Associated TP23: Identification and the role of autoantibodies against brain epitopes in neuroinflammatory disorders

My PhD project primarily deals with the identification of novel autoantigenic targets in different neuroinflammatory disorders and is divided into multiple shorter studies.

In my first study I qualitatively screened for stroke-specific autoantibodies in serum samples collected at three different time points from a cohort of 76 stroke patients and 25 age-matched controls with no acute neurological disease. Our results demonstrated that stroke is not associated with any generalized increase in autoantibody reactivity to Central Nervous System (CNS) autoantigens. Moreover, the disease associated repertoire was essentially indistinguishable to that in age matched controls and finally, pre-existing autoantibody responses to CNS antigens were identified in most patients.

The second study that I am a part of is an anti-myelin associated glycoprotein (MAG)IgM gammopathy and polyneuropathy where our aims are (I) to establish a sensitive and specific test system that will enable us to detect the presence of this monoclonal anti-MAG IgM antibody in patients with anti-MAG IgM gammopathy and polyneuropathy; (II) to identify any relevant CNS target antigens in a subset of patients with peripheral neuropathy –where preliminary screen revealed a possible reactivity to CNS antigens in addition to antigen-antibody binding on nerve (PNS tissue).

The third study that I am interested in is Multiple Sclerosis (MS). There is increasing evidence that antibody-dependent mechanisms can contribute to the pathogenesis of MS, but their specificity and mode of action remain obscure. This includes data from a large number of studies reporting the presence of expanded clones of antigen experienced B cells that reside in distinct compartments of the CNS and responsible for sustained intrathecal antibody synthesis as well as antibodies detected in the sera of MS patients. It would be of my interest to characterize the cellular and molecular specificity of this disease associated antibody response using tools developed by EUROIMMUN AG, and to possibly explore its functional effects using appropriate in vitro models, where the disease associated antibody repertoire in patients with MS may contribute to disease pathogenesis via a variety of direct or indirect effects.