Differential levels of IFNα subtypes in autoimmunity and viral infection

Bondet, Vincent; Rodero, Mathieu P; Posseme, Céline; Bost, Pierre; Decalf, Jérémie; Haljasmägi, Liis; Bekaddour, Nassima; Rice, Gillian I.; Upasani, Vinit; Herbeuval, Jean-Philippe; Reynolds, John A.; Briggs, Tracy A; Bruce, Ian N.; Mauri, Claudia; Isenberg, David; Menon, Madhvi; Hunt, David; Schwikowski, Benno; Mariette, Xavier; Pol, Stanislas; Rozenberg, Flore; Cantaert, Tineke; Gottenberg, Jacques Éric; Kisand, Kai; Duffy, Darragh

doi:10.1016/j.cyto.2021.155533

Cited by 15 publications

(18 citation statements)

References 29 publications

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“…IFN proteins have been challenging to directly quantify due to their low physiological concentrations in biological samples, and most studies have utilized proxy readouts such as interferon stimulated gene (ISG) expression or cytopathic assays. The development of digital ELISA such as Simoa overcame these challenges as we demonstrated by the measurement of all 13 IFNα human subtypes, and more recently specifically IFNα2 in multiple human cohorts ( 31 , 32 , 41 ). However, additional challenges exist for the study of interferon in non-human species, in particular bats, most notably the lack of specific reagents, in particular monoclonal antibodies which are required for ELISA technologies.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma was then removed and stored at -80°C until Simoa analysis. Human plasma samples measured for IFNα2 from previously published studies were included for comparison including healthy controls ( 31 ), patients with systemic lupus erythematosus (SLE) and acute dengue viral infection ( 32 ).…”

Section: Methodsmentioning

confidence: 99%

“…All plasma samples were first thawed and centrifuged at 10.000g, +4°C for 10 minutes to remove debris. Because bats can harbor many viruses, supernatants were treated in a P2 laboratory for viral inactivation using a standard solvent/detergent protocol used for human blood plasma products ( 34 , 35 ) and described in ( 36 ) and in ( 32 ). Briefly, samples were treated with Tri- n -Butyl Phosphate (T n BP) 0.3% (v/v) and Triton X100 (TX100) 1% (v/v) for 2 hours at room temperature.…”

Section: Methodsmentioning

confidence: 99%

“…The Simoa hIFNα2 assay was developed using the Quanterix Homebrew kit and described in ( 32 ). The BMS216C (eBioscience) antibody clone was used as a capture antibody after coating on paramagnetic beads (0.3mg/mL), and the BMS216BK biotinylated antibody clone was used as the detector at a concentration of 0.3ug/mL.…”

Section: Methodsmentioning

confidence: 99%

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Constitutive IFNα Protein Production in Bats

et al. 2021

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Bats are the only mammals with self-powered flight and account for 20% of all extant mammalian diversity. In addition, they harbor many emerging and reemerging viruses, including multiple coronaviruses, several of which are highly pathogenic in other mammals, but cause no disease in bats. How this symbiotic relationship between bats and viruses exists is not yet fully understood. Existing evidence supports a specific role for the innate immune system, in particular type I interferon (IFN) responses, a major component of antiviral immunity. Previous studies in bats have shown that components of the IFN pathway are constitutively activated at the transcriptional level. In this study, we tested the hypothesis that the type I IFN response in bats is also constitutively activated at the protein level. For this, we utilized highly sensitive Single Molecule (Simoa) digital ELISA assays, previously developed for humans that we adapted to bat samples. We prospectively sampled four non-native chiroptera species from French zoos. We identified a constitutive expression of IFNα protein in the circulation of healthy bats, and concentrations that are physiologically active in humans. Expression levels differed according to the species examined, but were not associated with age, sex, or health status suggesting constitutive IFNα protein expression independent of disease. These results confirm a unique IFN response in bat species that may explain their ability to coexist with multiple viruses in the absence of pathology. These results may help to manage potential zoonotic viral reservoirs and potentially identify new anti-viral strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Constitutive IFNα Protein Production in Bats

et al. 2021

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“…Следует подчеркнуть, что методы определения IFNGS недостаточно стандартизованы, а результаты зависят от композиции исследуемых клеток (цельная кровь, отдельные клеточные популяции) и числа исследуемых генов ИФН типа I. Кроме того, отмечается значительный перекрест экспрессии генов, индуцируемых ИФН типа I, II и III. Все это вместе взятое затрудняет интерпретацию результатов определения IFNGS в клинической практике, хотя и установлено, что при СКВ выявляются более сложные «паттерны» экспрессии генов ИФН типа I, чем при вирусных инфекциях [16]. Не удивительно, что данные, касающиеся взаимосвязи между выраженностью экспрессии IFNGS и клиническими характеристиками СКВ, противоречивы.…”

Section: New Possibilities Of Pharmacotherapy For Systemic Lupus Erythematosus: Prospects For the Use Of Anifrolumab (Monoclonal Antibodiunclassified

New possibilities of pharmacotherapy for systemic lupus erythematosus: Prospects for the use of anifrolumab (monoclonal antibodies to type I interferon receptor)

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Авдеева²,

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2021

Naučno-praktičeskaâ revmatologiâ

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Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by overproduction of organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. According to modern concepts, one of the key mechanisms of SLE immunopathogenesis is associated with dysregulation of type I interferon (IFN) synthesis The complex of data obtained in the process of fundamental and clinical research served as the basis for the development of a new approach to the pharmacotherapy of SLE, associated with the use of monoclonal antibodies (mAbs) that block the activity of IFN type I or its receptors. Among these drugs, anifrolumab (AFM) occupies a special place, which is a human IgG1 mAbs that bind to cellular receptors for IFN-α. The article discusses the materials of the main studies concerning the efficacy and safety of AFM in SLE, and the prospects for the use of this drug in the treatment of this disease.

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Heterogeneity and functions of the 13 IFN‐α subtypes – lucky for some?

et al. 2023

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Type I IFNs are critical for host responses to viral infection and are also implicated in the pathogenesis of multiple autoimmune diseases. Multiple subtypes exist within the type I IFN family, in particular 13 distinct IFN‐α genes, which signal through the same heterodimer receptor that is ubiquitously expressed by mammalian cells. Both evolutionary genetic studies and functional antiviral assays strongly suggest differential functions and activity between the 13 IFN‐α subtypes, yet we still lack a clear understanding of these different roles. This review summarizes the evidence from studies describing differential functions of IFN‐α subtypes and highlights potential reasons for discrepancies between the reports. We examine both acute and chronic viral infection, as well as autoimmunity, and integrate a more recent awareness of the importance of anti‐IFN‐α autoantibodies in shaping the type I IFN responses in these different conditions.

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Differential levels of IFNα subtypes in autoimmunity and viral infection

Cited by 15 publications

References 29 publications

Constitutive IFNα Protein Production in Bats

Constitutive IFNα Protein Production in Bats

New possibilities of pharmacotherapy for systemic lupus erythematosus: Prospects for the use of anifrolumab (monoclonal antibodies to type I interferon receptor)

Heterogeneity and functions of the 13 IFN‐α subtypes – lucky for some?

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