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Journal Articles Journal of Clinical Immunology Year : 2021

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

1 Equipe Inserm U1163 - Laboratory of neurogenetics and neuroinflammation
2 Azienda Ospedaliero Universitaria A. Meyer [Firenze, Italy]
3 AP-HP Hôpital universitaire Robert-Debré [Paris]
4 Service d'immuno-hématologie pédiatrique [CHU Necker]
5 Immunologie Translationnelle - Translational Immunology lab
6 University of Manchester [Manchester]
7 University of Edinburgh
8 Sidra Medicine [Doha, Qatar]
9 MITOVASC - MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale
10 Service de neurochirurgie pédiatrique [CHU Necker]
11 Service de dermatologie [CHU Necker]
12 The University of Sydney
13 Service de neurologie pédiatrique [CHU Necker]
14 CHU-Lenval - Hôpitaux Pédiatriques de Nice Lenval
15 Child and Adolescent Psychiatry Department [AP- HP Hôpital Robert Debré]
16 I3 - Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière]
17 Service de Pneumologie Allergologie [CHU Necker]
18 CHV - Centre Hospitalier de Versailles André Mignot
19 Centre National de Référence du Lupus Systémique, Syndrome des Anticorps Anti-phospholipides et Maladies Auto-immunes Systémiques Rares [CHU Pitié Salpêtrière]
20 Département Pédiatrie [CHRU Montpellier]
21 UF Neurométabolique Bioclinique et Génétique [CHU Pitié-Salpêtrière]
22 ICM - Institut du Cerveau = Paris Brain Institute
23 Fondazione "Istituto Neurologico Nazionale C. Mondino"
24 UNIPV - Università degli Studi di Pavia = University of Pavia
25 CHU Trousseau [APHP]
26 Medizinische Universität Wien = Medical University of Vienna
27 Royal Hospital for Sick Children [Edinburgh]


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.

Dates and versions

pasteur-03236262 , version 1 (26-05-2021)



Lorenzo Lodi, Isabelle Melki, Vincent Bondet, Luis Seabra, Gillian I. Rice, et al.. Differential Expression of Interferon-Alpha Protein Provides Clues to Tissue Specificity Across Type I Interferonopathies. Journal of Clinical Immunology, 2021, 41 (3), pp.603-609. ⟨10.1007/s10875-020-00952-x⟩. ⟨pasteur-03236262⟩
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