Cell-based assays to detect cytokine autoantibodies in patients with myasthenia gravis
Chang P-S., WATERS P., LEITE M.
Myasthenia gravis (MG) is an autoimmune disease that presents with fatigable muscle weakness caused by the autoantibodies mostly to acetylcholine receptor (AChR). Around 10-15% of MG patients have thymoma, which contributes to the dysregulation of negative selection and permits the production of autoantibodies to soluble cytokines, e.g., type I interferons, IL-12/IL-23 etc. Those autoantibodies can neutralize their targets and disrupt their normal functions in patients. To detect them, HEK293T cells were transfected with the DNA constructs for expressing the targeted cytokines above cell membrane. This was to provide the native substrates for antibody binding and to detect cytokine autoantibodies more sensitively. Moreover, myc tag was incorporated for our benefit to quantify the surface expression of targeted cytokines. Our platform was able to prognose the presence of thymoma in a series of thymoma-related autoimmune disorders, e.g. thymoma-associated MG (TAMG), late-onset MG (LOMG), neuromyotonia (NMT) and Good’s syndrome. In general, we have established a live cell-based assay to optimize the detection of cytokine autoantibodies in the sera from patients with thymoma for gaining proof of concept and beneficial clinical interpretations. The poster was presented at International Thymic Malignancy Interest Group (ITMIG) 2019 Annual Conference.