Systemic lupus erythematosus: Is it one disease?

Area of Science:

• Immunology
• Genetics
• Rheumatology

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical manifestations.
• Genetic factors play a role in SLE development, with specific monogenic conditions identified.
• Existing research points to impaired interferon-α regulated gene expression and complement deficiencies as examples.

Purpose of the Study:

• To explore the concept of SLE as a spectrum of diseases rather than a single entity.
• To highlight how specific genetic defects correlate with distinct clinical presentations and disease severity in SLE.
• To advocate for personalized treatment strategies based on identified underlying genetic causes.

Main Methods:

• Review of existing literature on monogenic conditions associated with SLE.
• Analysis of clinical presentations linked to specific genetic defects.
• Correlation of identified genetic defects with disease severity and phenotype.

Main Results:

• Monogenic predisposing conditions, such as impaired interferon-α regulated gene expression and complement deficiencies, are associated with SLE.
• These specific defects manifest with particular clinical presentations and varying degrees of severity.
• The findings support the classification of SLE into distinct subtypes based on underlying genetic etiology.

Conclusions:

• Systemic lupus erythematosus exhibits significant heterogeneity, suggesting it comprises multiple distinct disease subtypes.
• Identifying the specific genetic defect in SLE patients is crucial for understanding disease presentation and severity.
• Individualized treatment strategies tailored to the underlying genetic defect offer a promising approach for managing SLE subtypes.