Alexis Mathian1, Suzanne Mouries-Martin2, Karim Dorgham3, Hervé Devilliers4, Laura Barnabei5, Elyès Ben Salah3, Fleur Cohen-Aubart1, Laura Garrido Castillo3, Julien Haroche1, Miguel Hie6, Marc Pineton de Chambrun6, Makoto Miyara3, Delphine Sterlin3, Micheline Pha6, Du Lê Thi Huong6, Frédéric Rieux-Laucat5, Flore Rozenberg7, Guy Gorochov3, Zahir Amoura1. 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. Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, Service de médecine interne et maladies systémiques (médecine interne 2), Dijon, France. 3. Sorbonne Université, Inserm UMRS, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), Assistance Publique-Hôpitaux de Paris, Groupement Hospitalier Pitié-Salpêtrière, Paris, France. 4. Centre Hospitalier Universitaire de Dijon, Hôpital François-Mitterrand, Service de médecine interne et maladies systémiques (médecine interne 2) and Centre d'Investigation Clinique, Inserm CIC 1432, Dijon, France. 5. Laboratory of Immunogenetics of Pediatric Autoimmune Diseases, INSERM UMR-Institut Imagine, Sorbonne Paris Cité, Paris, France. 6. 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, Paris, France. 7. Sorbonne Paris Cité, Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Service de Virologie, Paris, France.
Abstract
OBJECTIVE: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity. METHODS: IFNα concentrations in serum samples from 150 consecutive SLE patients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of <4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of >0), and into groups with no flare or mild/moderate flare or severe flare. RESULTS: Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLE patient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFNα concentrations and identifying patients with low disease activity. CONCLUSION: Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment.
OBJECTIVE: No simple or standardized assay is available to quantify interferon-α (IFNα) in routine clinical practice. Single-molecule array (Simoa) digital enzyme-linked immunosorbent assay (ELISA) technology enables direct IFNα quantification at attomolar (femtogram per milliliter [fg/ml]) concentrations. This study was undertaken to assess IFNα digital ELISA diagnostic performances to monitor systemic lupus erythematosus (SLE) activity. METHODS: IFNα concentrations in serum samples from 150 consecutive SLEpatients in a cross-sectional study were determined with digital ELISA and a functional biologic activity assay (bioassay). According to their Safety of Estrogens in Lupus Erythematosus National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) flare composite scores, patients were divided into groups with inactive SLE (SLEDAI score of <4 or clinical SLEDAI score of 0) or active SLE (SLEDAI score of ≥4 or clinical SLEDAI score of >0), and into groups with no flare or mild/moderate flare or severe flare. RESULTS: Based on serum samples from healthy blood donors, the abnormal serum IFNα level threshold value was 136 fg/ml. Next, using receiver operating characteristic curves for an SLEpatient series that was widely heterogeneous in terms of disease activity and organ involvement, the threshold IFNα value associated with active disease was determined to be 266 fg/ml. The digital ELISA-assessed serum IFNα level was a better biomarker of disease activity than the Farr assay because its specificity, likelihood ratio for positive results, and positive predictive value better discerned active SLE or flare from inactive disease. The digital ELISA was more sensitive than the bioassay for detecting low-abnormal serum IFNα concentrations and identifying patients with low disease activity. CONCLUSION: Direct serum IFNα determination with a highly sensitive assay might improve monitoring of clinical SLE activity and selection of the best candidates for anti-IFNα treatment.
