B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation.

Journal Article (Clinical Trial;Journal Article)

Allogeneic hematopoietic stem cell transplant (HSCT) typically results in donor T-cell engraftment and function in patients with severe combined immunodeficiency (SCID), but humoral immunity, particularly when using donors other than matched siblings, is variable. B-cell function after HSCT for SCID depends on the genetic cause, the use of pre-HSCT conditioning, and whether donor B-cell chimerism is achieved. Patients with defects in IL2RG or JAK3 undergoing HSCT without conditioning often have poor B-cell function post-HSCT, perhaps as a result of impairment of IL-21 signaling in host-derived B cells. To investigate the effect of pre-HSCT conditioning on B-cell function, and the relationship of in vitro B-cell function to clinical humoral immune status, we analyzed 48 patients with IL2RG/JAK3 SCID who were older than 2 years after HSCT with donors other than matched siblings. T follicular helper cells (TFH) developed in these patients with kinetics similar to healthy young children; thus, poor B-cell function could not be attributed to a failure of TFH development. In vitro differentiation of B cells into plasmablasts and immunoglobulin secretion in response to IL-21 strongly correlated with the use of conditioning, donor B-cell engraftment, freedom from immunoglobulin replacement, and response to tetanus vaccine. Patients receiving immunoglobulin replacement who had normal serum immunoglobulin M showed poor response to IL-21 in vitro, similar to those with low serum IgM. In vitro response of B cells to IL-21 may predict clinically relevant humoral immune function in patients with IL2RG/JAK3 SCID after HSCT.

Full Text

Duke Authors

Cited Authors

  • Miggelbrink, AM; Logan, BR; Buckley, RH; Parrott, RE; Dvorak, CC; Kapoor, N; Abdel-Azim, H; Prockop, SE; Shyr, D; Decaluwe, H; Hanson, IC; Gillio, A; Dávila Saldaña, BJ; Eibel, H; Hopkins, G; Walter, JE; Whangbo, JS; Kohn, DB; Puck, JM; Cowan, MJ; Griffith, LM; Haddad, E; O'Reilly, RJ; Notarangelo, LD; Pai, S-Y

Published Date

  • June 28, 2018

Published In

Volume / Issue

  • 131 / 26

Start / End Page

  • 2967 - 2977

PubMed ID

  • 29728406

Pubmed Central ID

  • PMC6024640

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

Digital Object Identifier (DOI)

  • 10.1182/blood-2017-10-809822


  • eng

Conference Location

  • United States