Type I interferon-mediated monogenic autoinflammation: The type I interferonopathies, a conceptual overview

Area of Science:

• Immunology
• Genetics
• Infectious Disease

Background:

• Type I interferon is a potent immune substance.
• Its induction, transmission, and resolution are tightly regulated.
• Type I interferonopathies are defined as Mendelian mutations disrupting this regulation.

Purpose of the Study:

• To define type I interferonopathies.
• To explore the relationship between autoinflammation, autoimmunity, and interferon signaling.
• To highlight the clinical importance of recognizing these disorders.

Main Methods:

• Review of existing literature on type I interferonopathies.
• Analysis of the role of Mendelian mutations in interferonopathies.
• Comparison of interferon signaling in monogenic and non-Mendelian disorders.

Main Results:

• Type I interferonopathies are distinct genetic disorders of immune homeostasis.
• Autoinflammation can be interferon-related or not, with potential to develop into autoimmunity.
• Upregulated type I interferon signaling is observed in non-Mendelian disorders like lupus and dermatomyositis.

Conclusions:

• Further monogenic diseases related to interferonopathies are likely to be identified.
• Recognition of type I interferonopathies is clinically important for targeted therapies.
• Insights from interferonopathies may inform treatment for broader autoimmune and autoinflammatory conditions.