The intersection of immune deficiency and autoimmunity

Area of Science:

• Immunology
• Rheumatology
• Genetics

Background:

• Immune deficiency and autoimmunity have long been recognized as co-occurring conditions.
• A mechanistic understanding is crucial for clinical relevance, especially for rheumatologists.

Purpose of the Study:

• To review the evolving mechanistic understanding of the association between immune deficiency and autoimmunity.
• To highlight associations particularly relevant to rheumatologists.

Main Methods:

• This is a review article, synthesizing existing research and mechanistic insights.
• Focuses on conceptual understanding and clinical relevance.

Main Results:

• Autoimmunity arises from a loss of immune tolerance, distinct from autoinflammation.
• Signaling defects, apoptotic pathways, and homeostatic proliferation significantly impact tolerance.
• Improved understanding of autoimmune disease associations with immune deficiencies is emerging.

Conclusions:

• Critical mechanisms linking primary immune deficiencies and autoimmunity are identified.
• There is a growing recognition of single gene defects impacting T-cells in early-onset autoimmunity.