Type 1 interferonopathies

Author:Prof. Dr. med. Peter Altmeyer

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Last updated on: 11.12.2023

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Synonym(s)

Interferonopathies, Type I; Type 1 interferonopathies; Type I interferonopathies

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HistoryThis section has been translated automatically.

Crow Y, 2011

DefinitionThis section has been translated automatically.

The type 1 interferonopathies represent a group of rare, genetically and phenotypically heterogeneous diseases caused by a malfunction of the innate immune system (Crow YJ 2011). With the exception of multifactorial SLE, these are very rare disorders.

Note: By elucidating the genetic causes of rare monogenic disease patterns associated with chronic type 1 interferon activation, new disease mechanisms have been identified that can be linked to autoinflammation and autoimmunity.

Thus, the central role of type I interferons in the pathogenesis of autoimmune diseases first became apparent in systemic lupus erythematosus (SLE) (Vallin H et al. 1999). SLE patients exhibit a strong Toll-like receptor-mediated interferon signature (upregulation of interferon-stimulated genes) in the blood (Baechler EC et al. 2003).

Major type I interferon producers are plasmacytoid dendritic cells, which are particularly activated in patients with SLE (Vallin H et al. 1999; Lande R et al. 2007).

ClassificationThis section has been translated automatically.

The monogenic and polygenic clinical pictures listed below are summarized under the term type 1 interferonopathies (see also Immunodeficiencies/autoiflammatory diseases/CrowY, 2011):

EtiopathogenesisThis section has been translated automatically.

Pathogenetically, type 1 interferonopathies are based on disturbances in metabolism and in the immunological recognition of intracellular nucleic acids. The dysregulation of the type-1 interferon (IFN) axis leads to a constitutive type-1 interferon activation which can lead to the following molecular consequences:

  • disturbed negative regulation of type 1 IFN signalling pathways.
  • increased or altered sensitivity of nucleic acid sensors
  • Ligand independent activation of components of downstream signal cascades
  • unphysiological accumulation or chemical modification of endogenous nucleic acids

PathophysiologyThis section has been translated automatically.

Type 1 interferons(IFN-α and IFN-β) act as essential effector cytokines of the immune response to pathogenic germs. The production of type 1 interferons (type 1 IFN) is induced by receptors of the innate immune system that detect pathogenic danger signals. Activation of the type 1 IFN signaling cascade results in the transcriptional induction of hundreds of IFN-stimulated genes, the interaction of which places the host organism in an antiviral state with the aim of eliminating infected cells and limiting the spread of infection. Uncontrolled activation of type 1 IFN can have negative consequences for the host organism, as it promotes inadequate inflammatory processes and the loss of immunological tolerance.

TherapyThis section has been translated automatically.

Our current understanding of the molecular pathogenesis of type 1 interferonopathies suggests that an immunomodulatory intervention that counteracts inadequate type 1 IFN activation could be therapeutically effective (see below for the individual clinical pictures)

LiteratureThis section has been translated automatically.

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Last updated on: 11.12.2023