Dr. Christopher-Stine shared her hope that other novel antibodies can be identified in the future and that the clinical phenotypes associated with these antibodies can be explored to better inform diagnosis and treatment strategies.
Cancer & Myositis
With regard to cancer, the strongest association is in patients with myositis and antibodies to TIF1γ. Work from Dr. Christopher-Stine and her colleagues has shed light on the processes that may be at play in these patients. Using a proteomic approach, the team identified 10 potentially novel autoantibodies in anti-TIF1γ-positive patients with dermatomyositis, the most common being against cell division cycle and apoptosis regulator protein 1 (CCAR1). Patients whose only antibodies were to TIF1γ had a higher likelihood of developing cancer than patients with antibodies to CCAR1 and other antigens in addition to TIF1γ. Thus, the study hypothesized a model for describing the balance between cancer fitness and immune response.6
In the model’s first scenario, patients with a high fitness cancer and a lack of additional immune responses are most likely to see rapid, aggressive cancer emergence via what is termed immune escape and will only be found to produce antibodies to TIF1γ. In the model’s second scenario, the cancer and immune responses are more balanced—as evidenced by production of a broader range of autoantibodies, including those against CCAR1. The cancer that ultimately develops is less aggressive and delayed in onset from time of dermatomyositis emergence. In the third scenario, a broad and effective immune response capably eliminates the cancer or maintains it in the subclinical state. These patients will have a wide array of autoantibodies and will not show any overt signs of cancer.6
Screening: Although models such as this require further examination, Dr. Christopher-Stine provided clinical pearls gleaned from real-world observations to guide how clinicians should screen for malignancy in patients with idiopathic inflammatory myopathies. In general, the types of cancer most frequently seen in idiopathic inflammatory myopathies are lung, ovarian, colorectal, lymphoma, breast and nasopharyngeal cancer, and typically onset is within one to three years before or after the diagnosis of myositis.
Across all patients with idiopathic inflammatory myopathies, cancer risk appears highest in those with dermatomyositis, antibodies to TIF1γ or NXP-2, age of onset after 40, high disease activity despite immunosuppression, dysphagia, and cutaneous necrosis. Dr. Christopher-Stine cited the International Guideline for Idiopathic Inflammatory Myopathy-Associated Cancer Screening as a particularly helpful resource for rheumatologists.7
