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Researchers identify autoantibody biomarkers in Crohn's disease using immunoproteomics
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Researchers from the Arizona State University Biodesign Institute and Mayo Clinic have identified autoantibody biomarkers in Crohn’s disease using a novel immunoproteomics strategy.
This finding could lead to improved diagnosis, understanding and management of the inflammatory bowel disease, and supports the utility of immunoproteomics for identifying antibody biomarkers, they wrote.
“If we are going to truly alter the natural history of Crohn’s disease and help people, we needed to develop a new test for early, accurate diagnosis, as well as administrating appropriate therapy,” Josh LaBaer, MD, PhD, the interim executive director of the Biodesign Institute, said in a press release. “We are particularly excited about the links between the immune response against self proteins and Crohn’s disease, as this may give physicians a new avenue to explore both the potential cause and treatments.”
Josh LaBaer
LaBaer and colleagues, including Ji Qiu, PhD, advanced the novel immunoproteomics strategy to perform a broad search for Crohn’s markers throughout the whole span of immune system proteins found in human blood.
“There has been increasing evidence that suggests the Crohn’s disease immune response may be a result of altered microbes in the gut or exposure to harmful toxins that will result in antibodies against microbial and human proteins being made that are very specific manifestation of the disease,” Qiu said in the press release. “Many blood-based biomarkers have been discovered, but currently commercially available blood tests have not been widely adapted into clinical practice because they fail to accurately diagnose Crohn’s disease.”
To identify autoantibodies associated with Crohn’s disease, investigators evaluated serum samples from 48 patients with Crohn’s disease and 48 age- and sex-matched controls identified within Mayo Clinic Arizona and Rochester Biobanks. They identified several candidates of both IgG and IgA autoantibody classes in the discovery cohort and validated them in a separate validation cohort with the same number of patients and controls.
Then they profiled the validated autoantibody candidates against about 1,900 human proteins from LaBaer’s human gene collection bank, using a novel protein array technology called nucleic acid programmable protein arrays, or NAPPA. This involves technology that “avoids making ... arrays by timely and costly protein purification, but rather, by making fresh protein at the time of the test from a more stable DNA copy on the slide,” according to the press release.
They found that IgG autoantibodies showed stronger reactivity than IgA autoantibodies, but the latter showed more differential reactivity in Crohn’s patients vs. controls. They newly identified four IgA autoantibodies against SNRPB, PRPH, PTTG1 and SNAI1 with greater than 15% sensitivity and 95% specificity.
Anti-SNRPB-IgA showed the greatest sensitivity (24%), which “has also been reported in Lupus patients, known as the ‘Smith antigen,’” according to the press release. The investigators also identified autoantibodies linked to specific disease subtypes.
It is possible that “these antibodies reflect dysregulated immune response in the gut [or] they could play a pathogenic role,” LaBaer said in the press release. “But so far, we simply don’t have enough such antibodies discovered to understand their functional role.”
Next, he and colleagues plan to perform expanded studies of autoantibodies and antimicrobial antibodies against microorganisms related to Crohn’s disease.
“Ultimately, we know that no single biomarker is going to be predictive and meet clinical needs,” he said in the press release. “Only a panel of biomarkers, made of individually validated biomarkers, will achieve the best performance in the clinic. But we are excited about the potential of this immunoproteomics approach for Crohn’s disease and will work to discover additional biomarkers.” – by Adam Leitenberger
Disclosures: Healio Gastroenterology was unable to confirm the researchers’ relevant financial disclosures at the time of publication.
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