Editors' ChoiceAutoimmune Disease

Interception! A decoy scaffold disrupts autoimmunity

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Science Translational Medicine  18 Sep 2019:
Vol. 11, Issue 510, eaaz2899
DOI: 10.1126/scitranslmed.aaz2899


Subcutaneous implantation of microporous collagen scaffolds decorated with a model autoantigen prevents onset of autoimmune encephalomyelitis in mice.

Relapsing-remitting autoimmune diseases, such as multiple sclerosis, are characterized by the generation of autoantigen-specific responses in secondary lymphoid organs and the trafficking of effector immune cells to antigen-rich tissues where they mount an acute adaptive immune response. This is followed by immune cell exhaustion and return to secondary lymphoid organs, where the cycle repeats. Immunotherapies that block this migratory circuit have exhibited great success in the clinic; however, these treatments are nonspecific, resulting in detrimental systemic and off-target effects. Antigen-specific therapies for autoimmune disorders would enable targeted abrogation of the disorder and could potentially eliminate the risk of off-target effects.

A new study published in Biomaterials reports the engineering of an antigen-decorated collagen scaffold, termed an “antigen-specific immune decoy (ASID)”, designed to intercept autoreactive immune cells before they can target host tissue for destruction. Subcutaneously implanted ASIDs prevented the onset of symptoms in a mouse model of autoimmune encephalomyelitis when implanted a week after disease initiation; intriguingly, this strategy also prevented symptoms during the relapse phase, despite complete ASID degradation prior to the expected relapse period. Mechanistic studies indicated that immune effector cells were exhausted and apoptotic locally within the ASID and were reduced systemically.

One caveat of this work is that the investigators only explored the efficacy of this treatment on presymptomatic mice. Diagnosis of multiple sclerosis in humans occurs well after disease onset, and it is unclear whether treatment could prevent relapse if administered after a prolonged manifestation of symptoms. Another caveat is the simplicity of the mouse model used, in which a single known antigen stimulates autoimmunity; it is unclear how closely this model recapitulates human autoimmune disorders, in which multiple autoantigens are implicated. Last, there are potential safety concerns with generating a concentrated depot of antigen to stimulate effector cells. Indeed, the authors note that they expected a heightened immune response during the relapse phase due to hypersensitivity of immune cells toward the antigen. They hypothesize that the high density of antigen within the collagen scaffold induced overstimulation and cell death, preventing immune onslaught during the relapse phase. Despite these caveats, if this interesting and novel approach can be translated to the clinic, there is potential for broad impact for patients with relapse-remitting autoimmune disorders, ranging from multiple sclerosis to rheumatoid arthritis to type 1 diabetes.

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