Editors' ChoiceAutoimmune Disease

Lather, rinse, repeat for giant results

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Science Translational Medicine  19 Oct 2016:
Vol. 8, Issue 361, pp. 361ec165
DOI: 10.1126/scitranslmed.aai9163

Circulating antibodies that bind self-antigens (autoantibodies) are considered important drivers of disease, including autoimmune disorders, infections, and cancers. They may offer peripheral windows into the immune response during disease progression or treatment. Technologies that readily measure the breadth and depth of autoantibody formation in patient specimens could provide biological or clinical insight to inform management.

Lee et al. developed reusable protein microarrays to detect autoantibodies via peptides immobilized on giant magnetoresistive (GMR) nanosensors, at a resolution of a single posttranslationally modified amino acid. As proof-of-concept, the researchers applied antibody-containing sera from healthy volunteers and patients with systemic lupus erythematosus (SLE) onto their microarrays, combined with biotinylated secondary antibodies and streptavidin-coated magnetic nanoparticles (MNPs). Magnetic fields generated from bound MNPs caused changes in electrical resistance that were detected by the GMR sensors underneath. The researchers also demonstrated that (i) sensors could be regenerated by rinsing with commercially available surface plasmon resonance buffers, allowing for repeat sensing, and (ii) peptides could be synthesized in situ on sensor surfaces using optical lithography. These advances address limitations of protein microarrays. Reusable sensors reduce experimental costs and circumvent inter-microarray variation. Use of peptides leverages their durability under harsh regeneration conditions compared with protein ligands. The authors directly synthesized peptides on GMR nanosensors to provide higher packing density.

Reusable GMR sensors offer some advantages over alternative modalities. The absence of photobleaching allows for continuous measurements to assess binding dynamics. Their all-electrical measurements promote compact design strategies for device miniaturization and high-throughput testing at the point of care. Reusable sensors should also decrease cost, although true reduction will require improved mass production techniques. Microfabricated GMR chips are produced from specialized and costly wafers. Use of larger wafers with smaller sensor arrays could decrease unit costs per chip. Once scaled, the technology is positioned to examine autoantibodies as potential diagnostic or response biomarkers. Although the authors focused on SLE, the technology's impact transcends disease states. For example, testing autoantibody panels could highlight mechanisms behind the promising yet varied responses to immunotherapies in oncology, including emergence of antidrug antibodies and their effects on drug resistance and toxicities.

J.-R. Lee et al., High-resolution analysis of antibodies to post-translational modifications using peptide nanosensor microarrays. ACS Nano 10.1021/acsnano.6b03786 (2016). [Abstract]

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