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Stanford Group Develops Autoantigen Arrays to Target Autoimmune Diseases


In what may be a preliminary step towards developing multiplex screening tests for autoimmune diseases, researchers at Stanford University and their colleagues have built autoantigen microarrays. These arrays, which the researchers described in a March Nature Medicine article, are designed to be used with a sub-microliter quantity of patient serum sample, and to characterize autoantibodies related to these disorders. The researchers claimed that theirs is the first report in which protein arrays were applied to multiple human disease sera.

The scientists spotted 196 different autoantigens, including proteins, peptides and DNA, onto derivatized glass slides to yield arrays with 1,152 features. These autoantigens covered eight different human autoimmune diseases, including systemic lupus erythematosus and rheumatoid arthritis. The researchers then incubated the arrays with patient serum samples, and detected autoantibodies using fluorescently labeled secondary antibodies. They found that the antigen arrays were more sensitive compared to conventional ELISA.

“Right now clinicians test each antigen separately — and each one can take weeks,” P.J. Utz, assistant professor of immunology and rheumatology and senior author on the study, said in a statement. “These arrays could enable a clinician to diagnose the disease on the first visit.”

Utz and William Robinson, a fellow in the division of immunology and rheumatology and lead author on the paper, are looking to isolate the autoantbodies for all autoimmune diseases. They also foresee that the arrays could actually aid in the development of antigen-specific therapies tailored to the individual patient.

“Prescribing currently available drugs for autoimmune diseases is like taking a sledgehammer to the immune system,” Robinson said. “Antigen-specific therapies will leave the global immune system in place.”

The authors noted, however, that some of the autoantigens were not detected using the array system, probably because these molecules lost their native structure while captured on the arrays. “An important direction for refinement of this method is improvement of surfaces and conditions for attachment of structurally and chemically heterogeneous autoantigens,” they wrote.

— JK

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