The mosaic of systemic lupus erythematosus: From autoimmunity to autoinflammation and immunodeficiency and back

The concept of an “immunological continuum model,” introduced by McGonagle and McDermott in 2006, redefines the traditional dichotomy between autoimmunity and autoinflammation, proposing a spectrum where innate and adaptive immune dysregulation can co-occur, reflecting a more nuanced understanding of immune disorders.

Systemic lupus erythematosus (SLE) exemplifies the complexity of this continuum, often displaying manifestations of autoimmunity, autoinflammation, and immunodeficiency. The interplay between genetic, epigenetic, hormonal, psychological, and environmental factors contributes to its distinctive immunopathological signatures. Historically recognized as a systemic disease with diverse clinical manifestations, SLE is primarily a polygenic autoimmune condition but can, however, present in monogenic forms.

Examining SLE through the lens of the immunological continuum model allows for emphasis on the contributions of both innate and adaptive immunity. SLE and primary immunodeficiencies share genetic susceptibilities and clinical manifestations. Additionally, autoinflammatory mechanisms, such as inflammasome activation and interferonopathies, can play a role in SLE pathogenesis, illustrating the disease's position at the crossroads of immune dysregulation.

Recognizing the diverse clinical expressions of SLE and its mimickers is critical for accurate diagnosis and targeted therapy.

In conclusion, the immunological continuum model provides a comprehensive framework for understanding SLE, acknowledging its multifaceted nature and guiding future research and clinical practice toward more effective and individualized treatments. After the Mosaic of Autoimmunity, it is now the time to focus and attempt to solve the intricate mosaic of SLE.