title: Evolution of nonspecific duodenal lymphocytosis over 2 years of follow-up.
abstract: OBJECTIVE
  To assess the evolution of duodenal lymphocytosis (DL), a condition characterized by increased intraepithelial lymphocytes (IELs), over 2 years of follow-up.
  
  
  METHODS
  Consecutive patients undergoing upper endoscopy/histology for abdominal pain, diarrhea, weight loss, weakness or other extraintestinal features compatible with celiac disease (CD) were included. Evaluation of IELs infiltrate in duodenal biopsy samples was carried out by CD3-immunohistochemistry and expressed as number of positive cells/100 enterocytes. Diagnostic agreement on the IELs count was tested by calculating the weighted k coefficient. All patients underwent serological detection of autoantibodies associated with CD: IgG and IgA anti-tissue transglutaminase and endomysium. Each patient underwent further investigations to clarify the origin of DL at baseline and/or in the course of 2 years of follow-up every six months. Autoimmune thyroiditis, intestinal infections, parasitic diseases, bacterial intestinal overgrowth, hypolactasia and wheat allergy were detected. Colonoscopy and enteric magnetic resonance imaging were performed when necessary. Risk factors affecting the final diagnosis were detected by multinomial logistic regression and expressed as OR.
  
  
  RESULTS
  Eighty-five patients (16 males, 69 females, aged 34.1 ± 12.5 years) were followed up for a mean period of 21.7 ± 11.7 mo. At baseline, endoscopy/duodenal biopsy, CD3 immunohistochemistry revealed: > 25 IELs/100 enterocytes in 22 subjects, 15-25 IELs in 37 and < 15 IELs in 26. They all had negative serum anti-transglutaminase and anti-endomysium, whilst 5 showed IgG anti-gliadin positivity. In the course of follow-up, 23 developed CD seropositivity and gluten sensitivity (GS) was identified in 19. Other diagnoses were: 5 Helicobacter pylori infections, 4 jejunal Crohn's disease, 1 lymphocytic colitis and 1 systemic sclerosis. The disease in the remaining 32 patients was classified as irritable bowel syndrome because of the lack of diagnostic evidence. At multivariate analysis, the evolution towards CD was associated with an IELs infiltrate > 25 (OR = 1640.4) or 15-25 (OR = 16.95), human leukocyte antigen (HLA) DQ2/8 (OR = 140.85) or DQA1*0501 (OR = 15.36), diarrhea (OR = 5.56) and weakness (OR = 11.57). GS was associated with IELs 15-25 (OR = 28.59), autoimmune thyroiditis (OR = 87.63), folate deficiency (OR = 48.53) and diarrhea (OR = 54.87).
  
  
  CONCLUSIONS
  DL may have a multifactorial origin but the IELs infiltrate and HLA are strong predictive factors for CD development and a clinical diagnosis of GS.
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Losurdo
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Piscitelli
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giangaspero
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Mariabeatrice
authors.initials: M
authors.lastname: Principi
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Buffelli
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Floriana
authors.initials: F
authors.lastname: Giorgio
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Montenegro
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Sorrentino
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Annacinzia
authors.initials: A
authors.lastname: Amoruso
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Ierardi
authors.affiliation: Giuseppe Losurdo, Domenico Piscitelli, Antonio Giangaspero, Mariabeatrice Principi, Francesca Buffelli, Floriana Giorgio, Lucia Montenegro, Claudia Sorrentino, Annacinzia Amoruso, Enzo Ierardi, Alfredo Di Leo, Gastroenterology Section, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Di Leo
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D015415:Biomarkers / Q000032:analysis; D001706:Biopsy; D017252:CD3 Complex / Q000032:analysis; D002446:Celiac Disease / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D016009:Chi-Square Distribution; D003113:Colonoscopy; D018450:Disease Progression; D004378:Duodenal Diseases / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D004384:Duodenoscopy; D004386:Duodenum / Q000276:immunology / Q000473:pathology*; D005260:Female; D005500:Follow-Up Studies; D005512:Food Hypersensitivity / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D005983:Glutens / Q000009:adverse effects* / Q000276:immunology; D006680:HLA Antigens / Q000032:analysis; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology*; D016015:Logistic Models; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology*; D008218:Lymphocytosis / Q000175:diagnosis* / Q000276:immunology / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D017252:CD3 Complex; D006680:HLA Antigens; D005983:Glutens
keywords: Celiac disease; Duodenal lymphocytosis; Gluten sensitivity; Immunohistochemistry; Intraepithelial lymphocytes; Seronegative celiac disease