Laboratory of Translational Immunology
The current focus of Prof. Seebach’s laboratory is to better characterize the factors that shape antibody-dependent innate immune cell responses and to predict the effects of monoclonal antibody (mAb) therapies in the context of autoimmunity. His research explores the cellular crosstalk and interactions between innate immune cells during the clearance of antibody-coated target cells. This work involves both conventional static assays and a novel 3D micro-vessel system with a pulsatile flow that mimics intravascular conditions, following the 3R principle. The ultimate goal is to achieve a deeper understanding of the pathophysiology of innate immune responses triggered by IgG–FcγR interactions in antibody-associated autoimmune pathologies and after therapeutic mAb applications, including ADCC and ADPC. This approach may allow better prediction of therapeutic mAb efficiency in individual patients. Additionally, elucidating the molecular mechanisms of crosstalk among innate immune cells could lead to the development of novel therapeutic hypotheses and strategies.
SPECIFIC EXPERTISE
Prof. Seebach’s expertise lies in Translation and Clinical Immunology. As a clinician, he has been continually shaped by clinical practice and, driven by his curiosity, has contributed to multiple areas of clinical immunology throughout his career. These include evaluating the predictive value of simple neutrophil left shift for inflammatory and infectious diseases; identifying risk factors in intensive care patients after hematopoietic stem cell transplantation; diagnosing and treating rare autoinflammatory and autoimmune pathologies; assessing immune deficiencies in patients; and participating in both retrospective and prospective clinical studies.
Earlier in his career, Prof. Seebach focused on interactions between human NK cells and porcine endothelial cells (pEC) in the field of xenotransplantation. Together with collaborators, he contributed to key insights on NK cell activation, inhibition, and function during xenorejection. His work demonstrated that ADCC against pEC mediated by human NK cells in the presence of xenoreactive antibodies is not affected by blocking activating NK receptors. Direct NK cytotoxicity of pEC depended predominantly on the perforin/Granzyme B pathway and was triggered by the activating receptors NKp44 and NKG2D, but not by NKp30 or NKp46. He later explored the potential of regulatory cells, including Treg subpopulations and tolerogenic dendritic cells, to prevent transplant rejection.
In recent years, Prof. Seebach has demonstrated the effects of immunosuppressive drugs and therapeutic immunoglobulins on NK cytotoxicity, including ADCC. His laboratory has gained extensive experience in functional assays for ADCC, ADCP, and cytokine production by innate immune cells following FcR engagement, revealing the differential effects of IgG subclasses.
SELECTED PUBLICATIONS
Seebach JD, Morant R, Rüegg R, Seifert B, Fehr J. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am. J. Clin. Pathol. 1997; 107:582-591
Weiss E*, Lilienfeld B*, Müller S, Müller E, Herbach N, Kessler B, Wanke R, Schwinzer R, Seebach JD*, Wolf E*, Brem G*. HLA-E/human 2-microblobulin transgenic pigs: protection agains xenogeneic human anti-pig natural killer cell cytotoxicity. Transplantation 2009;87;1:3543
Muller YD, Golshayan D, Ehirchiou D, Wass JC, Giovannoni L, Meier R, Serre-Beinier V, Puga Yung G, Morel P, *Bühler L, *Seebach JD. Immunosuppressive effects of streptozotocin-induces diabetes result in absolute lymphopenia and a relative of T regulatory cells. Diabetes 2011 60:2331-2340
Schwitzguébel AJ, Jandus P, Lacroix J-S, *Seebach JD, *Harr T. Immunoglobulin deficiency in chronic rhinosinusitis: systematic review of the literature and meta-analysis. *Both last authors contributed equally to this work. J Allergy Clin Immunol. 2015;136:1523-31
Papaserafeim M, Jandus P, Ferfoglia RI, Nieke JP, Vonarburg C, Spirig R, Yung GP, Seebach JD. Effect of intravenous immunoglobulin G therapy on natural killer cell function related to Fc gamma receptor gene expression. J Allergy Clin Immunol. 2020:S0091-6749(20)30485-1
28 Oct 2020