Faculty Collaboration Database

B-cell differentiation and IL-21 response in IL2RG/JAK3 SCID patients after hematopoietic stem cell transplantation. Blood 2018 Jun 28;131(26):2967-2977

Date

05/08/2018

Pubmed ID

29728406

Pubmed Central ID

PMC6024640

DOI

10.1182/blood-2017-10-809822

Scopus ID

2-s2.0-85049141956 (requires institutional sign-in at Scopus site)   33 Citations

Abstract

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 (T_FH) developed in these patients with kinetics similar to healthy young children; thus, poor B-cell function could not be attributed to a failure of T_FH 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.

Author List

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 SY

Author

Brent R. Logan PhD Director, Professor in the Institute for Health and Equity department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
B-Lymphocytes
Cell Differentiation
Child
Child, Preschool
Female
Hematopoietic Stem Cell Transplantation
Humans
Immunity, Humoral
Interleukin Receptor Common gamma Subunit
Interleukins
Janus Kinase 3
Lymphocyte Activation
Male
Severe Combined Immunodeficiency
T-Lymphocytes
Transplantation Conditioning
Transplantation, Homologous
Young Adult