Plasmablast frequency and trafficking receptor expression are altered in pediatric ulcerative colitis

Inflamm Bowel Dis. 2012 Dec;18(12):2381-91. doi: 10.1002/ibd.22962. Epub 2012 Apr 5.

Abstract

Background: 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.

Methods: 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).

Results: 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 α4β7(high) PBs, and on α4β7(high) /CCR10(high) PBs and MBCs in these patients, consistent with preferential cell targeting to the colon.

Conclusions: 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • B-Lymphocyte Subsets / physiology
  • C-Reactive Protein / analysis
  • Case-Control Studies
  • Child
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / metabolism*
  • Female
  • Flow Cytometry
  • Humans
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Plasma Cells / physiology*
  • Receptors, Lymphocyte Homing / metabolism*
  • Receptors, Lymphocyte Homing / physiology
  • Severity of Illness Index
  • Young Adult

Substances

  • Receptors, Lymphocyte Homing
  • C-Reactive Protein

Supplementary concepts

  • Pediatric ulcerative colitis