A specific molecular profiling of secreted rheumatoid factors in Sjögren’ s disease patients with lymphoma

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ID: 328758
2026
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Abstract
Abstract Objective To perform proteomic analysis of secreted IgM-Rheumatoid factor (RF) in patients with Sjogren’s disease (SjD) with and without lymphoma to determine if a specific RF molecular profile is associated with lymphoma occurrence. Methods We studied 23 RF+ SjD patients from the ASSESS cohort. Eleven had lymphoma (cases), including five collected prior to lymphoma diagnosis (pre-lymphoma), and twelve had no lymphoma (controls). Cases and controls were matched for age and gender. Serum RF heavy chains were purified and analyzed using de novo mass spectrometry and database matching. IGHV subfamilies were identified, and amino acid sequences compared between cases and controls. Full RF sequences were used for structural modeling and affinity prediction. Results We observed a progressive enrichment of detectable immunoglobulin heavy chain variable region (VH) subfamilies among circulating RFs, with over-representation of VH1-69 RFs in SjD patients with lymphoma compared to those without lymphoma. We observed fewer somatic mutations in VH 1-69 RFs from pre lymphoma SjD patients whilst IGHV3 family RFs contained a greater number of unique mutations. Focused on VH 1-69s, we identified convergence of mutations amongst all patients and identified less frequent antigen-interacting mutations in pre lymphoma patients. Conclusion This study suggests changes in the serum RF antibody repertoire in SjD patients prior to and following lymphoma diagnosis, offering new insights into the serum clonal dynamics of the disease. Compositional changes in circulating RF clones may warrant further investigation in larger, independent cohorts to assess their potential value as a predictive biomarker for lymphoma.
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Authors Jing Jing Wang, Alexander Troelnikov, Bridie Armour, 滕彩珠, Tim Chataway, Véronique le Guern, Eric Hachulla, Valérie Devauchelle-Pensec, C. Larroche, Jacques-Eric Gottenberg, Xavier Mariette, Gaëtane Nocturne
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Journal Lara D. Veeken
Year 2026
DOI
10.1093/rheumatology/keag509
URL
https://doi.org/10.1093/rheumatology/keag509
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