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A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants

Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite g...

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Autores principales: Auricchio, R., Galatola, M., Cielo, D., Amoresano, A., Caterino, M., De Vita, E., Illiano, A., Troncone, R., Greco, L., Ruoppolo, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778072/
https://www.ncbi.nlm.nih.gov/pubmed/31586100
http://dx.doi.org/10.1038/s41598-019-50735-7
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author Auricchio, R.
Galatola, M.
Cielo, D.
Amoresano, A.
Caterino, M.
De Vita, E.
Illiano, A.
Troncone, R.
Greco, L.
Ruoppolo, M.
author_facet Auricchio, R.
Galatola, M.
Cielo, D.
Amoresano, A.
Caterino, M.
De Vita, E.
Illiano, A.
Troncone, R.
Greco, L.
Ruoppolo, M.
author_sort Auricchio, R.
collection PubMed
description Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite genetic and epigenetic studies, the pathological molecular mechanism remains unclarified. The strong genetic component does not explain more than half of the hereditability; we identified several epigenetic features that contribute to the understanding of the missing hereditability. The lipid profile of infants has been proposed as a potential biomarker of CeD metabolism that can be measured before they exhibit developmental disorders and clinical symptoms. We suggest that the state of the host is a main factor for the abnormal immune response to gluten. Long before any exposure to the offending agent or any production of specific antibodies, several molecular mechanisms are differentially expressed in infants who will develop CeD compared to their peers matched for the same genetic profile. The present study explored the serum phospholipid profile of a group of infants at risk for celiac disease, followed up to 8 years to monitor the onset of CeD. We compared 30 patients who developed the disease with 20 age- and sex-matched peers with similar genetic profiles who did not develop the disease within 8 years. Serum phospholipids were analysed at 4 months, before exposure to gluten, and at 12 months of age, when none showed any marker of disease. In the 30 CeD patients, we also analysed the serum at the time of diagnosis (>24 months). The serum phospholipid profile was fairly constant across 4 and 12 months of age and, in CeD, up to 24–36 months. The phospholipid signature was dramatically different in infants who developed CeD when compared to that of control NY-CeD (Not Yet developing Celiac Disease) peers. We identified a specific serum phospholipid signature that predicts the onset of celiac disease in HLA at-risk infants years before the appearance of antibodies specific for CeD in the serum and before any clinical symptoms, even before gluten introduction into the diet at 4 months. Specifically, lysophosphatidylcholine, phosphatidylcholine, alkylacyl-phosphatidylcholine, phosphoethanolamines, phosphatidylserines, phosphatidylglycerol and phosphatidylinositol were found to be differentially represented in CeD versus NY-CeD. A set constituted by a limited number of alkylacyl-phosphatidylcholine and lyso-phosphatidylcholine, together with the duration of breast-feeding, allows the discrimination of infants who develop celiac disease before 8 years of age from those at a similar genetic risk who do not develop the disease. In addition to recent discovery, our paper unveiled a specifc phopholipid profile, able to discriminate infants who eventually develop celiac disease years before antibodies or clinical symptoms ensue.
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spelling pubmed-67780722019-10-09 A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants Auricchio, R. Galatola, M. Cielo, D. Amoresano, A. Caterino, M. De Vita, E. Illiano, A. Troncone, R. Greco, L. Ruoppolo, M. Sci Rep Article Celiac disease (CeD) is a multifactorial disease influenced by both genetic and environmental risk factors. CeD genetic components are mainly due to HLA class II genes, which account for approximately 40% of the disease heritability. The environmental factor is linked to gliadin ingestion. Despite genetic and epigenetic studies, the pathological molecular mechanism remains unclarified. The strong genetic component does not explain more than half of the hereditability; we identified several epigenetic features that contribute to the understanding of the missing hereditability. The lipid profile of infants has been proposed as a potential biomarker of CeD metabolism that can be measured before they exhibit developmental disorders and clinical symptoms. We suggest that the state of the host is a main factor for the abnormal immune response to gluten. Long before any exposure to the offending agent or any production of specific antibodies, several molecular mechanisms are differentially expressed in infants who will develop CeD compared to their peers matched for the same genetic profile. The present study explored the serum phospholipid profile of a group of infants at risk for celiac disease, followed up to 8 years to monitor the onset of CeD. We compared 30 patients who developed the disease with 20 age- and sex-matched peers with similar genetic profiles who did not develop the disease within 8 years. Serum phospholipids were analysed at 4 months, before exposure to gluten, and at 12 months of age, when none showed any marker of disease. In the 30 CeD patients, we also analysed the serum at the time of diagnosis (>24 months). The serum phospholipid profile was fairly constant across 4 and 12 months of age and, in CeD, up to 24–36 months. The phospholipid signature was dramatically different in infants who developed CeD when compared to that of control NY-CeD (Not Yet developing Celiac Disease) peers. We identified a specific serum phospholipid signature that predicts the onset of celiac disease in HLA at-risk infants years before the appearance of antibodies specific for CeD in the serum and before any clinical symptoms, even before gluten introduction into the diet at 4 months. Specifically, lysophosphatidylcholine, phosphatidylcholine, alkylacyl-phosphatidylcholine, phosphoethanolamines, phosphatidylserines, phosphatidylglycerol and phosphatidylinositol were found to be differentially represented in CeD versus NY-CeD. A set constituted by a limited number of alkylacyl-phosphatidylcholine and lyso-phosphatidylcholine, together with the duration of breast-feeding, allows the discrimination of infants who develop celiac disease before 8 years of age from those at a similar genetic risk who do not develop the disease. In addition to recent discovery, our paper unveiled a specifc phopholipid profile, able to discriminate infants who eventually develop celiac disease years before antibodies or clinical symptoms ensue. Nature Publishing Group UK 2019-10-04 /pmc/articles/PMC6778072/ /pubmed/31586100 http://dx.doi.org/10.1038/s41598-019-50735-7 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Auricchio, R.
Galatola, M.
Cielo, D.
Amoresano, A.
Caterino, M.
De Vita, E.
Illiano, A.
Troncone, R.
Greco, L.
Ruoppolo, M.
A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title_full A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title_fullStr A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title_full_unstemmed A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title_short A Phospholipid Profile at 4 Months Predicts the Onset of Celiac Disease in at-Risk Infants
title_sort phospholipid profile at 4 months predicts the onset of celiac disease in at-risk infants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778072/
https://www.ncbi.nlm.nih.gov/pubmed/31586100
http://dx.doi.org/10.1038/s41598-019-50735-7
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