Functional dissection of C-reactive protein’s role in exacerbating destruction of blood cells (LSBR 1527)
Project leader: Dr. Gestur Vidarsson, Department of Experimental Immunohematology / Immunoglobulin research lab, Sanquin Research, Amsterdam
PhD student: Robin Temming (May 2016 – May 2020)
Technician: Remco Visser (Jan. 2017 – July 2017 (75%))
Technician: Arthur Bentlage (Jan. 2018 – June 2019)
In this project, we followed up previous work suggesting that inflammation, more particularly the acute phase response leading to elevated C-Reactive Protein (CRP) levels, can exacerbate symptoms in
antibody mediated disorders when they target platelets causing thrombocytopenia’s. This can be caused by autoimmune reactions, or alloimmune reactions in pregnancy, or after blood transfusions.
We now systematically investigated how this occurs, and if this is also occurring for clearance of Red Blood cells. Our results show that Immunoglobulin receptors on myeloid cells in particular (IgG-Receptors(FcγR) but also IgA (FcαR)) seem to bind CRP. On activated neutrophils with FcγRI expression, mimicking neutrophils we see in acute phase responses, are particularly sensitive to elevated CRP levels, causing elevated RBC phagocytosis in vitro. This may explain why inflammation
is a negative-prognostic factor, showing less recovery of transfused RBC and platelets. We also show
that CRP also can be used to improve antibody-mediated killing of tumor cells in-vitro, something that might be exploited in future tumor therapies.