Celiac markers unaffected by diet, proteomic analysis reveals

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A proteomic analysis of plasma proteins has identified two diet-independent markers for celiac disease, potentially transforming how the condition is diagnosed.
 
“The results of this study have the potential to significantly impact clinical care,” first author Isabel A. Hujoel, MD, of the Division of Gastroenterology at the University of Washington, Seattle, told GI and Hepatology News. “Adopting a gluten-free diet without a clear diagnosis of celiac disease is common in the US. Unfortunately, once gluten-free, it is not currently possible to determine if someone has celiac disease without doing a gluten challenge.”
 
A gluten challenge requires consuming a substantial amount of gluten over a prolonged period. Many people are reluctant to do this because of the symptoms that gluten can trigger, which makes it difficult to confirm whether they have celiac disease, said Dr. Hujoel. “Identifying markers for celiac disease that are invariant to diet would allow people to bypass the gluten-challenge and to obtain a proper diagnosis.”
 
Using data from the UK Biobank, the researchers, conducted a proteomic study to identify plasma proteins associated with celiac disease in individuals following a gluten-free diet. They used ICD-10 code K90.0 to identify celiac disease cases and limited the study to individuals who had been diagnosed before their blood samples were collected. They standardized protein levels to reduce extreme values and then compared these levels between individuals with celiac disease on a gluten-free diet and healthy controls, according to their research published in Gastro Hep Advances.
 
A total of 1,044 participants had been diagnosed with celiac disease before proteomic testing. Of these, 141 completed a dietary questionnaire, and 132 reported following a gluten-free diet. Four proteins were significantly elevated in this group: anterior gradient 2, carboxypeptidase A2 (CPA2), integrin subunit beta 7 (ITGB7), and POF1B actin-binding protein (POF1B). However, only two — CPA2 and ITGB7 —appeared to be specific to celiac disease.
 
“I was excited to find not just one but four markers that were invariant to diet,” Dr. Hujoel said. “The ability to diagnose celiac disease in those on a gluten-free diet without requiring a gluten-challenge is one of the most common hopes that I hear from patients in my clinical practice. I see many patients in clinic who are frustrated by the lack of available testing to help them obtain a diagnosis without suffering the symptoms of gluten consumption.”
 
Before this discovery, the authors highlighted the HLA-DQ–gluten tetramer as the most promising alternative to the gluten challenge, noting that research indicates it can reliably detect celiac disease even when gluten is not being consumed. “Unfortunately, this test is limited by not being commercially available, requiring a significant volume of blood to perform, and being labor-intensive,” wrote Dr. Hujoel and colleagues.
 
She acknowledged certain limitations of the proteomic analysis, including that gluten-free diet was determined based on survey responses and that celiac disease may have been misclassified through ICD coding. “Our findings are preliminary and only suggest possible markers for celiac disease that are invariant to diet,” she emphasized. “Our findings need to be confirmed with further studies and clinical trials.”
 
The authors reported having no relevant disclosures.

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