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Basic and translational research
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Germline variation of TNFAIP3 in primary Sjögren's syndrome-associated lymphoma
  1. Gaetane Nocturne1,
  2. Jessica Tarn2,
  3. Saida Boudaoud1,
  4. James Locke2,
  5. Corinne Miceli-Richard1,3,
  6. Eric Hachulla4,
  7. Jean-Jacques Dubost5,
  8. Simon Bowman6,
  9. Jacques-Eric Gottenberg7,
  10. Lindsey A Criswell8,
  11. Christopher J Lessard9,
  12. Kathy L Sivils9,
  13. Raphael Carapito10,11,
  14. Siamak Bahram11,
  15. Raphaèle Seror1,
  16. Wan-Fai Ng2,
  17. Xavier Mariette12
  1. 1INSERM UMR1184, CEA-iMETI/Division of Immuno-Virology, Université Paris Sud, Le Kremlin—Bicêtree, France
  2. 2Institute of Cellular Medicine and NIHR Biomedical Research Centre for Ageing and Chronic Diseases, Newcastle, UK
  3. 3Department of Rhumatologie, Hopital Bicetre, Le Kremlin Bicêtre, France
  4. 4Service de Médecine Interne, Lille, France
  5. 5Department of Rhumatologie, Hôpital, Clermont Ferrand, France
  6. 6Department of Rheumatology, University Hospitals Birmingham, Birmingham, UK
  7. 7Department of Rheumatology, University Hospital of Strasbourg, Strasbourg, France
  8. 8Department of Medicine, University of California, San Francisco, San Francisco, California, USA
  9. 9Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, USA
  10. 10U1109, INSERM and University of Strasbourg, Strasbourg, France
  11. 11Immunorhumatologie moléculaire, INSERM UMR S_1109, Centre de Recherche en Immunologie et Hématologie, Faculté de Médecine, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France and Service de Rhumatologie, Centre National de Référence pour les Maladies Systémiques Autoimmunes Rares, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
  12. 12Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Sud, Le Kremlin—Bicêtre, France
  1. Correspondence to Dr Xavier Mariette, Assistance Publique-Hôpitaux de Paris, Hôpitaux Universitaires Paris Sud, 78 rue du général Leclerc, Le Kremlin—Bicêtre 94275, France; xavier.mariette{at}bct.aphp.fr

Abstract

Background and objective A germline and coding polymorphism (rs2230926) of TNFAIP3 (A20), a central gatekeeper of nuclear factor-kappa B (NF-kB) activation, was recently found associated with primary Sjögren's syndrome (pSS)-associated lymphoma in a French cohort. We aimed to replicate this association.

Patients and methods The rs2230926 polymorphism was genotyped in cases and controls of European ancestry from two independent cohorts from UK and France. Case control association tests were performed (Fisher's test) in the two cohorts, followed by a meta-analysis of the two cohorts.

Results The UK cohort included 308 controls and 590 patients with pSS including 31 with a history of lymphoma. The French cohort consisted of 448 controls and 589 patients with pSS including 47 with lymphoma. In both cohorts, the rs2230926 missense polymorphism was not associated with pSS. However, in the UK cohort, the rs2230926G variant was significantly associated with pSS-associated lymphoma (OR=2.74, 95% CI (1.07 to 7.03), p=0.0423, compared with patients with pSS without lymphoma, and OR=3.12, 95% CI (1.16 to 8.41), p=0.0314, compared with healthy controls) as observed in the French cohort. The meta-analysis of the two cohorts confirmed these results (OR=2.48, 95% CI (1.87 to 3.28) p=0.0037 and OR=2.60, 95% CI (1.91 to 3.53) p=0.0031, respectively).

Conclusions This study confirms the role of A20 impairment in pSS-associated lymphoma. Subtle germline abnormalities of genes leading to impaired control of NF-kB activation in B cells continuously stimulated by autoimmunity enhance the risk of lymphoma.

  • Sjøgren's Syndrome
  • B cells
  • Autoimmunity

https://doi.org/10.1136/annrheumdis-2015-207731

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