December 2024 to March 2025
Authors: Valentina Pucino and Jacob Koopman
A Phase-3 Study on the Efficacy and Safety of Obinutuzumab in Active Lupus Nephritis
Furie R, et al. (doi:10.1056/NEJMoa2410965) conducted a phase-3 randomised double-blind placebo-controlled trial including 271 patients with actively proliferating lupus nephritis to study the efficacy and safety of obinutuzumab added to mycophenolate mofetil and glucocorticoids. Obinutuzumab is a humanized anti-CD20 monoclonal antibody that depletes B-cells better than other anti-CD20 antibodies. Confirming the results of the phase-2 NOBILITY trial, obinutuzumab led to complete renal response in 46%, as compared to 33% in the placebo group after 76 weeks. Serious adverse events were more common with obinutuzumab (32% vs 18%), consisting of mostly infections.
A Phase 3 Trial on the Efficacy and Safety of Upadacitinib in Giant-Cell Arteritis
Blockmans D, et al. (doi:10.1056/NEJMoa2413449) conducted a phase 3 randomised double-blind placebo-controlled trial including 428 patients with new-onset or relapsing giant-cell arteritis to study the efficacy and safety of upadacitinib added to glucocorticoids. Upadacitinib is a JAK1 inhibitor that blocks the IL-6 and IFNγ pathways. Upadacitinib led to sustained remission in 46% as compared to 29% in the placebo group after one year. Serious adverse events – including major cardiovascular or thrombo-embolic events – were similarly common, while infections were less common.
Synovial tissue myeloid dendritic cell subsets exhibit distinct tissue-niche localization and function in health and rheumatoid arthritis
MacDonald L, et al. (doi:10.1016/j.immuni.2024.11.004) identified distinct dendritic cell subsets with non-overlapping functions in synovial tissue taken from RA patients at different stage of diseases. Specifically, by using single-cell and spatial transcriptomics platforms they identified: 1) Tolerogenic AXL+ dendritic cells (DC)2s in healthy tissue. 2) Inflammatory DC3s and CCR7+ DC2s, which drive effector T cells and promote synovitis in active RA. Interestingly tissue taken from RA in remission did not display inflammatory DCs, but lacked the presence of tolerogenic DC. Targeting pathogenic DC3s or restoring tolerogenic DC2s may help restore immune homeostasis in RA joints.
Molecular and spatial analysis of tertiary lymphoid structures in Sjögren’s syndrome
Nayar S, et al. (doi:10.1038/s41467-024-54686-0) dissected the role of tertiary lymphoid structures in Sjögren’s syndrome. By combining single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjögren’s syndrome and sicca syndrome, they constructed a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures using ex-vivo functional studies. They identified a pericyte/mural cell with potential immunological functions.
Valentina Pucino
Valentina is an assistant professor and consultant in ImmunoRheumatology at University of Pisa (Italy) and honorary fellow at the Universities of Oxford and Birmingham (UK). Valentina’s research interest is focused on understanding the underlying mechanisms driving immune-mediated rheumatic disorders, with a particular focus on immunometabolism, alongside clinical practice. Valentina is a member of the Italian Societies of Rheumatology (SIR) and Immunology (SIICA), the British Society of Immunology, the British Society of Rheumatology and the European Academy of Allergy and Clinical Immunology (EAACI). She is an associate editor for Frontiers Immunology and Inflammation (Springer Nature). She is a member of the EMEUNET social media sub-committee.
Jacob Koopman
Jacob is a medical specialist in internal medicine and clinical immunology, working at Erasmus Medical Center in Rotterdam. In his clinical work and research, he focuses on systemic lupus erythematosus and antiphospholipid syndrome, particularly the prediction of these diseases before they become overt. He cares for patients with any other systemic immunological disease. He is a member of the Dutch Society of Allergy and Clinical Immunology and of EULAR. He is an editor for the Dutch Journal of Asthma, Allergy and Clinical Immunology. He is a member of the EMEUNET Newsletter subcommittee.