Authors: A Paradowska-Gorycka; A Wajda; B Stypinska; E Walczuk; E Rzeszotarska; M Walczyk; E Haladyj; K Romanowska-Prochnicka; A Felis-Giemza; A Lewandowska; M Olesińska Journal: Clin Exp Immunol Date: 2021-01-17 Impact factor: 5.732
Authors: John A Reynolds; Tracy A Briggs; Gillian I Rice; Sathya Darmalinggam; Vincent Bondet; Ellen Bruce; Mumtaz Khan; Sahena Haque; Hector Chinoy; Ariane L Herrick; Eoghan M McCarthy; Leo Zeef; Andrew Hayes; Darragh Duffy; Ben Parker; Ian N Bruce Journal: Arthritis Res Ther Date: 2019-06-14 Impact factor: 5.156
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Authors: Sylvie Froidevaux; Marianne M Martinic; Daniel S Strasser; Virginie Sippel; Estelle Gerossier; Ursula Grieder; Gabin M Pierlot; Andrea Kieninger-Graefitsch; Enrico Vezzali; Anna K Stalder; Bérengère Renault; Jesper Ryge; Aaron Hart; Ulrich Mentzel; Peter M A Groenen; Marcel P Keller; Marten Trendelenburg; Mark J Murphy Journal: RMD Open Date: 2020-09
Authors: Marit Stockfelt; Gunilla Larsson; Hanna Engström; Henri Puttonen; Henrik Zetterberg; Kaj Blennow; Christopher Sjöwall; Helena Strevens; Andreas Jönsen; Anders A Bengtsson; Maria Majczuk Sennström; Agneta Zickert; Elisabet Svenungsson; Iva Gunnarsson; Estelle Trysberg; Bo Jacobsson; Anna-Karin Hultgård Ekwall; Karin Christenson; Johan Bylund; Mattias N D Svensson; Anna-Carin Lundell Journal: Lupus Sci Med Date: 2021-03
Authors: Paul Bastard; Lindsey B Rosen; Qian Zhang; Eleftherios Michailidis; Hans-Heinrich Hoffmann; Yu Zhang; Karim Dorgham; Quentin Philippot; Jérémie Rosain; Vivien Béziat; Steven M Holland; Guy Gorochov; Emmanuelle Jouanguy; Charles M Rice; Aurélie Cobat; Luigi D Notarangelo; Laurent Abel; Helen C Su; Jean-Laurent Casanova; Jérémy Manry; Elana Shaw; Liis Haljasmägi; Pärt Peterson; Lazaro Lorenzo; Lucy Bizien; Sophie Trouillet-Assant; Kerry Dobbs; Adriana Almeida de Jesus; Alexandre Belot; Anne Kallaste; Emilie Catherinot; Yacine Tandjaoui-Lambiotte; Jeremie Le Pen; Gaspard Kerner; Benedetta Bigio; Yoann Seeleuthner; Rui Yang; Alexandre Bolze; András N Spaan; Ottavia M Delmonte; Michael S Abers; Alessandro Aiuti; Giorgio Casari; Vito Lampasona; Lorenzo Piemonti; Fabio Ciceri; Kaya Bilguvar; Richard P Lifton; Marc Vasse; David M Smadja; Mélanie Migaud; Jérome Hadjadj; Benjamin Terrier; Darragh Duffy; Lluis Quintana-Murci; Diederik van de Beek; Lucie Roussel; Donald C Vinh; Stuart G Tangye; Filomeen Haerynck; David Dalmau; Javier Martinez-Picado; Petter Brodin; Michel C Nussenzweig; Stéphanie Boisson-Dupuis; Carlos Rodríguez-Gallego; Guillaume Vogt; Trine H Mogensen; Andrew J Oler; Jingwen Gu; Peter D Burbelo; Jeffrey I Cohen; Andrea Biondi; Laura Rachele Bettini; Mariella D'Angio; Paolo Bonfanti; Patrick Rossignol; Julien Mayaux; Frédéric Rieux-Laucat; Eystein S Husebye; Francesca Fusco; Matilde Valeria Ursini; Luisa Imberti; Alessandra Sottini; Simone Paghera; Eugenia Quiros-Roldan; Camillo Rossi; Riccardo Castagnoli; Daniela Montagna; Amelia Licari; Gian Luigi Marseglia; Xavier Duval; Jade Ghosn; John S Tsang; Raphaela Goldbach-Mansky; Kai Kisand; Michail S Lionakis; Anne Puel; Shen-Ying Zhang Journal: Science Date: 2020-09-24 Impact factor: 63.714