title: Circulating hematopoietic stem cells and putative intestinal stem cells in coeliac disease.
abstract: BACKGROUND
  The intestinal stem cells (ISC) modulation and the role of circulating hematopoietic stem cells (HSC) in coeliac disease (CD) are poorly understood. Our aim was to investigate the longitudinal modifications in peripheral blood HSC traffic and putative ISC density induced by gluten-free diet (GFD) in CD.
  
  
  METHODS
  Thirty-one CD patients and 7 controls were enrolled. Circulating CD133(+) and CD34(+) HSC were measured by flow cytometry, at enrolment and after 7 days and 1, 3, 6, 12, and 24 months of GFD. Endoscopy was performed at diagnosis and repeated at 6, 12, and 24 months following GFD. We used the Marsh-Oberhuber score to evaluate the histological severity of duodenal damage; immunohistochemistry was employed to measure the intraepithelial lymphoid infiltrate (IEL, CD3(+) lymphoid cells) and the putative ISC compartment (CD133(+) and Lgr5(+) epithelial cells).
  
  
  RESULTS
  At enrolment, circulating HSCs were significantly increased in CD patients and they further augmented during the first week of GFD, but progressively decreased afterwards. CD patients presented with villous atrophy, abundant IEL and rare ISC residing at the crypt base. Upon GFD, IEL progressively decreased, while ISC density increased, peaking at 12 months. After 24 months of GFD, all patients were asymptomatic and their duodenal mucosa was macroscopically and histologically normal.
  
  
  CONCLUSIONS
  In active CD patients, the ISC niche is depleted and there is an increased traffic of circulating HSC versus non-coeliac subjects. GFD induces a precocious mobilization of circulating HSC, which is followed by the expansion of the local ISC compartment, leading to mucosal healing and clinical remission.
authors.affiliation: Endoscopy and Gastroenterology Unit, State Hospital, Borgo Maggiore, Republic of San Marino. annachiarapiscaglia@hotmail.com.|Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. annachiarapiscaglia@hotmail.com.
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Piscaglia
authors.affiliation: Division of Translational Medicine, Clinical Research Centre, Sidra Medical and Research Centre, PO Box 26999, Burj Doha, 8th Floor, Doha, Qatar. srutella@sidra.org.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rutella
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. laterza.lucrezia@gmail.com.
authors.forename: Lucrezia
authors.initials: L
authors.lastname: Laterza
authors.affiliation: Endoscopy and Gastroenterology Unit, State Hospital, Borgo Maggiore, Republic of San Marino. valecesario@yahoo.it.|Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. valecesario@yahoo.it.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cesario
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. chiaracampanale@hotmail.com.
authors.forename: Mariachiara
authors.initials: M
authors.lastname: Campanale
authors.affiliation: Endoscopy and Gastroenterology Unit, "S. Caterina Novella" Hospital, Galatina, Lecce, Italy. alessiacazzato@gmail.com.
authors.forename: Immacolata Alessia
authors.initials: IA
authors.lastname: Cazzato
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. jnl_original@hotmail.com.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Ianiro
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. federicobarbaro@hotmail.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Barbaro
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. dimaurizio@yahoo.com.
authors.forename: Luca
authors.initials: L
authors.lastname: Di Maurizio
authors.affiliation: Institute of Gynecology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. giuseppina.bonanno@rm.unicatt.it.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bonanno
authors.affiliation: Institute of Pathology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. tcenci@rm.unicatt.it.
authors.forename: Tonia
authors.initials: T
authors.lastname: Cenci
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. gcammarota@rm.unicatt.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Cammarota
authors.affiliation: Institute of Pathology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. llarocca@rm.unicatt.it.
authors.forename: Luigi Maria
authors.initials: LM
authors.lastname: Larocca
authors.affiliation: Institute of Internal Medicine and Gastroenterology, "A. Gemelli" Hospital, Catholic University, Rome, Italy. agasbarrini@rm.unicatt.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
mesh_terms: D000071916:AC133 Antigen; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D016022:Case-Control Studies; D002446:Celiac Disease / Q000097:blood* / Q000473:pathology*; D002452:Cell Count; D002465:Cell Movement; D055050:Diet, Gluten-Free; D005260:Female; D005500:Follow-Up Studies; D006023:Glycoproteins / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D007422:Intestines / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D055815:Young Adult
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides