Pilar Martinez & Mario Losen
Autoimmune factors in Psychosis, Schizophrenia and Depression (ZonMW, Hersenstichting, NWO subsidienummer Aspasia: 015.011.033). We aim to develop new methods to diagnose psychosis with autoimmune origin in order to enable specific immunosuppressive treatment of patients. These methods include a cell-based assay where human kidney cells are expressing the relevant target proteins and brain slices where binding of autoantibodies to intact neurons and non-nervous cells is analyzed.
Myasthenia gravis and related Neuromuscular Diseases (MG project: Association française contre les Myopathies, AFM-20851). In MG we are investigating the possible use of proteasome inhibitors for targeting autoimmune long-living plasma cells. These plasma cells are resistant against broad-range immunosuppressants and since they keep producing autoantibodies this is a major problem in the current treatment of MG and other antibody-mediated autoimmune diseases. Plasma cells depend on their proteasome to sustain high-rate protein synthesis. Consequently, proteasome inhibitors have the capacity to kill plasma cell by inducing accumulation of the terminal unfolded proteins that ultimately are lethal for these cells. In a variant of MG caused by antibodies against the synaptic protein MuSK we aim to provide a human recombinant monoclonal MuSK autoantibody. This enables us to study the pathogenic mechanisms. Here we also aim to find the cellular B cell subset responsible for the production of MuSK autoantibodies which may identify therapeutic targets for a tailored therapy.
School for Mental Health and Neurosciences, Maastricht University, Maastricht, The Netherlands
Saxena A, Stevens J, Cetin H, Koneczny I, Webster R, Lazaridis K, Tzartos S, Vrolix K, Nogales-Gadea G, Machiels B, Molenaar PC, Damoiseaux J, De Baets MH, Simon-Keller K, Marx A, Vincent A, Losen M, Martinez-Martinez P. Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient. Sci Rep. 2017
Koneczny I, Stevens JA, De Rosa A, Huda S, Huijbers MG, Saxena A, Maestri M, Lazaridis K, Zisimopoulou P, Tzartos S, Verschuuren J, van der Maarel SM, van Damme P, De Baets MH, Molenaar PC, Vincent A, Ricciardi R, Martinez-Martinez P, Losen M. IgG4 autoantibodies against muscle-specific kinase undergo Fab-arm exchange in myasthenia gravis patients. J Autoimmun. 2017
de Witte LD, Hoffmann C, van Mierlo HC, Titulaer MJ, Kahn RS, Martinez-Martinez P; European Consortium of Autoimmune Mental Disorders (CAIMED). Absence of N-Methyl-D-Aspartate Receptor IgG Autoantibodies in Schizophrenia: The Importance of Cross-Validation Studies. JAMA Psychiatry. 2015
Vrolix K, Fraussen J, Losen M, Stevens J, Lazaridis K, Molenaar PC, Somers V, Bracho MA, Le Panse R, Stinissen P, Berrih-Aknin S, Maessen JG, Van Garsse L, Buurman WA, Tzartos SJ, De Baets MH, Martinez-Martinez P. Clonal heterogeneity of thymic B cells from early-onset myasthenia gravis patients with antibodies against the acetylcholine receptor. J Autoimmun. 2014
van der Neut Kolfschoten M, Schuurman J, Losen M, Bleeker WK, Martínez-Martínez P, Vermeulen E, den Bleker TH, Wiegman L, Vink T, Aarden LA, De Baets MH, van de Winkel JG, Aalberse RC, Parren PW. Anti-inflammatory activity of human IgG4 antibodies by dynamic Fab arm exchange. Science. 2007