Reply to Hasenkrug et al., “Different Biological Activities of Specific Interferon Alpha Subtypes”

Schlaepfer, Erika; Fahrny, Audrey; Gruenbach, Maarja; Kuster, Stefan P.; Simon, Viviana; Schreiber, Gideon; Speck, Roberto F.

doi:10.1128/msphere.00275-19

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…Some IFNα subtypes were better at inducing certain immune responses in vivo [13,18] and may trigger distinct intracellular signaling pathways [19]. Nevertheless, the notion of qualitative differences between IFNα subtypes remains controversial [20,21]. One reason is that most comparative studies normalized IFN-Is using protein amounts or Units/ml based on inhibition of vesicular stomatitis virus or encephalomyocarditis virus [1].…”

Section: Introductionmentioning

confidence: 99%

Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis

Guo

Shen²,

Kibbie

et al. 2020

PLoS Pathog

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Section: Introductionmentioning

confidence: 99%

Qualitative Differences Between the IFNα subtypes and IFNβ Influence Chronic Mucosal HIV-1 Pathogenesis

Guo

Shen²,

Kibbie

et al. 2020

PLoS Pathog

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“…Furthermore, within the IFNα types there are 13 subtypes that exhibit marked evolutionary differences in terms of selective conservation, suggesting different immunological relevance 5 . Some studies have reported differential functions, at least in terms of anti-viral responses 6,7,8,9 , but much remains unknown in terms of broader differential activity between the different IFNα subtypes. Furthermore, in autoimmunity, the potential role of different IFNα subtypes is even less clear, despite their strong implication in the pathogenesis of many such diseases 10 .…”

Section: Introductionmentioning

confidence: 99%

Differential levels of IFNα subtypes in autoimmunity and viral infection

Bondet

Rodero

Posseme

et al. 2021

Preprint

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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.

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