Background/Case Studies: Due to the high frequency of disease- or treatment-related thrombocytopenia, hematologic disorders require treatment with multiple platelet transfusions, which can trigger a humoral response directed against platelets. Platelet concentrates (PCs) contain many immunomodulatory elements, including the platelets themselves, and also extracellular vesicles budding from platelets, known as platelets microparticles (PMPs). Platelet transfusion is associated with adverse effects, including alloimmunization and PMPs play an important role in immunomodulatory processes. Mechanisms of HLA alloimmunization are few described. It is only known that CD4+ T lymphocytes (TLs) play a key role. We have no information on the role of APCs (DCs or monocytes) or B lymphocytes responsible for these HLA alloantibodies. We hypothesize that PMPs interact with immune system cells by facilitating their activation, and ultimately humoral production.
Study
Design/Methods: To address this hypothesis, we studied the interaction of PMPs with DCs, monocytes, CD4+ TLs, CD8+ TLs and B lymphocytes. Sorted by flow cytometry, different doses of CD41a+ MPs were cultured with these cells. Functional studies were conducted 18 hours after these interactions.
Results/Findings: We showed that the binding sensibility of CD41a+ expressing MPs is different between cells. APCs are more likely to bind CD41a+ MPs than TLs. Although functional activation is thus associated with the amount of CD41a+ MPs in culture, all cells studied show polyclonal functional activation after co-culture with CD41a+ MPs, including immunoglobulin production. Conclusions: Alloimmunization against platelets leading to platelet refractoriness is an important challenge in the practice of platelet transfusion. Fortunately, it has long been known that alloimmunization is not systematic, and anti-HLA antibodies does not necessarily induce platelet refractoriness. The exact role of CD41a+ MPs in vivo is not yet formally established. Indeed, to understand alloimmunization, we must consider the immunological profile of the transfused patients. However, ur pioneer results indicate that CD41a+ MPs are at least partly responsible for the activation of the immune system. Moreover, as the interactions of CD41a+ MPs are more beneficial to APCs, that supports the idea of new therapeutic perspectives for targeted antigen delivery for vaccination purposes.
Importance of research: Transfusion-related immunoregulation is few studied, although transfusions are in many cases applied to patients with pathologies involving immune system dysregulation. The non-exosomal extracellular microvesicles of blood concentrates play a major role in the regulation of the immune system of transfused patients. This study reinforces the role of these microvesicles in this theme.
