Anti-Ku Antibodies

SARDs are a heterogeneous group of disorders characterized by dysregulation of the immune system, that starts to turn against the body’s own tissues. Major SARDs include systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis and Sjögren’s syndrome. These diseases can affect multiple organs and share common symptoms such as fatigue, fever, joint pain and skin rash. Diagnosis relies on a combination of clinical assessment and specific autoantibody tests. Early diagnosis is crucial to initiate appropriate therapy and slow down disease progression.

Anti-Ku autoantibodies are directed against the nuclear Ku heterodimer, that is made up of two subunits of 70 and 80 kDa respectively, involved in double-strand DNA repair and transcription regulation. Initially associated with patients presenting myositis/scleroderma overlap, they have since been detected across a broad spectrum of connective tissue diseases (SARD), including overlap syndromes with systemic lupus erythematosus (SLE), systemic sclerosis and mixed or undifferentiated connective tissue disease.

Anti-Ku–positive patients more frequently present with arthralgia, Raynaud’s phenomenon, musculoskeletal manifestations (myositis and muscle weakness) and interstitial lung disease (ILD), the latter being considered one of the most clinically significant complications.

In patients with anti-Ku–positive myositis, ILD generally shows a severe course and poor response to steroid therapy, whereas muscular and articular manifestations respond more favourably to corticosteroids.