Association between anti-cytosolic 5'-nucleotidase 1A (anti-cN1A) antibodies and lymphoma in primary Sjögren Disease (SD)

Pierre-Marie Duret¹, Maude Bouchard-Marmen², Loukas Chatzis³, Margherita Giannini⁴, François Severac⁵, FELTEN Renaud⁶, Dan Levy⁷, Benoit Nespola⁸, Emmanuel Chatelus⁹, Emmanuelle Dernis¹⁰, Valerie Devauchelle¹¹, Philippe Dieude¹², Jean-Jacques Dubost¹³, Anne-Laure Fauchais¹⁴, Bernard Geny¹⁵, Eric Hachulla¹⁶, Claire larroche¹⁷, Véronique Le Guern¹⁸, Jacques Morel¹⁹, Aleth Perdriger²⁰, Carine Salliot²¹, Alain SARAUX²², Damien Sène²³, Jean Sibilia²⁴, SORDET Christelle⁶, Olivier Vittecoq²⁵, Raphaele Seror²⁶, Gaetane Nocturne²⁷, Andreas Goules²⁸, Athanasios G. Tzioufas²⁹, Xavier Mariette³⁰, Jacques-eric GOTTENBERG³¹ and Alain Meyer³², ¹Colmar General Hospital; Strasbourg University Hospital, Strasbourg, France, ²CHU de Québec, Québec, QC, Canada, ³Pathophysiology Department, Athens School of Medicine, National and Kapodistrian University of Athens, Greece, Athens, Greece, ⁴Explorations fonctionnelles musculaires, Service de physiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, Service de Rhumatologie, Centre de référence des maladies auto-immunes rares (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, Strasbourg, Alsace, France, ⁵Département de Santé Publique, Groupe Méthodes en Recherche Clinique (GMRC), CHU de Strasbourg, Strasbourg, Strasbourg, Alsace, France, ⁶Service de Rhumatologie, Centre de référence des maladies auto-immunes rares (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, Strasbourg, Alsace, France, ⁷Explorations fonctionnelles musculaires, Service de physiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, Strasbourg, Alsace, France, ⁸Laboratoire d’Immunologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, Strasbourg, Alsace, France, ⁹Department of Rheumatology, University Hospital Strasbourg, France, Strasbourg, France, ¹⁰Service de Rhumatologie, Centre Hospitalier Le Mans, Le Mans, Le Mans, France, ¹¹UBO, Brest, France, ¹²Service de Rhumatologie, Hôpital Bichat APHP, Paris, Paris, Ile-de-France, France, ¹³Service de Rhumatologie, CHU Gabriel Montpied, Clermont-Ferrand, Clermont-Ferrand, France, ¹⁴UR ³⁰⁷², Centre de Recherche en Biomédecine, Université de Strasbourg, Strasbourg; France, Strasbourg, France, ¹⁵UR ³⁰⁷², Centre de Recherche en Biomédecine, Université de Strasbourg, Strasbourg; FranceExplorations fonctionnelles musculaires, Service de physiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg;, Strasbourg, Alsace, France, ¹⁶Service de Médecine Interne et Immunologie Clinique, CHU de Lille, Hôpital Claude Huriez, Lille, Lille, France, ¹⁷Service de Médecine Interne, Hôpital Avicenne APHP, Bobigny, Paris, Ile-de-France, France, ¹⁸Cochin hospital, Paris, France, ¹⁹CHU and University of Montpellier, Montpellier, France, ²⁰Rennes University, Rennes, France, ²¹CHR orleans, Orleans, France, ²²CHU Brest, Brest, France, ²³Department of Internal Medicine, Lariboisière University Hospital, Université Paris Cité, Assistance Publique Hôpitaux de Paris, Paris, Ile-de-France, France, ²⁴Rheumatology Department, National Center for Rare autoimmune disease RESO,Strasbourg University Hospital, Strasbourg, Alsace, France, ²⁵Service de Rhumatologie & CIC-CRB ¹⁴⁰⁴, CHU de Rouen, Université de Rouen, Rouen, Rouen, France, ²⁶Department 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, ²⁷University Paris Saclay, Le Kremlin Bicetre, Ile-de-France, France, ²⁸Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens Institute for Autoimmune Systemic and Neurologic Diseases, Athens, Athens, Greece, ²⁹Department of Pathophysiology, School of Medicine, National and Kapodistrian University of Athens Institute for Autoimmune Systemic and Neurologic Diseases, Athens, Athens, ³⁰Université Paris-Saclay, Le Kremlin Bicetre, France, ³¹Hautepierre Hospital, STRASBOURG, Alsace, France, ³²Service de Rhumatologie, Centre de référence des maladies auto-immunes rares (RESO), Hôpitaux Universitaires de Strasbourg, Strasbourg, Explorations fonctionnelles musculaires, Service de physiologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, UR ³⁰⁷², Centre de Recherche en Biomédecine, Université de Strasbourg, Strasbourg; France, Strasbourg, Alsace, France

Meeting: ACR Convergence 2025

Keywords: Biomarkers, Cohort Study, Sjögren's syndrome

Session Information

Date: Sunday, October 26, 2025

Title: (0506–0521) Sjögren’s Disease – Basic & Clinical Science Poster I: Etiology, Pathogenesis, Diagnosis

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: There is an unmet clinical need for identification of novel biomarkers of systemic complications and lymphoma in primary Sjögren disease (SD). Anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) antibodies have been reported in SD but their clinical significance in this specific context is currently unknown. Anti-cN1A have been originally described in inclusion body myositis (IBM). Both SD and IBM are associated with hematological malignancies. The objectives of this study were to determine the clinical significance of anti-cN1A antibodies and their value as a predictive biomarker of non-Hodgkin lymphoma (NHL) in SD.

