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In autoimmune dis­eases, the human body’s own defense system turns against itself, attacking healthy cells and their protein com­po­nents. 

Junior Christine Aush­erman spent her summer at the Van Andel Research Institute as part of their Frederik and Lena Meijer Summer Internship Program, where she worked on a new method to pin­point which pro­teins are being attacked.

Ausherman’s work focused on lupus, a disease in which the immune system’s anti­bodies — part of a defense mech­anism that nor­mally fights bac­teria and viruses — fail to dis­tin­guish between foreign invaders and healthy tissue and attack the body’s own pro­teins.

This autoimmune response can cause a variety of symptoms ranging from fatigue and joint pain to kidney inflam­mation. As many as five million people worldwide have a form of lupus, and approx­i­mately 16,000 new cases are reported each year, according to the Lupus Foun­dation of America.

For her summer research, Aush­erman worked with a spe­cific tool called a peptide microarray, which allows researchers to test an antibody’s inter­action with a variety of dif­ferent pro­teins at once.

“Peptide microarrays are spe­cialized glass micro­scope slides that display mod­ified forms of pro­teins on the slide surface at very high density,” said Scott Rothbart, assistant pro­fessor in the Van Andel Research Institute’s Center for Epi­ge­netics and lead inves­ti­gator in the lab where Aush­erman worked. “This allows us to monitor upward of 10,000 indi­vidual inter­ac­tions simul­ta­ne­ously and com­par­a­tively on a single slide.”

To test for protein-antibody inter­action, the glass slide is flooded with an antibody. If the antibody attacks a par­ticular type of protein, it will bind to the protein on the slide, while pro­teins unaf­fected by the antibody will remain untouched. Attached to the anti­bodies are flu­o­rescent mol­e­cules that allow the researchers to see which pro­teins attracted the anti­bodies.

“Then, we can look at the plate and see where the antibody binds,” Aush­erman said. “The antibody is flu­o­res­cently labelled, so if the antibody binds, that area will light up under a flu­o­rescent scanner.”

Ausherman’s microarrays focused on his­tones, a type of protein that helps package and store the cell’s DNA and can be attacked by anti­bodies in lupus patients.

“It’s been known for a while that anti­bodies against histone pro­teins are markers of autoimmune dis­eases like lupus and rheumatoid arthritis,” Rothbart said.

Using the histone peptide microarrays, Aush­erman tested anti­bodies from lupus patients’ blood and com­mercial anti­bodies for their response to dif­ferent his­tones. 

While she focused on the four most common types of his­tones, these his­tones can be mod­ified in many ways with dif­ferent chemical tags, and the tags will affect their inter­ac­tions with anti­bodies, Aush­erman said.

By using anti­bodies from lupus patients, Aush­erman was able to see if there was a common antibody response among the patients to par­ticular mod­ified forms of histone pro­teins.

“The goal of the project was to determine the utility of this new tool for the capture of anti­bodies from patients with lupus,” Rothbart said. “The histone peptide microarray is a platform we’ve helped develop over the last few years, and the capture of these anti­bodies is a new use for this tool.”

While Rothbart said more work is needed to establish this microarray tech­nique as a way to screen patient samples, he is opti­mistic that further work will allow the tech­nique to be used as a clinical diag­nostic and staging tool or as a way to identify new bio­markers for autoimmune dis­eases such as lupus and rheumatoid arthritis. He said the tech­nique may ulti­mately be applicable to cancer, too.

“Where we’d ulti­mately like to go is to explore the use of this tech­nology in cancer,” Rothbart said. “We’re a cancer epi­ge­netics lab, and so I think an unex­plored space in this area is the preva­lence of histone anti­bodies in patients with tumors. With proof-of-concept that this platform works with autoimmune cases, we’re excited for the prospect of applying this tech­nology to other dis­eases as well.”