The link between rheumatic disorders and inborn errors of immunity

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Inborn errors of immunity (IEIs) are genetic disorders affecting immune system function.
• While often presenting with infections, IEIs increasingly manifest with non-infectious symptoms like autoimmunity and autoinflammation.
• Recent discoveries link specific IEIs to rheumatic diseases, highlighting immune dysregulation as a key feature.

Purpose of the Study:

• To review novel IEIs that primarily cause autoimmunity or autoinflammation.
• To elucidate the pathogenic mechanisms underlying these IEIs.
• To explore the pathophysiological and clinical relevance of IEIs in systemic rheumatic disorders.

Main Methods:

• Literature review of recent studies on IEIs.
• Analysis of genetic variants and their associated immune dysregulation.
• Correlation of IEI mechanisms with systemic rheumatic disease pathogenesis.

Main Results:

• Identification of newly reported IEIs characterized by autoimmune/autoinflammatory phenotypes.
• Elucidation of specific genetic defects leading to immune dysregulation.
• Demonstration of shared pathomechanisms between IEIs and systemic rheumatic disorders.

Conclusions:

• IEIs are a significant cause of autoimmunity and autoinflammation, including rheumatic conditions.
• Studying IEIs provides crucial insights into the pathogenesis of systemic rheumatic diseases.
• Further research into IEIs can inform diagnosis and treatment strategies for immune-related disorders.