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Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse
  1. Alexis Mathian1,
  2. Suzanne Mouries-Martin2,
  3. Karim Dorgham3,
  4. Hervé Devilliers4,
  5. Hans Yssel3,
  6. Laura Garrido Castillo3,
  7. Fleur Cohen-Aubart1,
  8. Julien Haroche1,
  9. Miguel Hié1,
  10. Marc Pineton de Chambrun1,
  11. Makoto Miyara3,
  12. Micheline Pha1,
  13. Flore Rozenberg5,
  14. Guy Gorochov3,
  15. Zahir Amoura1
  1. 1 Sorbonne Université, Assistance Publique–Hôpitaux de Paris, Groupement Hospitalier Pitié–Salpêtrière, French National Referral Center for Systemic Lupus Erythematosus, Antiphospholipid Antibody Syndrome and Other Autoimmune Disorders, Service de Médecine Interne 2, Institut E3M, Inserm UMRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Paris, France
  2. 2 Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, service de médecine interne et maladies systémiques (médecine interne 2), Dijon, France
  3. 3 Sorbonne Université, Inserm UMRS, Centre d’Immunologie et des Maladies Infectieuses (CIMI-Paris), Assistance Publique–Hôpitaux de Paris, Groupement Hospitalier Pitié–Salpêtrière, Département d’Immunologie, Paris, France
  4. 4 Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, service de médecine interne et maladies systémiques (médecine interne 2) et Centre d’Investigation Clinique, Inserm CIC 1432, Dijon, France
  5. 5 Université de Paris, Assistance Publique–Hôpitaux de Paris, Hôpital Cochin, Service de Virologie, Paris, France
  1. Correspondence to Dr Alexis Mathian, Internal Medicine, Pitié-Salpêtrière Hospital, Paris 75013, France; alexis.mathian{at}


Objectives Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.

Methods A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.

Results Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.

Conclusion Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.

  • systemic lupus erythematosus
  • interferon-alpha
  • remission
  • low disease activity
  • biomarker
  • relapse
  • flare

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  • Handling editor Josef S Smolen

  • AM, SM-M and KD contributed equally.

  • GG and ZA contributed equally.

  • Correction notice This article has been corrected since it published Online First. Figure one has been corrrected.

  • Contributors SM-M, AM, HD, KD, HY, GG, FR and ZA contributed to the conception and design of the study; SM-M, AM, KD, FC-A, JH, MH, MM, MP, FR and ZA were involved in the acquisition of data; SM-M, AM, HD, KD, HY, MPdC, GG, FR and ZA contributed to the analysis and interpretation of data. All authors contributed to drafting and/or revising the manuscript.

  • Funding Assistance Publique–Hôpitaux de Paris, Institut National de la Santé et de la Recherche Médicale (Inserm), Sorbonne Université, the French Arthritis Foundation, the Société Nationale Française de Médecine Interne and The Fondation pour la Recherche Médicale.

  • Competing interests None declared.

  • Patient consent for publication Informed consent was obtained from all the participants.

  • Ethics approval The local Ethics Committee of the Pitié-Salpêtrière Hospital approved this study.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available upon reasonable request.