title: Seronegative celiac disease: Shedding light on an obscure clinical entity.
abstract: BACKGROUND
  Although serological tests are useful for identifying celiac disease, it is well established that a minority of celiacs are seronegative.
  
  
  OBJECTIVE
  To define the prevalence and features of seronegative compared to seropositive celiac disease, and to establish whether celiac disease is a common cause of seronegative villous atrophy.
  
  
  METHODS
  Starting from 810 celiac disease diagnoses, seronegative patients were retrospectively characterized for clinical, histological and laboratory findings.
  
  
  RESULTS
  Of the 810 patients, fourteen fulfilled the diagnostic criteria for seronegative celiac disease based on antibody negativity, villous atrophy, HLA-DQ2/-DQ8 positivity and clinical/histological improvement after gluten free diet. Compared to seropositive, seronegative celiac disease showed a significantly higher median age at diagnosis and a higher prevalence of classical phenotype (i.e., malabsorption), autoimmune disorders and severe villous atrophy. The most frequent diagnosis in the 31 cases with seronegative flat mucosa was celiac disease (45%), whereas other diagnoses were Giardiasis (20%), common variable immunodeficiency (16%) and autoimmune enteropathy (10%).
  
  
  CONCLUSIONS
  Although rare seronegative celiac disease can be regarded as the most frequent cause of seronegative villous atrophy being characterized by a high median age at diagnosis; a close association with malabsorption and flat mucosa; and a high prevalence of autoimmune disorders.
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Volta
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Caio
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Boschetti
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Giancola
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Kerry J
authors.initials: KJ
authors.lastname: Rhoden
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Eugenio
authors.initials: E
authors.lastname: Ruggeri
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Paterini
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna, St. Orsola-Malpighi Hospital, Italy. Electronic address: roberto.degiorgio@unibo.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: De Giorgio
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D001323:Autoantibodies / Q000097:blood*; D002446:Celiac Disease / Q000097:blood* / Q000175:diagnosis*; D017074:Common Variable Immunodeficiency / Q000453:epidemiology; D055050:Diet, Gluten-Free; D005260:Female; D005873:Giardiasis / Q000453:epidemiology; D006683:HLA-DQ Antigens / Q000276:immunology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology*; D007558:Italy; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology; D012189:Retrospective Studies; D016036:Seroepidemiologic Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; C109756:HLA-DQ8 antigen
keywords: Autoantibodies; Autoimmune disorders; Autoimmune enteropathy; Common variable immunodeficiency; Olmesartan; Seronegative celiac disease; Villous atrophy