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Frequency of tumour necrosis factor alpha receptor superfamily 1A multiple sclerosis-associated variants in patients with rheumatoid arthritis with anti-tumour necrosis factor therapy-related demyelinating complications
  1. Samuel Bitoun1,
  2. Corinne Miceli-Richard1,
  3. Céline Verstuyft2,
  4. Pierre Antoine Juge3,
  5. Philippe Dieudé3,
  6. Jean-Marie Berthelot4,
  7. Christophe Richez5,
  8. Cécile Cauquil6,
  9. Christelle Sordet7,
  10. Sylvie Melac-Ducamp8,
  11. Laure Gossec9,10,
  12. Beatrice Bouvard11,
  13. Emmanuelle Dernis12,
  14. Eric Houvenagel13,
  15. Marie-Astrid Boutry-Bacle14,
  16. Xavier Mariette1,
  17. Raphaèle Seror1
  1. 1 Department of Rheumatology, Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, INSERM U1184, Le Kremlin Bicêtre, France
  2. 2 Department of Pharmacogenetics, Hôpital de Bicètre, Le Kremlin Bicetre, France
  3. 3 Department of Rheumatology, CHU Bichat, Paris, France
  4. 4 Department of Rheumatology, C.H.U. Hôtel Dieu, Nantes, France
  5. 5 Department of Rheumatology, C.H.U Pellegrin, Bordeaux, France
  6. 6 Department of Neurology, Hopital de Bicètre, Le Kremlin Bicètre, France
  7. 7 Rhumatologie, C.H.R.U. Hôpitaux Universitaires Strasbourg, Strasbourg, France
  8. 8 Department of Rheumatology, C.H.I, Nevers, France
  9. 9 Sorbonne Universités, UPMC Univ Paris 06, GRC-08, Institut Pierre Louis d’Epidémiologie et de Santé Publique, Paris, France
  10. 10 Rheumatology Department, Pitie-Salpétrière Hospital, AP-HP, Paris, France
  11. 11 Department of Rheumatology, Centre Hospitalier Universitaire d’Angers, Angers, France
  12. 12 Department of Rheumatology, Centre Hospitalier du Mans, Le Mans, France
  13. 13 Department of Rheumatology, Hôpital Saint Philibert, Lomme, France
  14. 14 Department of Rheumatology Internal medicine, Centre Hospitalier, Abbeville, France
  1. Correspondence to Dr Raphaèle Seror, Université Paris-Sud, AP-HP, Hôpitaux Universitaires Paris-Sud, INSERM U1184, and Centre Hospitalier Universitaire de Bicêtre, Hôpital Bicêtre, Le Kremlin Bicêtre, France; raphaele.seror{at}aphp.fr

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Tumour necrosis factor alpha (TNFα) is a key cytokine in inflammatory rheumatic diseases but is also implicated in multiple sclerosis (MS) where TNFα is elevated in demyelinating plaques. However, TNFα inhibitors (TNFi) have opposite effects: they have revolutionised the treatment of chronic rheumatic diseases but may cause flares of MS.1 Several studies have suggested an association between TNFi use and occurrence of demyelinating disorders.2 3 Their incidence is estimated up to 4% after 18 months of treatment in a recent prospective study with systematic neurological examination before and after treatment initiation.4

In addition, two TNF receptor superfamily 1 (TNFRSF1A) single nucleotide polymorphisms, (SNPs) rs1800693 and rs4149584 (TNFRSF1A R92Q), have been shown to increase the risk of developing MS.5 The rs1800693*G allele leads to a dysfunctional TNFα soluble receptor that inhibits TNFα signalling.6 Rare variants of TNFRSF1A locus have also been implicated …

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