Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: Sjögren’s syndrome (SjS) involves chronic inflammation of exocrine glands that can be complicated by extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT). We analyze the generation of the antinuclear (ANA) and rheumatoid factor (RF)-specific B cell repertoires, and their interaction in patient tissues before and at disease relapse after rituximab treatment.
Methods: We analyzed blood and tissues of 6 SjS patients with anti-Ro60, anti-Ro52, anti-La and RF autoantibodies. We analyzed the tissues of 2 patients that had been diagnosed with MALT lymphoma and were subsequently treated with rituximab monotherapy. We analyzed anti-Ro60, anti-Ro52, anti-La and RF clones using a combination of new, partly self-developed tools to analyze autoreactive B cell receptors at DNA, RNA, protein and single cell level.
Results: In affected tissues anti-Ro52, anti-La and anti-Ro60 clones outnumbered RF clones. Compared to ANA clones affinity maturation of RF clones was IgM directed and depended on the structural integrity of the frame work regions of preferred variable immunoglobulin segments. In MALT lymphoma tissues lymphomatous clones were solitary large RF clones using shared sequence motifs and displaying high intra-clonal diversification. These co-occurred with a high number of ANA clones. At clinical relapse after rituximab treatment dominant persistent MALT or other RF clones proliferated in a memory, intra-clonal diversification directed recall response. In the same tissues many small ANA clones displayed a plasma cell directed recall response.
Conclusion: We find divergent affinity maturation of RF compared to ANA clones, that exacerbates in RF-clone derived MALT lymphomas and at regeneration of disease manifestations after rituximab.
To cite this abstract in AMA style:Broeren M, Balzaretti G, Wang J, Groenen P, van Schaik B, Chataway T, Kaffa C, Bervoets S, Hebeda K, Bounova G, Pruijn G, Gordon T, De Vries N, Thurlings R. Maturation and Dysfunction of Autoreactive B Cell Clones in Tissues of Patients with Sjögren’s Syndrome [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 9). https://acrabstracts.org/abstract/maturation-and-dysfunction-of-autoreactive-b-cell-clones-in-tissues-of-patients-with-sjogrens-syndrome/. Accessed January 31, 2023.
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