REVIEW article
Front. Lupus
Sec. Clinical Research and Treatment in Lupus
Volume 3 - 2025 | doi: 10.3389/flupu.2025.1600768
This article is part of the Research TopicExploring Autoantibody Roles in Co-occurring SLE and Sjögren’s DiseaseView all articles
Sjögren's Disease and Systemic Lupus Erythematosus Overlap: Immunological Insights and Therapeutic Implications Authors
Provisionally accepted
- 1Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Tuscany, Italy
- 2Department of Clinical and Translational Science, University of Pisa, Pisa, Tuscany, Italy
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Sjögren's disease (SjD) and systemic lupus erythematosus (SLE) are distinct autoimmune disorders and their clinical overlap presents a unique immunological entity with specific challenges. While the clinical manifestations of the SjD-SLE overlap have been extensively characterised, its underlying pathogenetic mechanisms remain less understood. This review underscores the immunological features of the overlap, highlighting the roles of genetic predisposition, interferon pathway activation and B-cell dysregulation. Key genetic factors, particularly those associated with HLA and cytokine signaling, underpin disease susceptibility by promoting aberrant immune responses. The consequent and persistent interferon pathway activation drives chronic inflammation and establishes a feedback loop with autoantibody production. Furthermore, Extrafollicular B-cell responses are central to generating hallmark autoantibodies, such as anti-dsDNA and rheumatoid factor, which are frequent in the overlap. Finally, the continuous activation of interferons and B-cells not only increase disease activity but also contributes to lymphoproliferative complications. Despite progress in elucidating these mechanisms, patients with SjD-SLE overlap remain underrepresented in clinical trials, limiting therapeutic advancements. Emerging strategies, including interferon receptor inhibitors, BAFFblocking antibodies, and advanced B-cell depletion therapies, may offer promising options to hit the distinct immunological abnormalities of these patients.
Keywords: Sjögren's disease, systemic lupus erythematosus, Overlap syndrome, genetic predisposition, Interferon pathway, B-cell activation, Extrafollicular B-cell response, targeted therapy
Received: 26 Mar 2025; Accepted: 12 Aug 2025.
Copyright: © 2025 Fulvio, La Rocca, Tani, Mosca and Baldini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Giovanni Fulvio, Rheumatology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 56126, Tuscany, Italy
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