" TREX1 Gene Mutations and Their Role in Systemic Lupus Erythematosus

Cutaneous lesions are among the earliest and most frequent features of SLE, with over 70% of patients developing mucocutaneous involvement during their disease course.

The presence and severity of cutaneous manifestations have been associated with specific autoantibodies, such as anti-Ro/SSA and anti-dsDNA, which may reflect underlying genetic susceptibility.

Recent studies have also implicated gene polymorphisms in IRF5, STAT4, TREX1, and TNFA in the pathogenesis of cutaneous SLE phenotypes.

Defective TREX1 exonuclease activity, leading to intracellular accumulation of DNA, may trigger type I interferon activation-a key mechanism in lupus pathophysiology.

Despite the extensive global literature, data from Egyptian patients remain limited, especially regarding the relationship between TREX1 gene variants and cutaneous lupus phenotypes.

Understanding how autoantibody profiles and gene polymorphisms relate to clinical features and disease activity could enhance early diagnosis, predict flares, and improve personalized therapy.

Inclusion criteria

• Adult aged 18-60 years
• Diagnosed as SLE per 2019 EULAR/ACR classification criteria.
• Presence of at least one cutaneous manifestation (acute, subacute, or chronic).
• Willing to provide written informed consent for participation and genetic testing

Exclusion criteria

• Overlap autoimmune syndromes (e.g., dermatomyositis, systemic sclerosis).
• Systemic infection, malignancy, or pregnancy.
• Use of biologic therapy or immunosuppressive pulses within one month.