Proteasome inhibition with bortezomib depletes plasma cells and autoantibody production in primary thymic cell cultures from early-onset myasthenia gravis patients (P5146)

• DOI: 10.4049/jimmunol.190.supp.68.1
• Publication Date: 2023-01-01T09:51:18Z
• Authors: Alejandro Gomez; Nick Willcox; Kathleen Vrolix; Jonas Hummel; Hans Duimel; Fons Verheyen; Peter Molenaar; Wim Buurman; Pilar Martinez-Ma...; Marc De Baets; Mario Losen
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

Abstract In the autoimmune disease myasthenia gravis (MG), autoantibodies against muscle AChR are mainly produced by both short- and long-lived plasma cells, which resistant to standard immunosuppressive drugs (i.e. glucocorticoids). A novel therapy eliminate cells is proteasome inhibitor bortezomib, used treat patients with multiple myeloma (MM, a cell malignancy). Previously, we demonstrated that bortezomib also reduced autoantibody titers in an animal model of MG (Gomez, A. M. J. Immunol. 2011). The thymus frequently enriched germinal centers contains produce vitro, even after irradiation (which depletes B T lymphocytes). We studied vitro effects cultured from undergoing therapeutic thymectomy. Treatment single dose blocked production these pathogenic autoantibodies, total IgG levels eliminated cells. Ultrastructural signs apoptosis were detected as early 8 h addition bortezomib; at 24 h, no could be detected. Moreover, minimum concentration eliminates 60-fold lower than peak found MM treated suggesting low doses might effective for eliminating antibody-mediated diseases.