Maria Vicario1, Ana M González-Castro2, Cristina Martínez3, Beatriz Lobo2, Marc Pigrau2, Mar Guilarte4, Inés de Torres5, Jose L Mosquera6, Marina Fortea2, César Sevillano-Aguilera2, Eloisa Salvo-Romero2, Carmen Alonso1, Bruno K Rodiño-Janeiro2, Johan D Söderholm7, Fernando Azpiroz1, Javier Santos1. 1. 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). 2. 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. 3. Department of Human Molecular Genetics, Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany. 4. Department of Allergy, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. 5. Department of Pathology, Hospital Universitari Vall d'Hebron & Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain. 6. Department of Statistics, University of Barcelona, Barcelona, Spain. 7. Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Entities:
Keywords:
B CELL; IRRITABLE BOWEL SYNDROME; MUCOSAL IMMUNOLOGY
Authors: Michael Camilleri; Paula Carlson; Nelson Valentin; Andres Acosta; Jessica O'Neill; Deborah Eckert; Roy Dyer; Jie Na; Eric W Klee; Joseph A Murray Journal: Am J Physiol Gastrointest Liver Physiol Date: 2016-07-21 Impact factor: 4.052
Authors: Beatriz Lobo; Laura Ramos; Cristina Martínez; Mar Guilarte; Ana M González-Castro; Carmen Alonso-Cotoner; Marc Pigrau; Inés de Torres; Bruno K Rodiño-Janeiro; Eloisa Salvo-Romero; Marina Fortea; Cristina Pardo-Camacho; Danila Guagnozzi; Fernando Azpiroz; Javier Santos; María Vicario Journal: United European Gastroenterol J Date: 2017-01-29 Impact factor: 4.623