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Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations
  1. Maria Vicario1,2,3,
  2. Ana M González-Castro1,2,
  3. Cristina Martínez4,
  4. Beatriz Lobo1,2,
  5. Marc Pigrau1,2,
  6. Mar Guilarte5,
  7. Inés de Torres6,
  8. Jose L Mosquera7,
  9. Marina Fortea1,2,
  10. César Sevillano-Aguilera1,2,
  11. Eloisa Salvo-Romero1,2,
  12. Carmen Alonso1,2,3,
  13. Bruno K Rodiño-Janeiro1,2,
  14. Johan D Söderholm8,
  15. Fernando Azpiroz1,2,3,
  16. Javier Santos1,2,3
  1. 1Neuro-immuno-gastroenterology Laboratory, Digestive Diseases Research Unit, Vall d'Hebron Institut de Recerca, Barcelona, Spain
  2. 2Department of Gastroenterology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd)
  4. 4Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany
  5. 5Department of Allergy, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
  6. 6Department of Pathology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain
  7. 7Department of Statistics, University of Barcelona, Barcelona, Spain
  8. 8Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
  1. Correspondence to Dr Maria Vicario, Digestive System Research Unit, Laboratory of Neuro-Immuno-Gastroenterology, Department of Gastroenterology, Vall d'Hebron Institut de Recerca & Hospital Universitario Vall d'Hebron, Paseo Vall d'Hebron 119-129, Barcelona 08035, Spain; maria.vicario{at}vhir.org

Abstract

Background and aims 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.

  • B CELL
  • IRRITABLE BOWEL SYNDROME
  • MUCOSAL IMMUNOLOGY

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