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

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.

A Controlled Trial of Sheng-Yu-Tang for Post–Hematopoietic Stem Cell Transplantation Leukemia Patients: A Proposed Protocol and Insights From a Preliminary Pilot Study

“…The counts of memory B cells, however, might be low for up to 2 years post-HSCT. 24 Delayed B cell reconstitution has been associated with GVHD, and impaired immunoglobulin gene rearrangement render HSCT patients susceptible to various bacteria and viruses. 25 , 26 …”

Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy

“…We recommend careful assessment of immune reconstitution after lymphodepletion and CAR T cell infusion; the findings should guide decisions regarding antimicrobial prophylaxis and re vaccination 63,128 .…”

Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

“…The impact of IVIG on GVHD has been attributed to the immune-modulatory effects of IVIG. However, it should be noted that utilization of IVIG in the posttransplant period to correct deficiencies in immunoglobulin deficiencies appears to be an accepted use of these preparations in some transplant centers [67][68][69][70][71][72].…”