Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies

Lorenzo Lodi, Isabelle Melki, Vincent Bondet, Luis Seabra, Gillian I Rice, Edwin Carter, Alice Lepelley, Maria José Martin-Niclós, Buthaina Al Adba, Brigitte Bader-Meunier, Magalie Barth, Thomas Blauwblomme, Christine Bodemer, Odile Boespflug-Tanguy, Russel C Dale, Isabelle Desguerre, Camille Ducrocq, Fabienne Dulieu, Cécile Dumaine, Pierre EllulAlice Hadchouel, Véronique Hentgen, Miguel Hié, Marie Hully, Eric Jeziorski, Romain Lévy, Fanny Mochel, Simona Orcesi, Sandrine Passemard, Marie Pouletty, Pierre Quartier, Florence Renaldo, Rainer Seidl, Jay Shetty, Bénédicte Neven, Stéphane Blanche, Darragh Duffy, Yanick J Crow, Marie-Louise Frémond

Research output: Contribution to journalArticlepeer-review


Whilst upregulation of type I interferon (IFN) signaling is common across the type I interferonopathies (T1Is), central nervous system (CNS) involvement varies between these disorders, the basis of which remains unclear. We collected cerebrospinal fluid (CSF) and serum from patients with Aicardi-Goutières syndrome (AGS), STING-associated vasculopathy with onset in infancy (SAVI), presumed monogenic T1Is (pT1I), childhood systemic lupus erythematosus with neuropsychiatric features (nSLE), non-IFN-related autoinflammation (AI) and non-inflammatory hydrocephalus (as controls). We measured IFN-alpha protein using digital ELISA. Eighty-two and 63 measurements were recorded respectively in CSF and serum of 42 patients and 6 controls. In an intergroup comparison (taking one sample per individual), median CSF IFN-alpha levels were elevated in AGS, SAVI, pT1I, and nSLE compared to AI and controls, with levels highest in AGS compared to all other groups. In AGS, CSF IFN-alpha concentrations were higher than in paired serum samples. In contrast, serum IFN was consistently higher compared to CSF levels in SAVI, pT1I, and nSLE. Whilst IFN-alpha is present in the CSF and serum of all IFN-related diseases studied here, our data suggest the primary sites of IFN production in the monogenic T1I AGS and SAVI are, respectively, the CNS and the periphery. These results inform the diagnosis of, and future therapeutic approaches to, monogenic and multifactorial T1Is.

Original languageEnglish
Pages (from-to)603-609
Number of pages7
JournalJournal of Clinical Immunology
Issue number3
Publication statusPublished - Jan 7 2021


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