Intravenous immunoglobulins induce CD32-mediated platelet aggregation in vitro.
BACKGROUND
Intravenous immunoglobulins (IVIg) and cytomegalovirus immunoglobulins (CMVIg) are currently finding increased acceptance in clinical states of high immune activity and in transplant recipients. A rare side-effect of their application is intravascular thrombosis, which is thought to be related to pre-existing hyperviscosity. In a previous study we have shown that rabbit antithymocyte globulin causes platelet aggregation in vitro via the Fc IgG receptor (CD32).


OBJECTIVE
To investigate if IVIg and CMVIg have the potential to cause CD32-dependent platelet aggregation.


METHODS
The influence of CMVIg or IVIg on platelets pre-incubated with or without monoclonal antibody AT10 was studied in an aggregometer. Expression of platelet surface activation marker CD62P was determined by fluorescence-activated cell sorting analysis and presence of soluble CD40L (sCD40L) was evaluated by enzyme-linked immunosorbent assay. All in vitro experiments were performed using platelet concentrates from the blood bank, at therapeutic concentrations of immunoglobulins. Results Incubation of platelets with CMVIg and IVIg markedly induced platelet aggregation, and increased expression of CD62P and secretion of sCD40L. The capacity of CMVIg and IVIg to induce platelet aggregation was completely abrogated by adding the blocking antibody AT10 directed against the low-affinity Fc IgG receptor (CD32).


CONCLUSIONS
Our results suggest that CMVIg and IVIg solutions with activating Fc domains are able to bind CD32 on platelets and cause platelet aggregation in vitro. These results indicate a mechanism by which in vivo intravascular thrombosis may be explained and suggest caution with concomitant use of packed platelets and IVIg in autoimmune diseases in the clinical setting.
Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
A
A
Pollreisz
A
A
Assinger
S
S
Hacker
K
K
Hoetzenecker
W
W
Schmid
G
G
Lang
M
M
Wolfsberger
B
B
Steinlechner
E
E
Bielek
E
E
Lalla
W
W
Klepetko
I
I
Volf
H J
HJ
Ankersmit
D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D023201:CD40 Ligand / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism; D002478:Cells, Cultured; D000078842:Cytoglobin; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005914:Globins / Q000494:pharmacology; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology; D007075:Immunoglobulin M / Q000494:pharmacology; D007136:Immunoglobulins / Q000494:pharmacology; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D008854:Microscopy, Electron; D015539:Platelet Activation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D017452:Receptors, IgG / Q000032:analysis*; D013268:Stimulation, Chemical
D000078842:Cytoglobin; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D017452:Receptors, IgG; C045781:cytomegalovirus-specific hyperimmune globulin; D023201:CD40 Ligand; D005914:Globins; C060166:pentaglobulin