title: Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations.
abstract: OBJECTIVE
  Altered intestinal barrier is associated with immune activation and clinical symptoms in diarrhoea-predominant IBS (IBS-D). Increased mucosal antigen load may induce specific responses; however, local antibody production and its contribution to IBS aetiopathogenesis remain undefined. This study evaluated the role of humoral activity in IBS-D.
  
  
  METHODS
  A single mucosal jejunal biopsy, luminal content and blood were obtained from healthy volunteers (H; n=30) and IBS-D (n=49; Rome III criteria) participants. Intraepithelial lymphocytes, mast cells, B lymphocytes and plasma cells were studied by imaging techniques. Differential gene expression and pathway analysis were assessed by microarray and PCR techniques. Blood and luminal immunoglobulins (Igs) were quantified. Gastrointestinal symptoms, respiratory atopy and stress and depression were also recorded.
  
  
  RESULTS
  Patients with IBS-D showed a higher number and activation of mucosal B lymphocytes and plasma cells (p<0.05). Mast cell density was increased in patients with IBS-D (non-atopic) and in close proximity to plasma cells (p<0.05). Microarray profiling identified differential humoral activity in IBS-D, involving proliferation and activation of B lymphocytes and Igs production (p<0.001). Mucosal humoral activity was higher in IBS-D, with upregulation of germline transcripts and Ig genes (1.3-fold-1.7-fold increase; p<0.05), and increased IgG(+) cells and luminal IgG compared with H (p<0.05), with no differences in blood. Biological markers of humoral activity correlated positively with bowel movements, stool form and depression.
  
  
  CONCLUSIONS
  Enhanced small bowel humoral immunity is a distinctive feature of IBS-D. Mucosal Ig production contributes to local inflammation and clinical manifestations in IBS-D.
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
authors.forename: Maria
authors.initials: M
authors.lastname: Vicario
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: González-Castro
authors.affiliation: Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Martínez
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Lobo
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marc
authors.initials: M
authors.lastname: Pigrau
authors.affiliation: Department of Allergy, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Guilarte
authors.affiliation: Department of Pathology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Inés
authors.initials: I
authors.lastname: de Torres
authors.affiliation: Department of Statistics, University of Barcelona, Barcelona, Spain.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Mosquera
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Fortea
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: César
authors.initials: C
authors.lastname: Sevillano-Aguilera
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Salvo-Romero
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
authors.forename: Carmen
authors.initials: C
authors.lastname: Alonso
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Bruno K
authors.initials: BK
authors.lastname: Rodiño-Janeiro
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
authors.forename: Johan D
authors.initials: JD
authors.lastname: Söderholm
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
authors.forename: Fernando
authors.initials: F
authors.lastname: Azpiroz
authors.affiliation: Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd).
authors.forename: Javier
authors.initials: J
authors.lastname: Santos
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001707:Biopsy, Needle; D016022:Case-Control Studies; D003967:Diarrhea / Q000276:immunology / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D056724:Immunity, Humoral / Q000276:immunology*; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000276:immunology* / Q000473:pathology; D043183:Irritable Bowel Syndrome / Q000276:immunology* / Q000503:physiopathology*; D007583:Jejunum / Q000276:immunology / Q000473:pathology*; D008297:Male; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D007136:Immunoglobulins
keywords: B CELL; IRRITABLE BOWEL SYNDROME; MUCOSAL IMMUNOLOGY