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according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
Patients with positive celiac serologies but normal villous architecture on biopsy are considered to have potential celiac disease (PCD). While the prevalence of PCD is not well-established, it is estimated to be around 1%. This study by Auricchio and colleagues investigates seven serum proteomic biomarkers that could help predict whether asymptomatic patients with PCD are at risk of developing villous atrophy (VA).
The study also identifies specific inflammatory proteins present in PCD patients who are likely to develop VA. These biomarkers provide valuable insights into the pathogenesis of celiac disease and the development of VA in genetically predisposed individuals.
As celiac disease is increasingly diagnosed without biopsies, serum proteomic biomarkers could be crucial in identifying patients who may benefit from starting a gluten-free diet (GFD) earlier, potentially preventing complications. According to the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) guidelines, children can be diagnosed with celiac disease if their tissue transglutaminase IgA level is 10 times the upper limit of normal, confirmed by a positive endomysial antibody test. However, this approach may lead to many patients committing to a lifelong GFD despite having only PCD, as biopsies may not have been performed. In this study, 60% of patients with PCD did not progress to VA, suggesting that biomarkers could help prevent unnecessary long-term GFD commitments.
Stephanie M. Moleski, MD, is the director of the Jefferson Celiac Center and associate professor in the division of gastroenterology at Thomas Jefferson University Hospital in Philadelphia. She reported no conflicts of interest.
according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
according to investigators.
Given that PCD patients present with positive serology and intact duodenal architecture, these findings may provide a much-needed tool for identifying patients who are more likely to benefit from early dietary interventions, lead author Renata Auricchio, MD, PhD, of the University of Naples Federico II, Italy, and colleagues reported.
“PCD offers the unique opportunity to observe the progression of gluten-induced tissue damage in celiac disease,” the investigators wrote in Gastroenterology. “These patients recognize gluten and produce specific autoantibodies, but have not developed intestinal damage.”
The study included 31 children with asymptomatic PCD who were eating a gluten-containing diet. Serum samples from each child were analyzed for the relative abundance of 92 inflammation-linked proteins using a proximity extension immunoassay. Statistical analyses, including partial least squares discriminant and linear discriminant analyses, were then applied to identify which proteins were associated with the development of VA.
After a mean follow-up period of 5.85 years, 14 participants developed VA (ie, celiac disease), while the remaining 17 remained asymptomatic.
Panel analysis revealed that specific inflammatory proteins, including interleukin (IL)–20, IL-2, sirtuin 2 (SIRT2), leukemia inhibitory factor (LIF), IL-22 receptor subunit a1, cystatin D (CST5), IL-17 receptor A, IL-15 receptor subunit a (RA), CUB domain–containing protein 1 (CDCP1), and IL-14, were 1.23- to 1.76-fold higher in children who developed VA. Among these, seven proteins — CDCP1, IL-2, LIF, IL10RA, SIRT2, CST5, and IL-4 — were able to significantly distinguish between symptomatic and asymptomatic cases in a linear discriminant model. This panel of seven proteins achieved a predictive accuracy of 96.8% in identifying children at risk of VA.
Additionally, bioinformatics pathway analysis confirmed that the broader set of proteins is involved in the positive regulation of JAK-STAT signaling (involving IL-22 receptor subunit a1, IL-4, IL-20, IL10RA, LIF, and IL-2), inflammatory responses (IL-4, IL-20, LIF, and IL-2), and processes such as tyrosine phosphorylation, leukocyte differentiation, IgG isotype switching, and protein phosphorylation regulation. These findings suggest that gluten-induced inflammation may already be active in early stages of the disease, including the initial phases of leukocyte differentiation, according to the investigators.
“Over a long follow-up on a gluten-containing diet, only 40% of these patients progressed to VA,” Dr. Auricchio and colleagues wrote. “Notably, 25%-30% of children with PCD even stop producing anti–tissue transglutaminase antibodies, and the others keep on producing autoantibodies but preserve a normal intestinal mucosa. Considering these data, the decision to address a patient with PCD on a gluten-free diet at time of diagnosis is quite critical.”
The researchers noted that this new model, with accuracy exceeding 95%, is well suited for routine use because of its practicality and reliability.
“Our previous model, based mainly on small intestinal mucosa features, moved a step toward the prediction of outcome but still required a mucosal biopsy, and the accuracy of prediction was not greater than 80%, which is somewhat uncertain for a lifelong clinical decision,” they wrote. In contrast, the present model “appears to be sufficient to immediately suggest a gluten-free diet in children with PCD, who are almost certainly committed to developing VA.”
The investigators called for long-term studies to validate their findings in other cohorts, including adult populations.This study was supported by the TIMID project and Inflammation in Human Early Life: Targeting Impacts on Life Course Health (INITIALISE) by the Horizon Europe Program of the European Union. The investigators disclosed no conflicts of interest.
FROM GASTROENTEROLOGY