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B cells in chronic graft-versus-host disease.

Publication ,  Journal Article
McManigle, W; Youssef, A; Sarantopoulos, S
Published in: Hum Immunol
June 2019

Allogeneic hematopoietic stem cell transplantation (alloHCT) is the definitive therapy for numerous otherwise incurable hematologic malignancies and non-malignant diseases. The genetic disparity between donor and recipient both underpins therapeutic effects and confers donor immune system-mediated damage in the recipient, called graft-versus-host disease (GVHD). Chronic GVHD (cGVHD) is a major cause of late post-transplant morbidity and mortality. B cells have a substantiated role in cGVHD pathogenesis, as first demonstrated by clinical response to the anti-CD20 monoclonal antibody, rituximab. Initiation of CD20 blockade is met at times with limited therapeutic success that has been associated with altered peripheral B cell homeostasis and excess B Cell Activating Factor of the TNF family (BAFF). Increased BAFF to B cell ratios are associated with the presence of circulating, constitutively activated B cells in patients with cGVHD. These cGVHD patient B cells have increased survival capacity and signal through both BAFF-associated and B Cell Receptor (BCR) signaling pathways. Proximal BCR signaling molecules, Syk and BTK, appear to be hyper-activated in cGVHD B cells and can be targeted with small molecule inhibitors. Murine studies have confirmed roles for Syk and BTK in development of cGVHD. Emerging evidence has prompted investigation of several small molecule inhibitors in an attempt to restore B cell homeostasis and potentially target rare, pathologic B cell populations.

Duke Scholars

Published In

Hum Immunol

DOI

EISSN

1879-1166

Publication Date

June 2019

Volume

80

Issue

6

Start / End Page

393 / 399

Location

United States

Related Subject Headings

  • Syk Kinase
  • Signal Transduction
  • Rituximab
  • Receptors, Antigen, B-Cell
  • Mice
  • Immunotherapy
  • Immunology
  • Humans
  • Homeostasis
  • Hematopoietic Stem Cell Transplantation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
McManigle, W., Youssef, A., & Sarantopoulos, S. (2019). B cells in chronic graft-versus-host disease. Hum Immunol, 80(6), 393–399. https://doi.org/10.1016/j.humimm.2019.03.003
McManigle, William, Ayman Youssef, and Stefanie Sarantopoulos. “B cells in chronic graft-versus-host disease.Hum Immunol 80, no. 6 (June 2019): 393–99. https://doi.org/10.1016/j.humimm.2019.03.003.
McManigle W, Youssef A, Sarantopoulos S. B cells in chronic graft-versus-host disease. Hum Immunol. 2019 Jun;80(6):393–9.
McManigle, William, et al. “B cells in chronic graft-versus-host disease.Hum Immunol, vol. 80, no. 6, June 2019, pp. 393–99. Pubmed, doi:10.1016/j.humimm.2019.03.003.
McManigle W, Youssef A, Sarantopoulos S. B cells in chronic graft-versus-host disease. Hum Immunol. 2019 Jun;80(6):393–399.
Journal cover image

Published In

Hum Immunol

DOI

EISSN

1879-1166

Publication Date

June 2019

Volume

80

Issue

6

Start / End Page

393 / 399

Location

United States

Related Subject Headings

  • Syk Kinase
  • Signal Transduction
  • Rituximab
  • Receptors, Antigen, B-Cell
  • Mice
  • Immunotherapy
  • Immunology
  • Humans
  • Homeostasis
  • Hematopoietic Stem Cell Transplantation