Methods: Baseline serum levels of anti-cN1A were measured in a prospective discovery cohort of 377 patients with SD, from the French ASSESS cohort, whose primary objective was to prospectively examine the incidence and predictors of systemic complications and lymphoma in SD. The significance of anti-cN1A positivity in the ASSESS cohort was analyzed in univariate and multivariate models. Multivariate analysis included variables associated with anti-cN1A positivity in univariate analyses with a p-value < 0.2. An independent validation case-control cohort of 58 SD patients (26 patients with untreated SD-NHL at the time of blood sampling and 32 patients with SD and no lymphoma despite ≥10-year follow-up), from the Athens’ University Hospital SD cohort, was also screened for anti-cN1A antibodies.

Results: Twenty-nine SD patients tested positive for anti-cN1A (29/377 [7.7 %] [95% CI: 0.05-0.11]). Only one patient in the anti-cN1A positive group was diagnosed with myositis during the follow-up, which fulfilled IBM criteria (1/29 [3.4 %] vs. 1/348 [0.3%] in the anti-cN1A negative group, p = 0.024). Anti-cN1A positive patients had more frequently lymphadenopathy at baseline (8/29 [27.6 %] vs. 44/346 [12.7 %], p = 0.026) and more frequently developed lymphoma during follow-up (incident NHL: 3/29 [10.3%] in the anti-cN1A positive vs. 6/348 [1.7%] in the anti-cN1A negative patients, p = 0.003). The association between SD-NHL and anti-cN1A positivity remained significant (p=0.008) in multivariate analysis taking into account some previously reported predictors of lymphoma including lymphadenopathy, beta2-microglobulin and BAFF serum levels.In the validation cohort, patients with SD-NHL had more frequently anti-cN1A positivity as compared with SD patients and no lymphoma (4/26 [12%] vs 0/32 [0%], p= 0.039).

Conclusion: In two independent cohorts of well-phenotyped SD patients, anti-cN1A positivity was associated with lymphoma. Anti-cN1A positivity might therefore represent a novel predictive biomarker of SD-related lymphoma.

Disclosures: P. Duret: None; M. Bouchard-Marmen: None; L. Chatzis: None; M. Giannini: None; F. Severac: None; F. Renaud: None; D. Levy: None; B. Nespola: None; E. Chatelus: None; E. Dernis: None; V. Devauchelle: None; P. Dieude: None; J. Dubost: None; A. Fauchais: None; B. Geny: None; E. Hachulla: None; C. larroche: None; V. Le Guern: AstraZeneca, 12, attending meetings and travel., Bristol-Myers Squibb(BMS), 6, Novartis, 2; J. Morel: AbbVie, 2, 5, 6, Biocon, 6, Biogen, 6, Boehringer Ingelheim, 2, Bristol Myers Squibb, 2, 5, 6, Fresenius Kabi, 2, 6, Galapagos, 2, 6, GlaxoSmithKline, 2, 6, Lilly, 2, 6, Medac, 6, Mylan/Viatris, 6, Nordic Pharma, 6, Novartis, 2, 5, 6, Pfizer, 5, 6, Roche/Chugai, 6, Sanofi, 2, 6; A. Perdriger: None; C. Salliot: None; A. SARAUX: Novartis, 6; D. Sène: None; J. Sibilia: None; S. Christelle: None; O. Vittecoq: None; R. Seror: Amgen, 6, Boehringer-Ingelheim, 2, Bristol-Myers Squibb(BMS), 2, GlaxoSmithKlein(GSK), 2, 6, Janssen, 2, Kiniska, 2, Novartis, 2, 6; G. Nocturne: None; A. Goules: None; A. Tzioufas: 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; A. Meyer: None.

To cite this abstract in AMA style:

Duret P, Bouchard-Marmen M, Chatzis L, Giannini M, Severac F, Renaud F, Levy D, Nespola B, Chatelus E, Dernis E, Devauchelle V, Dieude P, Dubost J, Fauchais A, Geny B, Hachulla E, larroche C, Le Guern V, Morel J, Perdriger A, Salliot C, SARAUX A, Sène D, Sibilia J, Christelle S, Vittecoq O, Seror R, Nocturne G, Goules A, Tzioufas A, Mariette X, GOTTENBERG J, Meyer A. Association between anti-cytosolic 5′-nucleotidase 1A (anti-cN1A) antibodies and lymphoma in primary Sjögren Disease (SD) [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/association-between-anti-cytosolic-5-nucleotidase-1a-anti-cn1a-antibodies-and-lymphoma-in-primary-sjogren-disease-sd/. Accessed .

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