BAFF is increased in renal transplant patients following treatment with alemtuzumab.
Journal Article (Journal Article)
Alemtuzumab is a monoclonal antibody that depletes T and B cells and is used as induction therapy for renal transplant recipients. Without long-term calcineurin inhibitor (CNI) therapy, alemtuzumab-treated patients have a propensity to develop alloantibody and may undergo antibody-mediated rejection (AMR). In pursuit of a mechanistic explanation, we analyzed peripheral B cells and serum of these patients for BAFF (Blys) and BAFF-R, factors known to be integral for B-cell activation, survival, and homeostasis. Serum BAFF levels of 22/24 alemtuzumab-treated patients were above normal range, with average levels of 1967 pg/mL compared to 775 pg/mL in healthy controls (p = 0.006). BAFF remained elevated 2 years posttransplant in 78% of these patients. BAFF-R on CD19(+) B cells was significantly downregulated, suggesting ligand/receptor engagement. BAFF mRNA expression was increased 2-7-fold in CD14(+) cells of depleted patients, possibly linking monocytes to the BAFF dysregulation. Addition of recombinant BAFF to mixed lymphocyte cultures increased B-cell activation to alloantigen, as measured by CD25 and CD69 coexpression on CD19(+) cells. Of note, addition of sirolimus (SRL) augmented BAFF-enhanced B-cell activation whereas CNIs blocked it. These data suggest associations between BAFF/BAFF-R and AMR in alemtuzumab-treated patients.
Full Text
Duke Authors
Cited Authors
- Bloom, D; Chang, Z; Pauly, K; Kwun, J; Fechner, J; Hayes, C; Samaniego, M; Knechtle, S
Published Date
- August 2009
Published In
Volume / Issue
- 9 / 8
Start / End Page
- 1835 - 1845
PubMed ID
- 19522878
Pubmed Central ID
- PMC4876605
Electronic International Standard Serial Number (EISSN)
- 1600-6143
Digital Object Identifier (DOI)
- 10.1111/j.1600-6143.2009.02710.x
Language
- eng
Conference Location
- United States