title: The role of flow cytometry in celiac disease screening using human leukocyte antigen in adult patients with type 1 diabetes mellitus.
abstract: BACKGROUND
  Patients with type 1 diabetes mellitus (DM1) have an increased risk of celiac disease (CD). Since CD can be seronegative, more sensible tests for detection are needed. In seronegative patients, CD diagnosis may be difficult because of a lack of specificity. Flow cytometry analysis of lymphocyte populations can be useful in this situation. We aimed to study the prevalence of CD in adult DM1 using human leukocyte antigen (HLA) compatibility-based screening. A secondary goal was to study the role of flow cytometry as a complementary tool in these patients.
  
  
  METHODS
  We selected 200 patients with DM1, of whom 190 (95%) had HLA DQ2, DQ8 or both. Of these, 136 agreed to participate and provided epidemiological data. All patients underwent blood tests and gastroscopy.
  
  
  RESULTS
  Sixteen patients had a histology consistent with CD. After ruling out other diagnoses, 6 patients were diagnosed with CD, 2 of whom had negative antibodies. All were DQ2.5 homozygous, with a CD prevalence of 9.8% in this group. In the flow cytometry analysis of duodenal biopsy samples, when we compared all non-CD with CD patients, we found that the γ/δ intraepithelial lymphocyte (IEL) percentage was significantly higher and the CD3 negative IEL percentage significantly lower in the CD group. We found similar results when we compared only those with histological lesions.
  
  
  CONCLUSIONS
  Screening of CD in patients with DM1 by HLA detects only 1% of seronegative patients with CD. DQ2.5 homozygous patients are at most risk of developing CD. The study of lymphocyte populations in the duodenal biopsy by flow cytometry discriminates patients with CD from those without CD with high sensitivity and specificity.
authors.affiliation: Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona (Miren Vicuña Arregui, Jose Manuel Zozaya Urmeneta, Carlos Prieto Martínez).
authors.forename: Miren Vicuña
authors.initials: MV
authors.lastname: Arregui
authors.affiliation: Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona (Miren Vicuña Arregui, Jose Manuel Zozaya Urmeneta, Carlos Prieto Martínez).
authors.forename: Jose Manuel Zozaya
authors.initials: JM
authors.lastname: Urmeneta
authors.affiliation: Department of Gastroenterology, Hospital Reina Sofía, Tudela (Helena León Brito).
authors.forename: Helena León
authors.initials: HL
authors.lastname: Brito
authors.affiliation: Department of Endocrinology and Nutrition, Hospital García Orcoyen, Estella (Juan Pablo Martínez De Esteban).
authors.forename: Juan Pablo Martínez
authors.initials: JP
authors.lastname: De Esteban
authors.affiliation: Department of Gastroenterology, Complejo Hospitalario de Navarra, Pamplona (Miren Vicuña Arregui, Jose Manuel Zozaya Urmeneta, Carlos Prieto Martínez).
authors.forename: Carlos Prieto
authors.initials: CP
authors.lastname: Martínez
authors.affiliation: Department of Endocrinology and Nutrition, Complejo Hospitalario de Navarra, Pamplona (Lluis Forga Llenas).
authors.forename: Lluis Forga
authors.initials: LF
authors.lastname: Llenas
authors.affiliation: Hematology, Complejo Hospitalario de Navarra, Pamplona (Erkuden Aranburu Urtasun, Francisco Sala Pericas).
authors.forename: Erkuden Aranburu
authors.initials: EA
authors.lastname: Urtasun
authors.affiliation: Hematology, Complejo Hospitalario de Navarra, Pamplona (Erkuden Aranburu Urtasun, Francisco Sala Pericas).
authors.forename: Francisco Sala
authors.initials: FS
authors.lastname: Pericas
authors.affiliation: Gastroenterology, Clínica Universidad de Navarra, Pamplona (Ramón Angós Musgo).
authors.forename: Ramón Angós
authors.initials: RA
authors.lastname: Musgo
authors.affiliation: Pathology, Complejo Hospitalario de Navarra, Pamplona (Maria Rosario Mercado Gutierrez).
authors.forename: Maria Rosario Mercado
authors.initials: MR
authors.lastname: Gutierrez
authors.affiliation: Biochemical Laboratory, Complejo Hospitalario de Navarra, Pamplona (Mercedes Palacios Sarrasqueta), Spain.
authors.forename: Mercedes Palacios
authors.initials: MP
authors.lastname: Sarrasqueta
keywords: Celiac disease; HLA typing; flow cytometry; type 1 diabetes mellitus