title: Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients.
abstract: OBJECTIVE
  Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring.
  
  
  METHODS
  We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously.
  
  
  RESULTS
  Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP.
  
  
  CONCLUSIONS
  Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397.
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Comino
authors.affiliation: Department of Gastroenterology, Hospital Universitari Mutua Terrassa, and CIBERehd, Terrassa, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Bañares
authors.affiliation: Department of Gastroenterology, Hospital Universitari Mutua Terrassa, and CIBERehd, Terrassa, Barcelona, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Esteve
authors.affiliation: Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de La Candelaria, Tenerife, Spain.
authors.forename: Luís
authors.initials: L
authors.lastname: Ortigosa
authors.affiliation: Pediatric Gastroenterology, Hospital Universitari de Sant Joan de Reus, IISPV, URV, Reus, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castillejo
authors.affiliation: Unit for the Clinical Management of Digestive Diseases and CIBERehd and Gastroenterology and Nutrition Unit, Hospital Universitario Virgen de Valme, Seville, Spain.
authors.forename: Blanca
authors.initials: B
authors.lastname: Fambuena
authors.affiliation: Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario y Politécnico La Fe, Celiac Disease and Digestive Inmunopatology Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Ribes-Koninckx
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Hospital Materno-Infantil, Malaga, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sierra
authors.affiliation: Gastroenterology and Nutrition Unit, Instituto Hispalense de Pediatría, Seville, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Rodríguez-Herrera
authors.affiliation: Servicio de Gastroenterología Pediátrica, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Salazar
authors.affiliation: Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Caunedo
authors.affiliation: Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, CSIC and Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: J M
authors.initials: JM
authors.lastname: Marugán-Miguelsanz
authors.affiliation: Clinical Analysis and Pediatrics, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: José Antonio
authors.initials: JA
authors.lastname: Garrote
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario de Leon, Leon, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Vivas
authors.affiliation: Sección de Aparato Digestivo, Hospital del Tajo, Madrid, Spain.
authors.forename: Oreste
authors.initials: O
authors.lastname: Lo Iacono
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario de Leon, Leon, Spain.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Nuñez
authors.affiliation: Servicio de Aparato Digestivo, Hospital Universitario de Leon, Leon, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Vaquero
authors.affiliation: Clinical Analysis and Pediatrics, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: Ana María
authors.initials: AM
authors.lastname: Vegas
authors.affiliation: Clinical Analysis and Pediatrics, Hospital Universitario Río Hortega, Valladolid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Crespo
authors.affiliation: Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, CSIC and Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Fernández-Salazar
authors.affiliation: Mucosal Immunology Laboratory, Instituto de Biología y Genética Molecular (IBGM), University of Valladolid, CSIC and Gastroenterology Unit, Hospital Clínico Universitario de Valladolid, Valladolid, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Arranz
authors.affiliation: Hospital Universitario Virgen Macarena, Seville, Spain.
authors.forename: Victoria Alejandra
authors.initials: VA
authors.lastname: Jiménez-García
authors.affiliation: Servicio de Inmunología, CIBER de Epidemiología y Salud Pública, Hospital Universitario Virgen del Rocío/IBiS/CSIC/Universidad de Sevilla, Seville, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Antonio Montes-Cano
authors.affiliation: Servicio de Gastroenterología Pediátrica, Hospital Universitario Virgen del Rocío, Seville, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Espín
authors.affiliation: Gastroenterology and Nutrition Unit, Instituto Hispalense de Pediatría, Seville, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Galera
authors.affiliation: Gastroenterology and Nutrition Unit, Instituto Hispalense de Pediatría, Seville, Spain.
authors.forename: Justo
authors.initials: J
authors.lastname: Valverde
authors.affiliation: Pediatric Gastroenterology and Nutrition Unit, Hospital Materno-Infantil, Malaga, Spain.
authors.forename: Francisco José
authors.initials: FJ
authors.lastname: Girón
authors.affiliation: Pediatric Gastroenterology, Hepatology and Nutrition Unit, Hospital Universitario y Politécnico La Fe, Celiac Disease and Digestive Inmunopatology Unit, Instituto de Investigación Sanitaria La Fe, Valencia, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Bolonio
authors.affiliation: Unit for the Clinical Management of Digestive Diseases and CIBERehd and Gastroenterology and Nutrition Unit, Hospital Universitario Virgen de Valme, Seville, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Millán
authors.affiliation: Pediatric Gastroenterology, Hospital Universitari de Sant Joan de Reus, IISPV, URV, Reus, Spain.
authors.forename: Francesc Martínez
authors.initials: FM
authors.lastname: Cerezo
authors.affiliation: Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de La Candelaria, Tenerife, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Guajardo
authors.affiliation: Pediatric Gastroenterology, Hospital Universitario Nuestra Señora de La Candelaria, Tenerife, Spain.
authors.forename: José Ramón
authors.initials: JR
authors.lastname: Alberto
authors.affiliation: Department of Gastroenterology, Hospital Universitari Mutua Terrassa, and CIBERehd, Terrassa, Barcelona, Spain.
authors.forename: Mercé
authors.initials: M
authors.lastname: Rosinach
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Segura
authors.affiliation: Celimmune, Bethesda, Maryland, USA.
authors.forename: Francisco
authors.initials: F
authors.lastname: León
authors.affiliation: Biomedal SL, Seville, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Marinich
authors.affiliation: Biomedal SL, Seville, Spain.
authors.forename: Alba
authors.initials: A
authors.lastname: Muñoz-Suano
authors.affiliation: Unit for the Clinical Management of Digestive Diseases and CIBERehd and Gastroenterology and Nutrition Unit, Hospital Universitario Virgen de Valme, Seville, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Romero-Gómez
authors.affiliation: Biomedal SL, Seville, Spain.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Cebolla
authors.affiliation: Department of Microbiology and Parasitology, Faculty of Pharmacy, University of Seville, Seville, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sousa
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000906:Antibodies / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000178:diet therapy* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D015930:Diet Records; D055050:Diet, Gluten-Free; D004797:Enzyme-Linked Immunosorbent Assay; D005243:Feces / Q000737:chemistry*; D005260:Female; D019204:GTP-Binding Proteins / Q000276:immunology*; D005903:Gliadin / Q000276:immunology*; D005983:Glutens / Q000032:analysis*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007223:Infant; D008297:Male; D010349:Patient Compliance; D011446:Prospective Studies; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D012698:Serologic Tests; D011795:Surveys and Questionnaires; D011503:Transglutaminases / Q000276:immunology*; D055815:Young Adult
chemical_list: D000906:Antibodies; D001323:Autoantibodies; D007070:Immunoglobulin A; D005983:Glutens; D005903:Gliadin; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins