Thymoma, a rare tumor arising from thymic epithelial cells, leads to autoimmunity in approximately half of the patients. Thymomas often lose their expression of AIRE, resulting in the escape of autoreactive T cells from the thymus mirroring inherited AIRE deficiency that causes the monogenic syndrome, Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). While myasthenia gravis is the most common autoimmune manifestation in thymoma, the patients can share many similarities to APECED patients, including development of autoimmune manifestations such as pneumonitis, endocrinopathies, and production of anti-cytokine antibodies. Recently, we have shown that APECED is characterized by increased IFNγ-driven T-cell–mediated autoimmunity that can be ameliorated with JAK1/2 inhibition.
We stained biopsies from four tissues (lung, liver, stomach, and duodenum) affected by autoimmunity in three patients with thymoma and found increased T cell infiltration and elevated expression of IFNγ-inducible chemokine CXCL9, indicating increased local type-1 immune responses. Moreover, a 45-year-old female thymoma patient who developed increasing autoimmune manifestations despite removal of thymoma >10 years ago was treated with the FDA-approved JAK1/2 inhibitor, baricitinib. The patient had long-standing myasthenia gravis, hypogammaglobulinemia, and immune thrombocytopenia and had developed recent-onset autoimmune lung disease and anemia prior to baricitinib initiation. Baricitinib lead to the clinical improvement of hematological autoimmune diseases and pulmonary symptoms, and at 3 months of treatment pulmonary infiltrates had diminished. At 6 months of treatment, the patient is still on immunoglobulin replacement.
Our results show that autoimmunity in thymoma, which is associated with an acquired AIRE defect, is characterized by increased type-1 immunity, and a blockade of IFNγ downstream signaling with JAK1/2 inhibition can ameliorate autoimmune manifestations.
