Purpose of review: Immune deficiency and autoimmunity have been recognized as cotravelers for decades. This clinically oriented review brings together our evolving mechanistic understanding to highlight associations of particular relevance to rheumatologists.
Recent findings: Conceptually, all autoimmunity derives from a loss of tolerance. This distinguishes it from autoinflammation in which the innate immune system is dysregulated without necessarily affecting tolerance. Studies have demonstrated the profound effects of signaling defects, apoptotic pathways and the ramifications of homeostatic proliferation on tolerance. This foundation has translated into an improved understanding of the specific associations of autoimmune diseases with immune deficiencies. This important foundation paves the way for personalized treatment strategies.
Summary: This review identifies critical mechanisms important to conceptualize the association of primary immune deficiencies and autoimmunity. It highlights a growing appreciation of the hidden single gene defects affecting T-cells within the group of patients with early-onset pleomorphic autoimmunity.