Immunomodulatory Properties of Packed Red Blood Cells during Storage

Eva Laurén; Lotta Sankkila; Ville Pettilä; Erja Kerkelä

doi:10.1159/000525706

Immunomodulatory Properties of Packed Red Blood Cells during Storage

Transfus Med Hemother. 2022 Nov 4;50(3):208-217. doi: 10.1159/000525706. eCollection 2023 Jun.

Authors

Eva Laurén^{1

2}, Lotta Sankkila¹, Ville Pettilä², Erja Kerkelä¹

Affiliations

¹ Finnish Red Cross Blood Service, Helsinki, Finland.
² Department of Intensive Care Medicine, Department of Anesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Abstract

Introduction: Red blood cell (RBC) transfusion may affect the recipient immune system. During RBC storage in an unphysiological environment, RBC quality and function are impaired, the cells bleb extracellular vesicles (EVs), and other bioactive substances accumulate in the storage medium. EVs can carry reactive biomolecules and mediate cell-cell interactions. Thus, EVs could explain RBC transfusion related immunomodulation, particularly after prolonged storage.

Methods: We exposed peripheral blood mononuclear cells (PBMCs) to allogeneic RBC supernatant (SN) and EVs from fresh and longer-stored RBC units, diluted plasma, and storage solution SAGM, and studied activation and proliferation of T-cells by flow cytometry, and cytokine secretion of LPS-stimulated PBMCs by enzyme-linked immunosorbent assay (ELISA).

Results: Both fresh and longer-stored RBC SN but not EVs induced immunomodulation in recipient cells. RBC SN and diluted plasma augmented the proliferation of particularly CD8⁺ T-cells in a 4-day proliferation assay. T-cell activation by SN was evident already after 5 h as shown by upregulation of CD69. SN suppressed monocyte TNF-α and increased IL-10 secretion while diluted plasma increased secretion of both cytokines.

Conclusion: This in vitro study demonstrates that stored RBC SN will have mixed immunomodulatory effects depending on responder cells and conditions, independent of RBC storage age. Fresh RBCs containing relatively few EVs can induce immune responses. Residual plasma in the products may contribute to these effects.

Keywords: Extracellular vesicles; Red blood cells; T-cell proliferation; Transfusion-related immunomodulation.

Grants and funding

This study was supported by the Finnish Funding Agency for Innovation (TEKES) as part of SalWe research program Personalized Diagnostics and Care (GET IT DONE, Grant No. 3986/31/2013), and Clinical Research funding (EVO/VTR) from Helsinki University Hospital.