Differential levels of IFNα subtypes in autoimmunity and viral infection.

Adolescent Adult Aged Antiviral Agents / immunology Autoimmunity / immunology Child Child, Preschool Female Humans Infant Interferon-alpha / immunology Male Middle Aged Virus Diseases / immunology Young Adult

Anti-IFNα autoantibodies Autoimmunity IFN function IFNα subtypes TLR activation Viral infection

Journal

Cytokine

ISSN: 1096-0023

Titre abrégé: Cytokine

Pays: England

ID NLM: 9005353

Informations de publication

Date de publication:
08 2021

Historique:

received: 03 02 2021

revised: 30 03 2021

accepted: 31 03 2021

pubmed: 5 5 2021

medline: 5 2 2022

entrez: 4 5 2021

Statut: ppublish

Résumé

Type I interferons are essential for host response to viral infections, while dysregulation of their response can result in autoinflammation or autoimmunity. Among IFNα (alpha) responses, 13 subtypes exist that signal through the same receptor, but have been reported to have different effector functions. However, the lack of available tools for discriminating these closely related subtypes, in particular at the protein level, has restricted the study of their differential roles in disease. We developed a digital ELISA with specificity and high sensitivity for the IFNα2 subtype. Application of this assay, in parallel with our previously described pan-IFNα assay, allowed us to study different IFNα protein responses following cellular stimulation and in diverse patient cohorts. We observed different ratios of IFNα protein responses between viral infection and autoimmune patients. This analysis also revealed a small percentage of autoimmune patients with high IFNα2 protein measurements but low pan-IFNα measurements. Correlation with an ISG score and functional activity showed that in this small sub group of patients, IFNα2 protein measurements did not reflect its biological activity. This unusual phenotype was partly explained by the presence of anti-IFNα auto-antibodies in a subset of autoimmune patients. This study reports ultrasensitive assays for the study of IFNα proteins in patient samples and highlights the insights that can be obtained from the use of multiple phenotypic readouts in translational and clinical studies.

Identifiants

DOI: 10.1016/j.cyto.2021.155533 PMID: 33941444 PMC: PMC7614897

pubmed: 33941444

pii: S1043-4666(21)00113-7

doi: 10.1016/j.cyto.2021.155533

pmc: PMC7614897

mid: EMS182765

pii:

doi:

Substances chimiques

Antiviral Agents 0

Interferon-alpha 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

155533

Subventions

Organisme : Wellcome Trust

ID : 208710/Z/17/Z

Pays : United Kingdom

Organisme : Medical Research Council

ID : MR/N00583X/1

Pays : United Kingdom

Informations de copyright

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