title: Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting of CXCL13 and the BAFF receptor prevents salivary hypofunction.
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.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Buffalo, The State University of New York, Buffalo, NY USA 14214.
authors.forename: Arjun
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Buffalo, The State University of New York, Buffalo, NY USA 14214.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Kiripolsky
authors.affiliation: Vaccinex, Inc., Rochester, NY 14620.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Klimatcheva
authors.affiliation: Vaccinex, Inc., Rochester, NY 14620.
authors.forename: Alan
authors.initials: A
authors.lastname: Howell
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817.
authors.forename: Farzad
authors.initials: F
authors.lastname: Fereidouni
authors.affiliation: Department of Pathology and Laboratory Medicine, UC Davis Medical Center, Sacramento, CA 95817.
authors.forename: Richard
authors.initials: R
authors.lastname: Levenson
authors.affiliation: Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.|Department of Molecular Medicine, School of Medicine, Manhasset, NY 11030.|Department of Medicine, Hofstra North Shore-LIJ, School of Medicine, Manhasset, NY 11030.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Rothstein
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University of Buffalo, The State University of New York, Buffalo, NY USA 14214.|Center for Oncology and Cell Biology, The Feinstein Institute for Medical Research, Manhasset, NY 11030.|Department of Molecular Medicine, School of Medicine, Manhasset, NY 11030.|Department of Dental Medicine, Division of Oral and Maxillofacial Pathology, North Shore-LIJ Health System, Manhasset, NY 11030.
authors.forename: Jill M
authors.initials: JM
authors.lastname: Kramer
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D053265:B-Cell Activation Factor Receptor / Q000037:antagonists & inhibitors / Q000276:immunology; D054382:Chemokine CXCL13 / Q000037:antagonists & inhibitors* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D016688:Mice, Inbred NOD; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000473:pathology / Q000502:physiology; D012793:Sialadenitis / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D012859:Sjogren's Syndrome / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000906:Antibodies; D053265:B-Cell Activation Factor Receptor; D054382:Chemokine CXCL13; C486386:Cxcl13 protein, mouse; C486662:Tnfrsf13c protein, mouse
keywords: Autoantibody; BAFF receptor; CXCL13; Salivary hypofunction; Sialadenitis; Sjögren's syndrome
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