Systemic auto-inflammatory diseases, auto-immune diseases and immune deficiencies: From independent to overlapped diseases approach

Abstract

Systemic AutoInflammatory Diseases (SAIDs), AutoImmune Diseases (AIDs), and Primary Immune Deficiencies (PIDs) were formely considered independent, even opposing, conditions. SAIDs were associated with the innate immune system, involving dysregulation of inflammation and recurrent episodes of systemic inflammation without an infectious process. Their original definition did not involve autoreactive cells or autoantibodies. In contrast, PIDs were characterised by defects in the adaptive or innate immune system, leading to recurrent infections and immune dysfunction. AIDs were inflammatory diseases also characterised by dysregulation of the immune system attacking its own tissues through autoreactive cells or autoantibodies. Nevertheless, advancements in genetics and a deeper understanding of T-cell development and signalling, immune tolerance, the complement pathway and inflammation have revealed that these conditions are overlapping diseases with shared immune system dysfunctions. These diseases now represent a continuum within a broader spectrum of disorders known as “Inborn Errors of Immunity”. However, this term is not suitable as it does not fully encompass cases arising from somatic mutations and can be stigmatising for patients. Therefore, we propose the terms “Primary Immune Deficiencies and Dysregulations” (PIDDs) or simply “Primary Immune Disorders” (PIDs) as more appropriate alternatives.

Thus, this article aims to describe known diseases where autoimmunity, autoinflammation and primary immunodeficiencies overlap, along with some mechanisms that may explain these interconnections. To our knowledge, no comprehensive reviews on this topic currently exist, despite its significance in modifying our understanding of these diseases, their treatment, and associated research.