Proteasome disorders and inborn errors of immunity

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• Inborn errors of immunity (IEI), or primary immune deficiencies (PIDD), stem from genetic variants affecting immune response molecules.
• Over 450 genes are implicated in IEI, leading to diverse symptoms like infections, autoimmunity, and autoinflammation.
• Autoinflammatory IEI are classified by the affected inflammatory pathway, including interferonopathies characterized by type I interferon gene upregulation.

Purpose of the Study:

• To review the clinical, genetic, and molecular characteristics of IEI associated with proteasome gene mutations.
• To explore how studying proteasome-related IEI informs therapeutic interventions.
• To highlight the growing area of research into proteasome defects in autoinflammatory diseases.

Main Methods:

• Literature review of genetic defects affecting the proteasome in the context of autoinflammatory diseases.
• Analysis of clinical manifestations, genetic underpinnings, and molecular mechanisms of these IEI.
• Synthesis of current knowledge on therapeutic strategies derived from these studies.

Main Results:

• Genetic defects impacting the proteasome are a recognized cause of autoinflammatory disease within the interferonopathy spectrum.
• These mutations lead to distinct clinical presentations and molecular dysregulation.
• Understanding these proteasome-related IEI has paved the way for targeted therapeutic approaches.

Conclusions:

• Proteasome gene mutations represent a significant cause of autoinflammatory interferonopathies.
• Research into these IEI provides crucial insights into immune system regulation and potential treatments.
• Further investigation into proteasome function in immunity is essential for advancing therapeutic options.