Systemic Lupus Erythematosus: Definitions, Contexts, Conflicts, Enigmas.

Area of Science:

• Immunology
• Genetics
• Clinical Medicine

Background:

• Systemic lupus erythematosus (SLE) is a complex autoimmune condition with largely unknown etiology and pathogenesis.
• SLE presents with multiple, etiologically unlinked manifestations, often occurring in stochastic clusters.
• Current classification criteria, such as ACR and SLICC, define SLE based on non-coherent parameters, leading to hundreds of distinct clinical phenotypes.

Purpose of the Study:

• To discuss the challenges in defining Systemic Lupus Erythematosus (SLE) due to its complex and poorly understood nature.
• To highlight the difficulties in identifying reliable biomarkers for SLE, using anti-dsDNA antibodies as a case study.
• To explore how basic scientific evidence is often underutilized in clinical practice for SLE.

Main Methods:

• Literature review and critical analysis of existing classification criteria for SLE.
• Examination of the role and interpretation of anti-dsDNA antibodies in SLE diagnosis and research.
• Discussion of the disconnect between basic science findings and clinical application in SLE management.

Main Results:

• SLE is defined by non-coherent classification criteria, resulting in a highly heterogeneous disease with numerous phenotypes.
• The anti-dsDNA antibody serves as an example of the challenges in finding specific biomarkers for an imperfectly defined syndrome.
• Therapeutic approaches often target dominant symptoms rather than the underlying syndrome, indicating a gap in understanding.

Conclusions:

• The current definition and classification of SLE are problematic, hindering a unified understanding of the disease.
• Rethinking the role of biomarkers like anti-dsDNA antibodies within the context of SLE's complexity is crucial.
• Integrating basic scientific evidence more effectively into clinical practice could advance SLE research and treatment paradigms.