Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children: A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution

Hisham Abdel-Azim, Amro Elshoury, Kris M. Mahadeo, Robertson Parkman, Neena Kapoor

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Although T cell immune reconstitution after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been well studied, long-term B cell immune reconstitution remains less characterized. We evaluated humoral immune reconstitution among 71 pediatric allo-HSCT recipients. Although tetanus toxoid antibody levels were normal at 1 year after allo-HSCT, antipolysaccharide carbohydrate antibodies remained persistently low for up to 5 years. While naive B cell counts normalized by 6 months, IgM memory B cell deficiency persisted for up to 2 years (P =.01); switched memory B cell deficiency normalized by 1 year after allo-HSCT. CD4+ T cell immune reconstitution correlated with that of switched memory B cells as early as 6 months after allo-HSCT (r =.55, P =.002) but did not correlate with IgM memory B cells at any time point after allo-HSCT. Taken together, this suggests that allo-HSCT recipients have impaired antibody immune reconstitution, mainly due to IgM memory B cell maturation block, compared with more prompt T cell–dependent switched memory cell immune reconstitution. We further explored other factors that might affect humoral immune reconstitution. The use of total body irradiation was associated with lower naive B cells counts at 6 months after HSCT (P =.04) and lower IgM (P =.008) and switched (P =.003) memory B cells up to 2 years. Allo-HSCT recipients with extensive chronic graft-versus-host disease had lower IgM memory B cell counts (P =.03) up to 2 years after allo-HSCT. The use of cord blood was associated with better naive (P =.01), IgM (P =.0005), and switched memory (P =.006) B cells immune reconstitution. These findings may inform future prophylaxis and treatment strategies regarding risk of overwhelming infection, graft-versus-host disease, and post-allogeneic HSCT revaccination.

Original languageEnglish (US)
Pages (from-to)1437-1446
Number of pages10
JournalBiology of Blood and Marrow Transplantation
Volume23
Issue number9
DOIs
StatePublished - Sep 2017

Keywords

  • Allogeneic transplantation
  • B cell
  • Children
  • Humoral
  • Immune reconstitution

ASJC Scopus subject areas

  • Hematology
  • Transplantation

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