title: HMGB1 as a new biomarker of celiac disease in children: A multicenter study.
abstract: OBJECTIVE
  Despite the availability of specific sierology and point-of-care tests, the phenotypic heterogeneity and the symptoms fluctuation as well as the "open-window" existing among the late and silent forms cause often a delayed celiac disease (CD) diagnosis. Recently, it has been reported that high mobility group box 1 (HMGB1) mediates inflammation and gastrointestinal barrier failure. The aim of this study was to detect serum HMGB1 levels at CD diagnosis and to evaluate the relationship between serum HMGB1 levels and clinical and histologic phenotypes.
  
  
  METHODS
  49 CD children and 44 healthy children were enrolled. Specific antitissue transglutaminase type 2, antideaminated form of gliadin antibodies, serum HMGB1 levels, and typical histopathological changes in duodenal mucosa were performed in all patients. Mucosal lesions were classified according to Marsh classification. In relation to clinical presentation, we classified patients into: typical, atypical and silent forms.
  
  
  RESULTS
  Serum HMGB1 levels were significantly higher in those with CD than those in the healthy control group (P < 0.001). Significant differences in serum HMGB1 levels were detected in children with typical CD form compared to both children with atypical CD form (P < 0.001) and children with silent CD form (P < 0.001). By using the Marsh classification, significant differences were found between subjects with grade 3 B-B1 and 3 C-B2 and villous atrophy, respectively (P < 0.05). On the contrary, no significant differences in serum HMGB1 levels in subgroups of children with grade 3 A compared to grade 3 B-B1 were detected.
  
  
  CONCLUSIONS
  HMGB1 is upregulated at diagnosis in all CD children, especially in typical form, and reflecting the histologic severity of disease.
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Manti
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Cuppari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Tardino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Parisi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Spina
authors.affiliation: Department of Pediatrics, Unit of Pediatric Genetics and Immunology, University of Messina, Messina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Salpietro
authors.affiliation: Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy. Electronic address: Leonardi@unict.it.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Leonardi
mesh_terms: D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood* / Q000175:diagnosis*; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000097:blood; D024243:HMGB1 Protein / Q000097:blood* / Q000235:genetics; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins
keywords: Celiac disease; Disease phenotype; HMGB1; Histologic severity