Unveiling trogocytosis: A breakthrough in understanding antibody-mediated immune suppression

This blog was written with the assistance of Canadian Blood Services senior scientist, Dr. Alan Lazarus.

In transfusion science, groundbreaking discoveries continually reshape our understanding of the human body's intricate mechanisms. One such revelation has emerged from a recent scientific article titled "Trogocytosis drives red blood cell antigen loss in association with antibody-mediated immune suppression" authored by Dr. Yoelys Cruz-Leal, a postdoctoral fellow working with Canadian Blood Services senior scientist Dr. Alan Lazarus, along with doctoral student Peter A. A. Norris and additional colleagues at the Keenan Research Centre for Biomedical Science, St. Michael’s Hospital. This study delves into the underlying mechanisms of antibody-mediated immune suppression (AMIS), a phenomenon where certain antibodies stop an immune response, and introduces the concept of trogocytosis as a pivotal player in the associated loss of red blood cell (RBC) antigens.  

Hemolytic disease of the fetus and newborn

Hemolytic disease of the fetus and newborn (HDFN) is a serious condition where maternal antibodies target and destroy fetal RBCs. This can lead to a range of symptoms for the fetus (during pregnancy), and newborn (after birth), including miscarriage or neonatal death in severe cases. Where risk of HDFN is identified, prevention of HDFN includes the use of anti-D, also known as RhIg, which is a product made from pools of human plasma (see Chapter 12 of the Clinical Guide to Transfusion for more information). The mechanism through which anti-D works to prevent HDFN is antibody-mediated immune suppression (AMIS). However, the precise mechanisms underlying AMIS have long eluded researchers. 

Traditionally, the scientific community has centered its attention on the rapid clearance of RBCs (i.e., removal of RBCs from the bloodstream) as the primary mechanism of AMIS. However, recent studies, including the one highlighted in this blog post, have brought about a paradigm shift. The research introduces the idea that RBC antigen loss, specifically through trogocytosis, may play a crucial role in AMIS, challenging the conventional belief of RBC clearance. 

Trogocytosis

The study explored various antibodies' abilities to induce AMIS, focusing on their impact on RBC clearance, antigen loss, and RBC membrane loss. The results were groundbreaking, indicating that AMIS could be triggered independently of RBC clearance, yet consistently causing significant loss of RBC antigens. In addition, anti-D itself was also tested and demonstrated to induce trogocytosis. This led to the proposal that trogocytosis, a mechanism involving the transfer of membrane fragments between cells, could be a major contributor to AMIS. 

The discovery that trogocytosis drives RBC antigen loss in association with AMIS represents a significant leap forward in our comprehension of immune responses by challenging the traditional focus on RBC clearance. It also highlights the need for a nuanced approach in designing therapeutic interventions, opening doors to innovative approaches that could redefine how we combat immune-mediated disorders. 

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The opinions reflected in this post are those of the author and do not necessarily reflect the opinions of Canadian Blood Services nor do they reflect the views of Health Canada or any other funding agency.