Serum APRIL Is Associated With B-Cell Activation Markers, Disease Activity, and Lymphoma Risk in Sjögren Disease (SD): Data From the prospective ASSESS Cohort

Pierre-Marie Duret¹, Pascal Schneider², Ludivine Robin³, Marine Vierling⁴, Nicolas Meyer⁵, Valerie Devauchelle⁶, Divi Cornec⁷, Alain SARAUX⁸, Jean Sibilia⁹, Raphaele Seror¹⁰, Yann Nguyen¹¹, Gaetane Nocturne¹², Laurent Mauvieux¹³, Laurent Miguet¹⁴, Xavier Mariette¹⁵ and Jacques-eric GOTTENBERG¹⁶, ¹Colmar General Hospital; Strasbourg University Hospital, Strasbourg, France, ²Université de Lausanne,Département de biochimie, Lausanne, Switzerland, ³Strasbourg University Hospital, Department of pathology, ⁴CNRS, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Institut de Biologie Moléculaire et Cellulaire (IBMC), Strasbourg, France Strasbourg, France;, Strasbourg, Alsace, France, ⁴Strasbourg University Hospital, Department of Public Health, GMRC, Strasbourg, France,, Strasbourg, Alsace, France, ⁵Strasbourg University Hospital, Department of Public Health, GMRC, Strasbourg, France, Strasbourg, Alsace, France, ⁶UBO, Brest, France, ⁷LBAI, UMR¹²²⁷, University of Brest, CHU Brest, Brest, France, Brest, Bretagne, France, ⁸CHU Brest, Brest, France, ⁹Rheumatology Department, National Center for Rare autoimmune disease RESO,Strasbourg University Hospital, Strasbourg, Alsace, France, ¹⁰Department of Rheumatology, National referral center for auto immune disease and Sjogren disease, Université Paris-Saclay, INSERM UMR¹¹⁸⁴: Centre for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique-Hôpitaux de Paris, Hôpital Bicêtre, Le Kremlin Bicêtre, Paris, France., le kremlin bicetre, France, ¹¹Department of Internal Medicine, Beaujon Hospital, AP-HP Nord, Université Paris Cité, Clichy, France, Clichy, France, ¹²University Paris Saclay, Le Kremlin Bicetre, Ile-de-France, France, ¹³Strasbourg University Hospital, Laboratory hematology, Strasbourg, France,CNRS, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Institut de Biologie Moléculaire et Cellulaire (IBMC), Strasbourg, France, Strasbourg, Alsace, France, ¹⁴Strasbourg University Hospital, Laboratory hematology, Strasbourg, France, CNRS, Immunopathologie et Chimie Thérapeutique/Laboratory of Excellence Medalis, Institut de Biologie Moléculaire et Cellulaire (IBMC), Strasbourg, France, Strasbourg, Alsace, France, ¹⁵Université Paris-Saclay, Le Kremlin Bicetre, France, ¹⁶Hautepierre Hospital, STRASBOURG, Alsace, France

Meeting: ACR Convergence 2025

Keywords: B-Cell Targets, Biomarkers, Cohort Study, cytokines, Sjögren's syndrome

Session Information

Date: Monday, October 27, 2025

Title: Abstracts: Sjögren’s Disease – Basic & Clinical Science (1680–1685)

Session Type: Abstract Session

Session Time: 1:45PM-2:00PM

Background/Purpose: Sjögren disease (SD) is a B cell driven systemic auto-immune disease, with a need for biomarkers to better assess disease activity, risk of lymphoma and finding new therapeutic targets. While BAFF, a key B cell survival cytokine involved in precoce steps of B cell ontogeny, has been previously associated with systemic manifestations and lymphomagenesis in SD, data on a proliferation-inducing ligand (APRIL), another B cell cytokine acting in later stages of B cell ontogeny (e.g., plasmablasts and plasma cells via BCMA and TACI receptors), remain limited. This study aimed to investigate associations between APRIL, B cell biomarkers, disease activity and risk of lymphoma in SD.

