P086 Identification of constitutive modifications in plasma cells and B lymphocytes in patients with inflammatory bowel disease
A.C. Marin1, S. Fernández-Tomé1, L. Ortega Moreno2, V. Martin Dominguez3, S. Casabona3, I. Becerro3, I. Mora-Gutiérrez1, I. Villacañas-Gil1, M. Baldan-Martin1, J.A. Moreno-Monteagudo3, C. Santander2, M. Chaparro2, D. Bernardo1,4,5, J.P. Gisbert2,5
1Hospital Universitario de La Princesa, Department of Gastroenterology, IIS-IP and CIBERehd, Madrid, Spain, 2Hospital Universitario de La Princesa, Department of Gastroenterology, IIS-IP and CIBERehd. Departamento de Medicina. Universidad Autónoma de Madrid., Madrid, Spain, 3Hospital Universitario de La Princesa, Department of Gastroenterology, IIS-IP, Madrid, Spain, 4Instituto de Biología y Genética Molecular IBGM, Mucosal Immunology Lab. Universidad de Valladolid-CSIC., Valladolid, Spain, 5Both authors had equal contribution, as senior authors, Madrid, Spain
Background
Plasma cells (PCs) and B lymphocytes (BLs) are a source of immunoglobulins (Ig), being IgA essential for intestinal homeostasis. An unbalanced intestinal Ig production has been described in inflammatory bowel disease (IBD). Nevertheless little is known about the role of mucosal Ig-producing BL and PC in IBD, reason why we decided to study them.
Methods
We included 12 healthy controls -HC-, 10 patients with ulcerative colitis (three active -aUC- and seven quiescent -qUC) and 10 patients with Crohn’s disease (three active -aCD- and seven quiescent -qCD). Disease was located in the distal colon in all patients, although the quiescent ones had no inflammation (endoscopic Mayo = 0; SES-CD = 0–1). Distal colon biopsies were collected together with peripheral blood. Mucus layer and epithelial barrier was removed from the biopsies and lamina propria mononuclear cells were harvested using the ‘walk-out’ protocol. Peripheral blood mononuclear cells were obtained after ficoll centrifugation. In both cases, cells were stained with specific antibodies, acquired in a FACSCanto II cytometer, and analysed with FlowJo. Median percentage of PC and BL (and their subsets) relative to each tissue was calculated and compared using non-parametric statistics, considering statistically significant
Results
The proportion of plasmablasts, blood-precursors of PC, was higher in the blood of active IBD patients (HC: 0.8%; aUC: 5.3%; aCD: 3.4%). Even though there were no differences in the colonic proportion of PC between the study groups, there was a constitutive lower proportion of IgA-producing PC in IBD, irrespective of its type (UC or CD) or presence of inflammation (HC: 88%; qUC: 55%; aUC: 38%; qCD: 70%; aCD: 44%). Moreover, aCD patients also showed a significantly higher proportion of IgM-producing PC (HC: 6% vs. aCD: 10%), and a higher proportion PC expressing CD19 compared both with HC and qCD (HC: 43%; qCD: 52%; aCD: 74%). The proportion of BL and their subsets did not show differences between the study groups, neither in blood nor in colon. However, in UC patients, some circulating subsets displayed a lower proportion of cells expressing the gut-homing integrin β7: naive BL (HC: 11.5%; qUC: 2.9%; aUC: 0.6%) and IgM memory BL type CD27+ (HC: 43%; qUC: 30%; aUC: 23%) and also CD27- (HC: 32% vs. aUC: 5%).
Conclusion
IBD patients have a diminished percentage of colonic IgA-producing PC, which is irrespective of the type of IBD or the inflammatory status; this reduction could compromise the correct microbiota regulation in IBD. The reduction of the percentage of β7-expressing BL in the blood of UC patients could potentially point to a specific pathogenic mechanism of UC.