Assessing the role of interferons in congenital and acquired interferonopathies: a review

Abstract

Impaired interferon (IFN) production plays a key role in the pathogenesis of a wide range of autoimmune diseases (AIDs), such as systemic lupus erythematosus (SLE), multiple sclerosis (MS), dermatomyositis, and others. This review examines both the physiological functions of IFNs under normal conditions (antiviral defense, regulation of apoptosis and necroptosis, antitumor immunity) and pathological changes in the IFN system associated with AIDs. Particular attention is paid to the concept of type I interferonopathies. Monogenic forms caused by mutations in genes controlling nucleic acid metabolism and IFN signaling pathways, leading to their hyperproduction, are analyzed. Using SLE and dermatomyositis as examples, the key role of excessive IFN signaling in the development of organ damage is demonstrated. Paradoxically, IFN-β drugs are used in MS therapy due to their immunomodulatory effect. A significant portion of this review is devoted to acquired disorders caused by viral infections. Viruses (herpes, hepatitis, SARS-CoV-2) can induce an autoimmune response through molecular mimicry and interfere with the IFN system at various levels: from blocking recognition receptors to epigenetic silencing of interferon-stimulated genes (ISGs). This creates a vicious cycle in which chronic infection and IFN dysregulation exacerbate the autoimmune process. The conclusion emphasizes the dual nature of IFNs: their deficiency increases susceptibility to infections, while excess or dysfunction provokes autoimmunity. A promising direction is the study of IFN biological activity, the search for markers of treatment efficacy, and the development of methods for correcting IFN status (using exogenous IFNs or their inducers) in the complex treatment of AIDs.