Editors' ChoiceAutoimmune Disease

Preempting autoimmune disease with induced antigen tolerance

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Science Translational Medicine  22 Mar 2017:
Vol. 9, Issue 382, eaan0764
DOI: 10.1126/scitranslmed.aan0764

Abstract

Transfusion of red blood cells with antigenic peptides added to surface proteins is being explored as a tolerance-inducing intervention for autoimmune disease.

Available treatments for autoimmune disease have broad immunosuppressive properties and major side effects. Pishesha et al. hypothesized that induction of tolerance to specific peptide antigens could modify the course of autoimmune disease without generalized immunosuppression. During phagocytic processing of red blood cells (RBCs) in the spleen, a peptide antigen added to an RBC protein would be considered “self” generating antigenic tolerance. The authors thus tested transfusion of RBCs modified with peptide antigens as a potential therapy for autoimmunity.

“Blood donor” mice were generated by appending a terminal LPETGG peptide to Kell proteins on RBCs. Transgenic mice infused with antigen-specific B or T cells and then transfused with antigen-modified RBCs had fewer antigen-specific B or T cells, respectively, in the spleen after antigen challenge. In the B cell model, antigen-specific antibodies were not detected by Western blot. In the T cell models, there were increased markers of lymphocyte exhaustion.

In mouse experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, induced by myelin oligodendrocyte glycoprotein (MOG35-55), C57BL/6 mice were pretreated with RBC-MOG35-55 (RBCs carrying MOG35-55) before induction of EAE. This delayed the onset of disease, with decreases in lymphocytic infiltration and demyelination in the spinal cord. Mice that were transfused during the incubation period after the initial exposure to the antigen also had delayed onset of disease. In a mouse model of diabetes, where destruction of pancreatic islets is mediated by immune response to insulin B-chain peptide (Ins9-23), transfusion with RBC-Ins9-23 decreased the destruction of pancreatic islets.

These findings are intriguing, and consideration of RBC-antigen transfusion for human autoimmune disease merits further study. Future work on this method should assess antigen dose response, cross-tolerance with related peptides, impact of hemoglobinopathy or RBC abnormalities, potential induction of autoimmune hemolytic anemia, and transfusion reactions.

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