Individuals with very few platelets (the blood cells that regulate blood clot formation) are said to suffer from thrombocytopenia. There are many causes of thrombocytopenia, including increased destruction of platelets.
New data, generated by two independent groups, have provided clinically relevant insight into two forms of thrombocytopenia caused by increased platelet destruction — immune thrombocytopenic purpura (ITP) and fetomaternal alloimmune thrombocytopenia (FMAIT). The importance of these studies for the development of new therapeutics is discussed in an accompany commentary by Bethan Psaila and James Bussel, at Weill Cornell Medical College of Cornell University, New York.
In the first study, Masataka Kuwana and colleagues, at Keio University School of Medicine, Japan, set out to understand why platelet numbers return to nearly normal levels in about 50% of individuals with ITP who are also infected with the bacterium Helicobacter pylori after they have been treated with antibiotics to clear their H. pylori infection. It was found that immune cells known as monocytes (which are involved in the destruction of platelets through their ability to take up and degrade antibody coated platelets via activating Fc receptors) exhibited characteristics of activated cells before the H. pylori infection was eradicated.
This included high levels of activating Fc-gamma receptors and low levels of an inhibitory Fc-gamma receptor. Upon H. pylori eradication levels of the activating Fc-gamma receptors decreased and levels of the inhibitory receptor increased. The authors therefore conclude that H. pylori eradication dampens the activation status of monocytes such that their Fc-gamma repertoire favors uptake and destruction of platelets and that this is reversed upon H. pylori eradication.
In the second study, Cedric Ghevaert and colleagues, at NHS Blood and Transplant, United Kingdom, developed an approach to manipulate the interaction between antibody coated platelets and activating Fc-gamma receptors to decrease monocyte uptake and destruction of platelets. In FMAIT, mothers generate antibodies that bind to a molecule (HPA-1a) on the platelets of their fetus such that they are taken up by monocytes and destroyed.
The authors developed a molecule that binds HPA-1a in place of the mother's antibodies when analyzed in vitro. Further in vitro and mouse studies indicated that this molecule dramatically decreased platelet destruction, leading to the suggestion that this approach be evaluated in human clinical studies.
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