TY - JOUR
T1 - Humoral Immune Reconstitution Kinetics after Allogeneic Hematopoietic Stem Cell Transplantation in Children
T2 - A Maturation Block of IgM Memory B Cells May Lead to Impaired Antibody Immune Reconstitution
AU - Abdel-Azim, Hisham
AU - Elshoury, Amro
AU - Mahadeo, Kris M.
AU - Parkman, Robertson
AU - Kapoor, Neena
N1 - Publisher Copyright:
© 2017 The American Society for Blood and Marrow Transplantation
PY - 2017/9
Y1 - 2017/9
N2 - 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.
AB - 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.
KW - Allogeneic transplantation
KW - B cell
KW - Children
KW - Humoral
KW - Immune reconstitution
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U2 - 10.1016/j.bbmt.2017.05.005
DO - 10.1016/j.bbmt.2017.05.005
M3 - Article
AN - SCOPUS:85021279873
VL - 23
SP - 1437
EP - 1446
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
SN - 1083-8791
IS - 9
ER -