Methods: Serum APRIL levels (ELISA, Invitrogen°) were assessed in 337 patients with SD from the French ASSESS cohort (17-year follow-up) and 40 healthy donors (HD). All patients met 2016 ACR/EULAR classification criteria. Patients were stratified according to the validated clustering of the ASSESS cohort: (C1) biologically active without systemic manifestations; (C2) systemic manifestations; (C3) low activity/high symptom burden; and SD-related lymphoma (incident n=9, prevalent n=16). The association between SD-related lymphoma, APRIL and lymphoma predictors at enrollment (clinESSDAI, ESSDAI, lymphocytopenia < 0.5 G/L, CD4/CD8 T cell ratio≤0.8, RF positivity, cryoglobulinemia, monoclonal component, and low C4) and other potential biomarkers (IgG levels, total gammaglobulins, immune-complexes, beta2microglobulin, kappa and lambda free light chains, quantitative [q] anti- SSA/SSB autoantibodies, digital interferon [IFN] alpha, s-FLT3, CXCL10, CCL19, CXCL13, BAFF), were analyzed in univariate and multivariate models. Multivariate analyses took into account APRIL and variables significantly associated with lymphoma in univariate analyses selected by a stepwise procedure. Estimation of incident lymphoma risk was assessed in a separate multivariate model.

Results: APRIL levels increased across subgroups: HD (0.36 ng/mL), cluster 3 (0.34), cluster 1 (0.97), cluster 2 (1.2), lymphoma (2.33), with highest levels in incident lymphoma (2.8; p< 0.0001). In multivariate analysis, including only markers significantly associated with lymphoma in univariate analyses, APRIL expression at enrollment remained significantly associated with lymphoma (OR 1.1; 95% CI [1- 1.17] p=0.045), along with BAFF levels (mean [SD]: 1085.1 pg/ml [742.4]; per 1000 BAFF units, OR 1.75; 95% CI [1.11-2.71]; p=0.0012), CD4/CD8 ratio ≤ 0.8 (OR 4.7 95% CI [1.13-18.03]; p=0.027), low C4 (OR 5.38 95% CI [1.89-16.04]; p=0.002), lymphopenia < 0.5 G/L (OR 51.02 95% CI [4.65-611.01]; p=0.001), glandular (OR 4.95 95% CI [1.49-15.97]; p=0.007), and adenopathy (OR 6.43 95% CI [1.1-31.8]; p=0.027) domains of the ESSDAI. In a separate multivariate model, APRIL (OR 1.1 95% CI [1.01-1.21]; p=0.02) and CXCL13 (OR 1.0 95% CI [1.0-1.0]; p=0.01) were found independently associated with the risk of developing incident lymphoma.

Conclusion: These results suggest the interest of APRIL, a B-cell cytokine easily measurable in patients’ sera, as a potential biomarker of SD-related lymphoma, and as a potentially relevant therapeutic target in SD.

Disclosures: P. Duret: None; P. Schneider: None; L. Robin: None; M. Vierling: None; N. Meyer: None; V. Devauchelle: None; D. Cornec: None; A. SARAUX: Novartis, 6; J. Sibilia: None; R. Seror: Amgen, 6, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, 6, Janssen, 2, Kiniska, 2, Novartis, 2, 6; Y. Nguyen: None; G. Nocturne: None; L. Mauvieux: None; L. Miguet: None; X. Mariette: Galapagos, 2, GlaxoSmithKlein(GSK), 2, Janssen, 2, Novartis, 2, Ose Pharmaceuticals, 5, Pfizer, 2, UCB, 2; J. GOTTENBERG: AbbVie/Abbott, 6, Bristol-Myers Squibb(BMS), 5, 6, CSL Behring, 6, Eli Lilly, 6, Galapagos, 6, Genzyme, 6, Gilead, 6, Merck/MSD, 6, Novartis, 6, Pfizer, 6, Roche, 6, Sanofi, 6.

To cite this abstract in AMA style:

Duret P, Schneider P, Robin L, Vierling M, Meyer N, Devauchelle V, Cornec D, SARAUX A, Sibilia J, Seror R, Nguyen Y, Nocturne G, Mauvieux L, Miguet L, Mariette X, GOTTENBERG J. Serum APRIL Is Associated With B-Cell Activation Markers, Disease Activity, and Lymphoma Risk in Sjögren Disease (SD): Data From the prospective ASSESS Cohort [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/serum-april-is-associated-with-b-cell-activation-markers-disease-activity-and-lymphoma-risk-in-sjogren-disease-sd-data-from-the-prospective-assess-cohort/. Accessed .

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/serum-april-is-associated-with-b-cell-activation-markers-disease-activity-and-lymphoma-risk-in-sjogren-disease-sd-data-from-the-prospective-assess-cohort/