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Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunct... - PubMed - NCBI
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Clin Immunol. 2016 Mar;164:85-94. doi: 10.1016/j.clim.2016.01.015. Epub 2016 Jan 28.

Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction.

Author information

1
Department of Oral Biology, School of Dental Medicine, University of Buffalo, The State University of New York, Buffalo, NY USA 14214.
2
Vaccinex, Inc., Rochester, NY 14620.
3
Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817.
4
Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.
5
Department of Molecular Medicine, School of Medicine, Manhasset, NY 11030.
6
Department of Medicine, Hofstra North Shore-LIJ, School of Medicine, Manhasset, NY 11030.
7
Department of Dental Medicine, Division of Oral and Maxillofacial Pathology, North Shore-LIJ Health System, Manhasset, NY 11030.
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Contributed equally

Abstract

Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS.

KEYWORDS:

Autoantibody; BAFF receptor; CXCL13; Salivary hypofunction; Sialadenitis; Sjögren's syndrome

PMID:
26826598
PMCID:
PMC4780410
[Available on 2017-03-01]
DOI:
10.1016/j.clim.2016.01.015
[Indexed for MEDLINE]
Free PMC Article
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