Annals of the rheumatic diseases · 2026
A genetic variant of BAFF is associated with the risk of lymphoma in Sjögren disease.
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Beydon Maxime, Dulin Marie, Ly Bineta, Verstuyft Céline, Cardoso Allison, Juge Pierre Antoine, Dieudé Philippe, Lessard Christopher J, Khatri Bhuwan, Radziszewski Marcin, Guern Véronique Le, Gottenberg Jacques Eric, Seror Raphaele, Mariette Xavier, Nocturne Gaetane
Аннотация
OBJECTIVES: B-cell activating factor (BAFF) of the Tumors Necrosis Factor (TNF) family is involved in the pathogenesis of Sjögren's disease (SjD). A functional variant (BAFF variant [BAFF-var]) of the BAFF gene (TNFSF13B), leading to increased levels of BAFF, has been described. The aim of this study was to investigate the association between BAFF-var and clinical phenotype and risk of SjD.
METHODS: A case-control study including cases from Paris Saclay and the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort and controls (blood donors from Etablissement Français du Sang [EFS]) was conducted. Genetic association analyses included only patients with European ancestry assessed by a principal component analysis using 24 ancestry-informative markers.
RESULTS: We included 770 cases (420 from Paris Saclay and 350 from ASSESS) and 786 controls from EFS. Among them, 666 cases and 721 controls were found of European ancestry. We found that BAFF-var was significantly associated with higher soluble BAFF (sBAFF) level (1392.7 vs 1107.0 pg/mL, P < .001), and with increased occurrence of lymphoma (13% in patients with SjD with BAFF-var vs 5.8% in patients with SjD with BAFF-WT (wild-type), P = .013). BAFF-var remained independently associated with lymphoma after adjustment for rheumatoid factor, sex, and cumulative European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (odds ratio [OR] 2.60, 95% CI: 1.14-5.47). By comparison with ancestry-matched controls, BAFF-var was also associated with SjD itself with a minor allele frequency of 0.061 in cases and 0.035 in controls (OR = 1.77, P = .0017).
CONCLUSIONS: We found an association between BAFF-var and sBAFF levels, occurrence of lymphoma as well as occurrence of SjD itself. This variant could be a new biomarker for lymphoma risk in SjD.
METHODS: A case-control study including cases from Paris Saclay and the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort and controls (blood donors from Etablissement Français du Sang [EFS]) was conducted. Genetic association analyses included only patients with European ancestry assessed by a principal component analysis using 24 ancestry-informative markers.
RESULTS: We included 770 cases (420 from Paris Saclay and 350 from ASSESS) and 786 controls from EFS. Among them, 666 cases and 721 controls were found of European ancestry. We found that BAFF-var was significantly associated with higher soluble BAFF (sBAFF) level (1392.7 vs 1107.0 pg/mL, P < .001), and with increased occurrence of lymphoma (13% in patients with SjD with BAFF-var vs 5.8% in patients with SjD with BAFF-WT (wild-type), P = .013). BAFF-var remained independently associated with lymphoma after adjustment for rheumatoid factor, sex, and cumulative European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (odds ratio [OR] 2.60, 95% CI: 1.14-5.47). By comparison with ancestry-matched controls, BAFF-var was also associated with SjD itself with a minor allele frequency of 0.061 in cases and 0.035 in controls (OR = 1.77, P = .0017).
CONCLUSIONS: We found an association between BAFF-var and sBAFF levels, occurrence of lymphoma as well as occurrence of SjD itself. This variant could be a new biomarker for lymphoma risk in SjD.