HLA-B27-homodimer-specific antibody modulates the expansion of pro-inflammatory T-cells in HLA-B27 transgenic rats

10Citations
Citations of this article
39Readers
Mendeley users who have this article in their library.

Abstract

Objectives: HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B27 2) and induce proinflammatory responses that may lead to SpA pathogenesis. The presence of B27 2 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B27 2 -specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods: The monoclonal HD5 antibody was selected from a phage library to target cell-surface B27 2 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B27 2 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results: HD5 bound B27 2 with high specificity and affinity (K d = 0.32 nM). HD5 blocked cell-surface interaction of B27 2 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B27 2 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of proinflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B27 2 molecules. Conclusion: HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B27 2 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

Cite

CITATION STYLE

APA

Belaunzaran, O. M., Kleber, S., Schauer, S., Hausmann, M., Nicholls, F., Van Den Broek, M., … Renner, C. (2015). HLA-B27-homodimer-specific antibody modulates the expansion of pro-inflammatory T-cells in HLA-B27 transgenic rats. PLoS ONE, 10(6). https://doi.org/10.1371/journal.pone.0130811

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free