Zusammenfassung Die autologe hämatopoetische Stammzelltransplantation (aHSCT) hat sich als effektive Therapieoption für selektionierte Patienten mit schweren, therapieresistenten Autoimmunerkrankungen etabliert. Ziel der Therapie ist ein „immunologischer Reset“ durch eine hochdosierte Chemotherapie mit anschließender Rekonstitution des Immunsystems. Die beste Evidenz besteht für die hochaktive schubförmig-remittierende Multiple Sklerose sowie für die diffuse kutane systemische Sklerose, bei denen randomisierte Studien und Registerdaten eine signifikante Reduktion der Krankheitsaktivität und eine Verbesserung des progressionsfreien Überlebens zeigen. Die aktuellen Empfehlungen der European Society for Blood and Marrow Transplantation (EBMT) betonen die Bedeutung einer sorgfältigen Patientenselektion und Durchführung in spezialisierten Zentren. Neue zelluläre Therapien wie die CAR-T-Zelltherapie zeigen vielversprechende Ergebnisse und könnten zukünftig eine Alternative darstellen, sofern sie sich in aussagekräftigen Studien und in der Langzeitbeobachtung bewähren.
Die optimale Behandlungsstrategie bei Psoriasis-Arthritis (PsA) ist nach wie vor unbekannt. Aktuelle Leitlinien empfehlen einen stufenweisen Ansatz mit Methotrexat oder anderen konventionellen synthetischen (s) DMARDs, bevor Biologika oder zielgerichtete sDMARDs in Betracht gezogen werden. De Marco et al. untersuchten die Kombination aus Methotrexat und Golimumab gegen & uuml;ber Methotrexat und Kortikosteroiden zur PsA-Behandlung.
Genetic diagnostic testing has become highly relevant in pediatric rheumatology, but also in other pediatric subspecialties and in adult rheumatology. Early-onset, familial, atypical, or treatment-refractory inflammatory rheumatic diseases are now key scenarios in which a monogenic cause should be actively investigated. Acronyms such as ELVIS, GARFIELD, and FLASHBACKS help to structure these clinical suspicion patterns. Modern sequencing technologies - ranging from targeted gene panels to exome and genome sequencing - enable the identification of disease-causing variants across an increasingly broad spectrum. However, diagnostic success still depends heavily on precise phenotyping, structured transfer of clinical data to clinical genetics, Human Phenotype Ontology (HPO)-based filtering, and rigorous interpretation according to the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). Variants of uncertain significance require clinicogenetic correlation, functional follow-up when available, and often reanalysis. Beyond classical autoinflammatory diseases, inborn errors of immunity (IEI) are increasingly coming into focus as they may present primarily with arthritis, vasculitis, lupus-like disease, hyperinflammation, and multisystem inflammation. Particularly relevant for pediatric rheumatology are disorders associated with LACC1, COPA, and PMVK, complement defects and interferonopathies in monogenic lupus, DADA2, and the recently characterised SOCS1 insufficiency. The latter links rheumatology, immune dysregulation, and atopy in a characteristic manner and demonstrates incomplete penetrance in cohort data as well as a promising response to JAK inhibition. Genetic testing does not replace clinical expertise but substantially augments it and forms the basis of an increasingly personalized approach to pediatric rheumatology.
In contrast to juvenile idiopathic arthritis (JIA), it is primarily diseases in the category of collagenoses - most notably juvenile systemic lupus erythematosus (jSLE) - that might cause severe organ dysfunction and result in increased morbidity and mortality. B-cell dysregulation and the detection of specific autoantibodies are typical hallmarks of these diseases. Pediatric patients suffering from these potentially progressive and severe rheumatic diseases often require lifelong, and in certain cases high-dose, immunosuppressive therapy, which in turn is associated with significant long-term toxicity. Recent therapeutic approaches using chimeric antigen receptor (CAR) T-cells, originally developed for the treatment of oncological diseases, offer the possibility of more effectively depleting B cells in deeper tissues and thus potentially reducing or halting the altered immune activation. This review will discuss promising initial study results from this novel cellular therapy in adult medicine, as well as case reports from pediatric rheumatology, and will explore future developments in the use of CAR T-cells to treat children with severe autoimmune diseases. In addition to CAR T-cell therapy, this article also provides an overview of the application of further developments in this therapeutic approach, including the use of bispecific antibodies.
Objective Most RA-ILD biomarker studies enroll patients receiving treatment, which may alter inflammatory activity. We investigated whether calprotectin, sialic acid, and pannexin-1 show treatment-adjusted cross-sectional associations with ILD status in patients receiving treatment for RA. Methods This cross-sectional case-control study included 154 participants (49 patients with HRCT-confirmed RA-ILD, 55 RA patients without ILD, 50 healthy controls). Serum biomarkers were measured by ELISA. The primary multivariate logistic regression model for ILD status within the RA cohort was adjusted for age, sex, smoking status, and binary biologic DMARD and corticosteroid use, with VIF, L1/L2 penalized, parsimonious model, rituximab-exclusion resampling, and bootstrap-CI ROC sensitivity analyses. Results In Bonferroni-corrected pairwise testing between RA-ILD and RA without ILD, no biomarker reached p<0.017 (ESR p=0.97, CRP p=0.72, calprotectin p=0.092, sialic acid p=0.90, pannexin-1 p=0.066). After adjustment, three biomarkers showed independent associations with ILD: lower calprotectin (OR=0.21, 95% CI 0.08-0.57, p=0.002, q=0.006), higher age-adjusted sialic acid (OR=2.57, 1.22-5.45, p=0.013, q=0.020), and lower pannexin-1 (OR=0.52, 0.28-0.94, p=0.029, q=0.029). All VIFs were below 1.25; Ridge and Lasso regression retained the same three biomarkers. AUCs were modest, with all five 95% CIs including 0.50 (pannexin-1 0.61; calprotectin 0.60). Conclusion These findings indicate that serum calprotectin, sialic acid, and pannexin-1 carry weak conditional associations with ILD status in patients receiving RA treatment. However, their discriminatory performance is insufficient for standalone clinical use.
