The last two authors are cosenior authors for this study; both directed this study.
Plasmablast frequency and trafficking receptor expression are altered in pediatric ulcerative colitis
Article first published online: 5 APR 2012
Copyright © 2012 Crohn's & Colitis Foundation of America, Inc.
Inflammatory Bowel Diseases
Volume 18, Issue 12, pages 2381–2391, December 2012
How to Cite
Tarlton, N. J., Green, C. M., Lazarus, N. H., Rott, L., Wong, A. P., Abramson, O. N., Bremer, M., Butcher, E. C. and Abramson, T. (2012), Plasmablast frequency and trafficking receptor expression are altered in pediatric ulcerative colitis. Inflamm Bowel Dis, 18: 2381–2391. doi: 10.1002/ibd.22962
- Issue published online: 15 NOV 2012
- Article first published online: 5 APR 2012
- Manuscript Accepted: 5 MAR 2012
- Manuscript Received: 19 FEB 2012
- NIH. Grant Numbers: R37 AI047822, U19 AI090019, RC1 AI087257
- Gates Foundation
- inflammatory bowel disease;
- memory B cell;
- trafficking receptor;
- ulcerative colitis
The incidence of pediatric ulcerative colitis (UC), a chronic autoinflammatory disease of the colon, is on the rise. Although an increased infiltration of B cells from the peripheral blood into the colon occurs in UC, B-cell trafficking is understudied. We hypothesized that the frequency of circulating plasmablasts (PBs) and their trafficking receptor (TR) expression may be indicative of the location and degree of pathology in pediatric UC.
We conducted multicolor flow cytometry analyses of circulating IgA+/− PBs and IgA+ memory B cells (MBCs) in pediatric UC patients with remission, mild, moderate, and severe state of disease (n = 12), and healthy pediatric (n = 2) and adult donors (n = 11).
Compared to healthy donors the average frequency of PBs among total peripheral blood lymphocytes is increased 30-fold during severe UC activity, and positively correlates with Pediatric Ulcerative Colitis Activity Index score, C-reactive protein level, and erythrocyte sedimentation rate. A greater percent of PBs in severe patients express the gut-homing receptors α4β7 and CCR10, and the inflammatory homing molecule P-selectin ligand (P-sel lig). The percent of IgA+ MBCs expressing α4β7, however, is reduced. Furthermore, expression of the small intestine TR CCR9 is decreased on α4β7high PBs, and on α4β7high/CCR10high PBs and MBCs in these patients, consistent with preferential cell targeting to the colon.
Peripheral blood PBs with a colon-homing phenotype (α4β7/CCR10/P-sel lig) are elevated in children with severe UC. Screening this B-cell subset may provide a complementary approach in monitoring disease activity or therapeutic efficacy in pediatric UC. (Inflamm Bowel Dis 2012;)