Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations
2015 (English)In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 64, no 9, 1379-1388 p.Article in journal (Refereed) Published
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 less than 0.05). Mast cell density was increased in patients with IBS-D (non-atopic) and in close proximity to plasma cells (p less than 0.05). Microarray profiling identified differential humoral activity in IBS-D, involving proliferation and activation of B lymphocytes and Igs production (p less than 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 less than 0.05), and increased IgG(+) cells and luminal IgG compared with H (p less than 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.
Place, publisher, year, edition, pages
BMJ PUBLISHING GROUP , 2015. Vol. 64, no 9, 1379-1388 p.
IdentifiersURN: urn:nbn:se:liu:diva-121427DOI: 10.1136/gutjnl-2013-306236ISI: 000360389800006PubMedID: 25209656OAI: oai:DiVA.org:liu-121427DiVA: diva2:855136
Funding Agencies|Fondo de Investigacion Sanitaria; CIBERehd, Instituto de Salud Carlos III, Subdireccion General de Investigacion Sanitaria, Ministerio de Economia y Competitividad [CP10/00502, PI13/00935, CM08/00229, CM10/00155, FI12/00254, PI12/00314, EII2011-0035, PI11/00716]; Ministerio de Educacion, Direccion General de Investigacion [SAF 2009-07416]; Agencia de Gestio dAjuts Universitaris i de Recerca, de la Generalitat de Catalunya [2009 SGR 219, 2011 BP/A00099]; Rome Foundation; Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas [CB06/04/0021]2015-09-182015-09-182015-09-28Bibliographically approved