The group initially dealt with the role of B lymphocytes in the context of vasculitides. Here, tissue-resistant B-lymphocytes were microdissected and the V-genes of the B-cell receptors (BCR) were amplified, expressed and screened for their target antigens. In the course of these studies, progranulin (PGRN), an endogenous antagonist of TNF-alpha and TL1a, was identified as a frequent target of autoantibodies in the entire spectrum of vasculitides. Subsequent studies also showed the presence of PGRN-antibodies in other autoimmune diseases. The autoantibodies have a neutralizing and therefore pro-inflammatory effect. In addition, a second PGRN isoform (Ser81 PGRN) was identified specifically in patients with PGRN-antibodies. Ser81 PGRN is immunogenic and has lost its ability to interact with TNFR1, 2 and DR3. Thus, a dual proinflammatory mechanism could be demonstrated for PGRN. Due to the pathogenically partial close relationship between autoreactive and lymphoproliferative diseases, BCR expression cloning of different B-cell lymphomas (PCNSL, DLBCL, MCL, NLPHL) was carried out in further projects since precisely for these lymphoma entities indications of a chronic B cell receptor stimulation exist. These projects were carried out in close cooperation with the group of Sylvia Hartmann from the Dr. Senckenberg Institute of Pathology in Frankfurt a.M.. For each of the above-mentioned lymphoma entities, a pathogenically relevant target antigen could be identified, i.e. a lymphoma BCR target antigen that occurs in a variety of different patients with the same lymphoma. We are currently working on the further characterization of the identified target antigens, as well as reasons for the selective immunogenicity of a certain antigen in a specific lymphoma entity.
Furthermore, we are looking with improved techniques for further new targets and have extended our search to other B cell neoplasms as well. We hope that the identified target antigens will be used therapeutically (as immunotoxins, or as bait for CAR-T / NK cells or bispecific antibodies) and diagnostically in future.
Further research focuses on proteomic studies on new specific target antigens of neoplasia and the proteomic investigation of immune checkpoints.