**Background of TTN Antibodies**
Titin (TTN) antibodies target titin, a giant sarcomeric protein encoded by the *TTN* gene, which is critical for muscle elasticity, contraction, and structural integrity in cardiac and skeletal muscles. As the largest human protein, titin plays key roles in maintaining sarcomere organization and mechanosensory signaling. TTN antibodies are primarily studied in the context of autoimmune disorders, particularly myasthenia gravis (MG) and thymoma-associated autoimmunity.
First identified in the 1990s, TTN antibodies are detected in ~20-30% of MG patients, often those with thymoma or late-onset MG. Their presence is associated with severe clinical phenotypes, including respiratory involvement and poor treatment response. While the exact pathogenic role remains unclear, these antibodies may arise due to thymic dysfunction, where aberrant immune responses target titin epitopes exposed during thymoma-related inflammation or necrosis.
TTN antibodies are also explored in cardiomyopathies and inflammatory myopathies, though their clinical utility here is less defined. Detection methods include ELISA and cell-based assays, but standardization challenges persist. Recent studies highlight their potential as biomarkers for disease stratification or prognosis in autoimmune and cardiac conditions. However, cross-reactivity with other proteins and variable prevalence across populations necessitate further research to clarify their diagnostic and therapeutic relevance.