Ro52/TRIM21 - From host defense to autoimmunity

Ro52 (TRIM21) belongs to the ubiquitin ligase family. This protein plays a crucial role in many immunological processes, including antibody-dependent intracellular neutralization, synergy with the complement system, antiviral response, death mediation, oxidative stress response, and protein ubiquitination. Abnormal expression of TRIM21 can break immunological tolerance and lead to the production of autoantibodies against TRIM21. Antibodies against TRIM21 are detected in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), or myositis. However, anti-TRIM21 presence is not limited to autoimmune connective tissue disorders. It was observed in patients with malignancies, various cancerous processes, infectious diseases, and idiopathic interstitial pneumonia. The occurrence of TRIM21 autoantibodies is also associated with clinical features, such as the prevalence of interstitial lung diseases and cardiac or haematological involvement in connective tissue disorders. The purpose of this review was to summarize current knowledge of the immunological functions of TRIM21 and analyze the clinical implications of anti-TRIM21 antibodies in the disease course.