenen, wenngleich noch begrenzten, Erkenntnissen werden Hinweise für den klinischen Alltag formuliert.

IntroductionThis is an interim analysis of the long-term effectiveness and safety of canakinumab in the tumor necrosis factor receptor-associated periodic syndrome (TRAPS) cohort of the RELIANCE non-interventional study.MethodsFrom June 2018, the RELIANCE non-interventional study enrolled paediatric (aged ≥ 2 – < 18 years) and adult patients (aged ≥ 18 years) with TRAPS who were receiving canakinumab as part of their routine medical care. Physician- and patient-reported measures of disease activity, dosing patterns and safety were evaluated at baseline and every 6 months until the end-of-study visit.ResultsA total of 21 patients with TRAPS were enrolled by the analysis cut-off date of December 2022, of which 61.9% (13/21) were paediatric patients (< 18 years) and 66.7% (14/21) were female. All patients were pre-treated with canakinumab prior to enrolment (median duration of canakinumab treatment prior to study inclusion: 1.2 years). Disease activity, evaluated by physician-reported (physician’s global assessment, disease remission, C-reactive protein, serum amyloid A) and patient-reported (disease activity, fatigue, impact on social life, autoinflammatory disease activity index diary) measures, was generally well controlled throughout the study. At baseline, the majority of patients (71.4%) were receiving the recommended starting dose (SD) of canakinumab, with a more even distribution between the < SD, SD, and > SD dosing schedules observed from month 6. No serious adverse drug reactions were reported. Patients continued to receive vaccinations during long-term treatment with canakinumab. In total, 85.7% (18/21) of patients met the Eurofever/PRINTO classification criteria for TRAPS, 42.9% (9/21) with the presence of a confirmative TNFRSF1A genotype and 42.9% (9/21) without. In total, 14.3% (3/21) of patients did not meet the classification criteria.ConclusionsData from this interim analysis support the long-term effectiveness and safety of canakinumab for the treatment of TRAPS.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40744-025-00809-y.

Plasma cells (PC) participate in the pathogenesis of systemic lupus erythematosus (SLE) through sustained autoantibody and inflammatory cytokine secretion. Current PC-depleting therapies risk eliminating protective long-lived PCs, highlighting the need to identify pathogenic subsets for selective targeting. Here, using single-cell RNA sequencing, B cell receptor repertoire analysis, and genetic models, we identify disease- and organ-specific PCs in lupus-prone mice. We find a substantial expansion of autoreactive CD19– PCs, particularly class-switched CXCR3⁺ and phosphatidylcholine-specific B-1–derived subsets, which exhibit unique gene expression profiles. We show that CD19– PCs originate from CD19+ PCs in a unidirectional manner. Peripheral blood from SLE patients shows elevated frequencies of CD19– PCs, implicating these cells in sustaining pathogenic activity. Our findings highlight the emergence of autoreactive CD19– PCs as a critical feature of lupus pathogenesis in mice and underscore the need for therapeutic approaches that extend beyond CD19-targeting to improve treatment strategies in SLE.

T helper (Th) cell lineages are linked to metabolism, but precise mechanisms in human Th1 cells remain unclear. We addressed this question by in vitro stimulation and CRISPR/Cas9-mediated gene editing. Metabolic profiling revealed enhanced glycolytic activity in Th1 versus non-polarized cells, evidenced by increased extracellular acidification rate, ATP production via glycolysis, lactate secretion, NADH abundance, and elevated glycolysis-dependent anabolic activity. Inhibition of glycolysis reduced IFNγ production and STAT1 phosphorylation independent of JAK1/2 or SHP2 activity and STAT1 abundance, implicating glycolysis directly in sustaining STAT1-mediated Th1 functionality. O-glycosylation of STAT1 via O-glycosyltransferase was pivotal in modulating STAT1 activity. Pharmaceutical O-glycosyltransfer-ase inhibition prevented Th1 differentiation as well as STAT1 O-glycosylation. CRISPR/Cas9 mediated mutation of the O-glycosylation Ser499 and Thr510 sites diminished STAT1 Ser727 phosphorylation and IFNγ synthesis. Together, this study highlights glycolysis as key regulator of human Th1 cell identity and effector function, with STAT1 O-glycosylation selectively maintaining Th1 effector capacity. This mechanism could be explored to safeguard Th1 cells.